Yourlawyer.com (Vytorin News)

Vytorin, Zetia Disappoint Again

Mon, 16 Nov 2009 00:00:00 -0800

Vytorin and Zetia, Merck & Co.'s anti-cholesterol medications, are coming under fire again. A new study has found that a much older - and cheaper - drug reduced artery plaque much better in eight months than ezetimibe, the active ingredient in both Vytorin and Zetia.

According to USA Today, this latest study was released Sunday at an American Heart Association meeting and published online by the New England Journal of Medicine.

Vytorin, developed and marketed jointly by Merck and Schering-Plough, is a combination of cholesterol-lowering Zetia and the statin Zocor. Vytorin was approved by the Food & Drug Administration in 2004 to treat both sources of cholesterol – absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues. It was believed that the treatment of cholesterol from both sources would likely result in lower cholesterol levels. It was likewise theorized that this reduction in cholesterol would in turn reduce the amount of plaque buildup in the arteries, thus reducing the risk of heart attack and stroke.

According to USA Today, the latest Vytorin and Zetia study compared ezetimibe with prescription Niaspan, made by Abbott Laboratories. Niaspan is a slow-release form of niacin, a drug which has been around for 50 years. The Abbott-sponsored study involved 363 patients who had heart disease or a high risk of heart problems. All had been taking statins and had relatively low levels of bad cholesterol. Half of the patients were given Niaspan, and half were given Zetia, USA Today said.

The study found that Niaspan reduced plaque in neck arteries by 2%,while Zetia did not. Two people in the Niaspan group had heart attacks or other major cardiac events, compared with nine in the Zetia group.

While the study did have some limitations, - a small size, and the fact that it was stopped after 14 months because patients in the niacin group were doing better - it is not the first to question the supposed benefits of Vytorin and Zetia. The drugs have been the subject of controversy since the ENHANCE study was released in January 2008. ENHANCE found that the Vytorin was no better than a cheaper, generic statin in preventing clogged arteries, and raised serious questions about the effectiveness of both Vytorin and Zetia. What’s more, Merck and Schering-Plough delayed releasing ENHANCE for more than a year, even though the trial was actually completed in 2006.

The ENHANCE controversy spawned scores of lawsuits against Merck and Schering-Plough. Many accused the companies of marketing Vytorin and Zetia in a misleading fashion and failing to disclose the results of ENHANCE in a timely manner. Earlier this year, Merck and Schering-Plough agreed to pay $41.5 million to settle class-action lawsuits stemming from that debacle.

Lawsuit Claims Execs Knew Vytorin Study Wouldn't Be Favorable

Thu, 15 Oct 2009 00:00:00 -0700

A lawsuit alleges that marketing executives at Schering-Plough, one of the makers of Vytorin, knew long before it was released that the ENHANCE study would not be favorable.

Vytorin is a combination of Zetia and the statin Zocor that is marketed jointly by Merck & Co. and Schering-Plough. It has been under the microscope since the ENHANCE study was released, showing it was no better at preventing clogged arteries than a cheaper statin. ENHANCE raised serious questions about the effectiveness of both Vytorin and Zetia.

The ENHANCE debacle spawned scores of lawsuits against Merck and Schering-Plough. Many accused the companies of marketing Vytorin and Zetia in a misleading fashion and failing to disclose the results of ENHANCE in a timely manner. In August, the drug makers agreed to pay $41.5 million to settle class-action lawsuits filed by consumers who used Vytorin and Zetia.

Rumors have swirled ever since the ENHANCE release that Merck and Schering-Plough had known that the study would be disappointing long before the release. For example, in February 2008, we reported that Congressional investigators were looking into some incriminating comments posted on Cafepharma.com by anonymous pharmaceutical sales reps that indicated prior knowledge of the ENHANCE findings. The author of one March 2007 comment claimed to have a “buddy” at Schering-Plough. “He says that the study is a bust,” the post stated. Another post in 2007 stated, “Heard it crashed and burned!” A third, detailed post about the study stated, “Adding Zetia to high dose generic statin provides no real benefit."

Now, Fierce Pharma is reporting that a lawsuit filed on behalf of pension plan investors has been amended to include more detailed allegations that Schering-Plough executives had prior knowledge of ENHANCE. The lawsuit claims to name those executives.

According to the complaint, a "confidential informant" claims that named members of Schering-Plough's "Brand Team" charged with marketing Vytorin received regular updates about ENHANCE, though the study was supposed to be blinded. The lawsuit also states that the drug maker's principle investigator suspected that Vytorin would show no benefit as early as 2005, and claims that the marketing team knew by 2006 that ENHANCE would not be favorable. Despite this, Schering-Plough continued to promote Vytorin's supposed benefits in its marketing campaign.

The lawsuit claims that withholding the ENHANCE results artificially inflated Schering-Plough's stock price, and that investors depended on the firm's positive statements about Vytorin. Investors suffered when ENHANCE was finally published in 2008, and Schering-Plough's stock fell 55 percent from its high in 2007.

Vytorin Makers Spent Millions on Medical Education

Tue, 15 Sep 2009 00:00:00 -0700

Merck & Co. and Schering-Plough, the makers of Vytorin, spent millions over the past four years to educate doctors about the latest treatments for heart disease, according to The Wall Street Journal. Critics of the pharmaceutical industry assert that marketing, not medical education, is usually behind such generosity.

According to the Journal, Merck and Schering-Plough paid out a total of $60 million to a small group of medical schools and health groups, including Harvard University and the American Heart Association. The funds were used for Continuing Medical Education, or CME. Doctors are required to take CME courses in order to stay current with the latest advances in medical treatments.

Critics of industry funded-CME courses say that the practice could influence doctors prescribing habits, and have charged that the courses sometimes highlight the funding companies' medications over competitors. But Merck, like many other drug makers, insists it has no input into the content of the courses it funds, The Wall Street Journal said.

The Merck and Schering-Plough CME funding was disclosed in a report released by the Senate Special Committee on Aging. "These documents remove any doubt that, at least in this case, when drug companies fund continuing medical education, they see it as money well spent on marketing their latest blockbuster drug," said Sen. Herb Kohl, D-WI, chairman of the Special Committee. Kohl, along with Sen. Chuck Grassley, R.-Iowa, has bee pushing for language in Senate health-care legislation to require companies to disclose such payments, the Journal said.

The CME courses Merck and Schering-Plough funded focused on treatment options for heart disease. According to the Journal, the company's cholesterol drug, Vytorin, has been cited by some in Congress as an example of why there needs to be more transparency regarding the medical industry's financial relationship with doctors, medical schools and medical groups.

Vytorin’s supposed benefits have been the subject of controversy since the ENHANCE study was released in January 2008. ENHANCE found that the drug was no better than a cheaper, generic statin in preventing clogged arteries, and raised serious questions about the effectiveness of Vytorin. What’s more, Merck and Schering-Plough delayed releasing ENHANCE for more than a year, even though the trial was actually completed in 2006.

The ENHANCE controversy spawned scores of lawsuits against Merck and Schering-Plough. Many accused the companies of marketing Vytorin and Zetia in a misleading fashion and failing to disclose the results of ENHANCE in a timely manner. We reported last month that Merck and Schering-Plough agreed to pay $41.5 million to settle class-action lawsuits stemming from that debacle. Several committees in Congress are investigating Vytorin marketing efforts.

No Proof Combo Pills Like Vytorin Work Better, Study Finds

Thu, 03 Sep 2009 00:00:00 -0700

A new study says there is no proof that combo cholesterol lowering drugs like Vytorin work better than high doses of statins.

Vytorin, developed and marketed jointly by Merck and Schering-Plough, is a combination of cholesterol-lowering Zetia and the statin Zocor. Vytorin was approved by the Food & Drug Administration in 2004 to treat both sources of cholesterol - absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues. It was believed that the treatment of cholesterol from both sources would likely to result in lower cholesterol levels. It was likewise theorized that this reduction in cholesterol would in turn reduce the amount of plaque buildup in the arteries, thus reducing the risk of heart attack and stroke.

According to Bloomberg News, in an analysis of 102 studies, researchers found no proof that combo pills like Vytorin extended life expectancy more than taking a high dose of a single statin, like Lipitor. The study was released today by the Annals of Internal Medicine.

The researchers said that few of those studies included in the analysis were long enough to be able to detect a benefit. The study's lead author told Bloomberg News that drugmakers should do larger, long-term studies of combination pills to prove their worth.

Vytorin's supposed benefits have been the subject of controversy since the ENHANCE study was released in January 2008. ENHANCE found that the drug was no better than a cheaper, generic statin in preventing clogged arteries, and raised serious questions about the effectiveness of both Vytorin and Zetia. What’s more, Merck and Schering-Plough delayed releasing ENHANCE for more than a year, even though the trial was actually completed in 2006.

The ENHANCE controversy spawned scores of lawsuits against Merck and Schering-Plough. Many accused the companies of marketing Vytorin and Zetia in a misleading fashion and failing to disclose the results of ENHANCE in a timely manner. Last month, Merck and Schering-Plough agreed to pay $41.5 million to settle class-action lawsuits stemming from that debacle.

Vytorin Makers Announce $41.5 Million Class Action Settlement

Thu, 06 Aug 2009 00:00:00 -0700

The makers of Vytorin are settling more lawsuits. According to a Reuters report, Merck and Schering-Plough will pay $41.5 million to settle class-action lawsuits involving Vytorin and its sister-drug, Zetia.

Vytorin is a combination of Zetia and the statin Zocor. It has been under the microscope since the ENHANCE study was released in January 2008. ENHANCE found that the drug was no better than a cheaper, generic statin in preventing clogged arteries, and raised serious questions about the effectiveness of both Vytorin and Zetia. What's more, Merck and Schering-Plough delayed releasing ENHANCE for more than a year, even though the trial was actually completed in 2006.

The ENHANCE debacle spawned scores of lawsuits against Merck and Schering-Plough. Many accused the companies of marketing Vytorin and Zetia in a misleading fashion and failing to disclose the results of ENHANCE in a timely manner. According to Reuters, the $41.5 million settlement will resolve all the class-action lawsuits that seek economic damages related to the purchase of the two drugs. About 145 such suits are pending, Reuters said.

This is the second Vytorin settlement announced by the companies this summer. In July, we reported that Merck and Schering-Plough had agreed to pay $5.4 million to 35 states and the District of Columbia to settle allegations they delayed the release of negative information from ENHANCE. The attorneys general from the states involved in the settlement had alleged that before the drug makers released any of the negative study results, both Merck and Schering-Plough conducted intense marketing of Vytorin through direct-to-consumer advertising.

Neither settlement announced this summer requires the companies to admit any wrongdoing or liability.

Despite the settlements, Merck and Schering-Plough's Vytorin troubles are far from over. According to The Wall Street Journal, the companies still face a U.S. Department of Justice investigation, as well as lawsuits alleging securities-law violations. The Justice Department is investigating whether the companies' promotion of Vytorin caused false claims to be submitted to federal health-care programs, the Journal said.

Vytorin Named in Another Lawsuit

Tue, 09 Jun 2009 00:00:00 -0700

Vytorin, the controversial cholesterol-lowering drug, has been named in yet another lawsuit. According to Bloomberg.com, the Pennsylvania Employees Benefit Trust Fund (PEBTF) has filed suit against Merck & Co. and Schering-Plough, alleging that the companies charged too much for both Vytorin, and Zetia, another cholesterol drug, which is also a component of Vytorin.

Vytorin, a combination of the statin Zocor (simvastatin) and Zetia, has been under the microscope since the ENHANCE study, which found the drug was no better than a cheaper, generic statin in preventing clogged arteries, was released in January 2008. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – the trial was actually completed in 2006.

The ENHANCE controversy spawned well over 100 lawsuits that allege Merck and Schering-Plough were fraudulent by withholding the study results for so long. Investigations into the ENHANCE debacle and the marketing of Vytorin are also being conducted in Congress, by the U.S. Justice Department and several state attorneys general.

According to Bloomberg, the PEBTF - an insurance fund for active and retired state employees - alleges that Merck and Schering-Plough's misleading claims about Vytorin and Zetia caused consumers to pay too much for the drugs. The lawsuit claims that the companies "suppressed" the results of ENHANCE and used false and deceptive marketing techniques claiming Vytorin was more effective than and just as safe as the much cheaper generic cholesterol drugs.

"For more than a year, Defendants have known (but have failed to make public) that their own study shows that Zetia does not reduce the fatty arterial plaques that can cause heart attack and stroke," the complaint reads. "Despite this knowledge, Defendants have touted the Zetia 'difference,' claiming that it would reduce arterial plaque. Defendants' failure to reveal that Zetia does not in fact reduce arterial plaque constitutes a deceptive practice employed by Defendants to cause physicians to prescribe, and patients to take, Vytorin or Zetia instead of the much less expensive and equally effective generic drug simvastatin."

The PEBTF lawsuit was filed June 5 in Philadelphia federal court, Bloomberg said. The PEBTF is seeking to recoup more than $9 million spent on the two drugs since October 2002.

Vytorin Forum Postings Can Stay In Lawsuit, Judge Says

Wed, 03 Jun 2009 00:00:00 -0700

A judge in a Vytorin lawsuit has decided that some incriminating comments on an internet website frequented by pharmaceutical sales reps can be included in a lawsuit filed by Schering-Plough investors against the company. According to Dow Jones Newswires, the lawsuit alleges that Schering-Plough executives withheld information that Vytorin had failed in an important clinical trial.

Vytorin is a combination of the statin Zocor and the cholesterol-lowering drug Zetia. The drug was marketed jointly by Schering-Plough and Merck & Co. Vytorin has been under the microscope since the ENHANCE study, which found the drug was no better than a cheaper, generic statin in preventing clogged arteries, was released in January 2008. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – the trial was actually completed in 2006.

The ENHANCE controversy spawned well over 100 lawsuits that allege Merck and Schering-Plough were fraudulent by withholding the study results for so long. Investigations are also being conducted in Congress, by the U.S. Justice Department and several state attorneys general.

According to Dow Jones Newswires, the investor lawsuit against Schering-Plough, which was filed in the U.S. District Court in New Jersey, charges the company with violating securities laws by making false and misleading statements and omissions regarding ENHANCE that artificially inflated Schering's share price between 2006 and 2008. Among the evidence plaintiffs' had wanted to introduce in the lawsuit were anonymous posting on the Schering-Plough section of the online forum CafePharma.com that were made before ENHANCE was released, but after the study was completed.

The posting are incriminating. According to Dow Jones Newswire, the author of a March 2007 comment claimed to have a "buddy" at Schering-Plough. "He says that the study is a bust," the post stated. Another post in 2007 stated, "Heard it crashed and burned!" A third, detailed post about the study stated, "Adding Zetia to high dose generic statin provides no real benefit," Dow Jones is reporting.

Schering-Plough had been trying to keep the posts out of the lawsuit. According to Dow Jones, the company characterized CafePharma postings as the equivalent of "scrawls left on a men's room wall." Because they were anonymous, Schering-Plough also asserted that they could have been written by employees from a rival company, people seeking to manipulate the firm's stock price or other "mischief makers."

But the judge in the case has decided that the postings can be presented as evidence. According to Dow Jones, the judge wrote that the postings. "are relevant to the ultimate issue" because they "purport to show the timing within which defendants became aware of the Enhance study's results."

Vytorin Probe Seeks More Information

Fri, 20 Feb 2009 00:00:00 -0800

Lawmakers investigating the cholesterol drug Vytorin have asked Merck and Schering-Plough for more information on the medication's clinical trials. According to Reuters, Rep. Henry Waxman (D-Calif), chairman of the House Energy and Commerce Committee, has written two companies on Thursday seeking additional information about some Vytorin clinical trials.

Vytorin is a combination of the statin Zocor and the cholesterol-lowering drug Zetia. Vytorin has been under the microscope since the ENHANCE study, which found the drug was ineffective in preventing clogged arteries, was released in January 2008. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics have likened to fraud. The delay prompted the House Energy and Commerce Committee to launch an investigation into the way Merck and Schering-Plough handled the ENHANCE findings.

Last March, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology (ACC). A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Then in July, Merck and Shearing-Plough released yet another Vytorin study, SEAS, which was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant, meaning the odds were less than 5 percent that they were the result of chance.

Merck and Schering-Plough called the cancer findings an anomaly. The companies based that claim on an analysis of the SEAS cancer findings that was conducted by Richard Peto, an Oxford University statistician. But when SEAS was published in The New England Journal of Medicine, an accompanying editorial severely criticized Peto's conclusions. The authors of the editorial wrote that a link to cancer deaths “should not be assumed to be a chance finding until further data are in", adding that doctors and patients “are unfortunately left for now with uncertainty about the safety and efficacy of the drug.”

According to today's Reuters report, Waxman is seeking documents regarding the monitoring boards that oversee patient safety in two other Vytorin clinical trials - known as Sharp and Improve It - as part of his committee's ongoing investigation. In September, the companies' lawyers said data for the two other trials should be released before the they conclude, and the boards for the two studies agreed to do so, Waxman's letter said.

Statements from Merck and Schering-Plough said they would cooperate with Waxman's request.

Vytorin Named in 100+ Lawsuits, Justice Department Investigation

Tue, 02 Dec 2008 00:00:00 -0800

Nearly a year after an important Vytorin study raised serious doubts about its effectiveness, Merck and Schering-Plough are facing an increasing number of lawsuits over the controversial cholesterol -lowering drug, the Associated Press Reports. In a filing with the Securities and Exchange Commission (SEC), Merck also said that the marketing of Vytorin was the subject of a Justice Department investigation.

Vytorin is a combination of the statin Zocor and the cholesterol-lowering drug Zetia. Vytorin has been under the microscope since the ENHANCE study, which found the drug was ineffective in preventing clogged arteries, was released last January. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics have likened to fraud. The delay prompted a Congressional investigation into the way Merck and Schering-Plough handled the ENHANCE findings.

According to Merck's SEC filing, the controversy over ENHANCE has resulted in more than 140 class action lawsuits that name Merck and its partner, Schering-Plough, as defendants. According to the Associated Press, some of the lawsuits allege consumer fraud, while others involve claims for personal injury or seek medical monitoring for people who used Vytorin.

The SEC filing also confirms that the companies' promotion of Vytorin is the subject of a Justice Department investigation. According to the Associated Press, that probe is focusing on whether the companies' promotions made false claims to federal health care programs.

News of the lawsuits and investigation is only the latest bad news involving Vytorin, which once promised to be a blockbuster for Merck and Schering-Plough. Vytorin took another hit over the summer, when the SEAS study was released. SEAS was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. Congress recently expanded its Vytorin investigation to include the handling of SEAS.

Experts Divided on Vytorin Cancer Risk

Thu, 13 Nov 2008 00:00:00 -0800

Vytorin was the subject of a heated debate at the annual meeting of the American Heart Association in New Orleans yesterday. At issue was the controversial drug's potential cancer risk. While some heart experts on a panel discussing the issue tried to ease concerns about Vytorin and cancer, others said the drug's various issues of safety and effectiveness warrant more investigation.

Vytorin is a combination of the statin Zocor and the cholesterol-lowering drug Zetia. Vytorin has been under the microscope since the ENHANCE study was released in January. That study showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. When ENHANCE was vetted during the annual meeting of the American College of Cardiology in March, doctors there recommended that it be used only as a last resort. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Vytorin took another hit over the summer, when the SEAS study was released. SEAS was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial, 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance.

Merck and Schering-Plough, the makers of Vytorin, have tried to downplay concerns about the drug's possible cancer risks, calling it an anomaly. The companies based that claim on an analysis conducted by Richard Peto, an Oxford University statistician. Peto pooled data from two much larger ongoing studies of Vytorin and said they showed that the cancer risk was a statistical fluke. He called the contention that Vytorin could cause cancer “bizarre”.

Reuters.com is now reporting that at yesterday's meeting, experts were not able to reach a consensus regarding Vytorin and cancer. Some cautioned against judging Vytorin too soon, and said worries about cancer were unwarranted. "There is no news here other than undue alarm being raised by some about treatments that may well produce further benefits in terms of reducing the risks of heart attacks and strokes," said Rory Collins, an Oxford University researcher.

According to Reuters, Collins is currently leading another Vytorin study called IMPROVE-IT. That study is funded by Merck and Schering-Plough.

Others, however, were more concerned. "I think it is impossible to be completely certain, based upon what we currently know, that there isn't a cancer signal" with Vytorin. Allen Taylor, a cardiologist with Washington Hospital Center in Washington, D.C. According to Reuters, Taylor said that until ongoing large trials definitely prove the safety and effectiveness of the Zetia component of Vytorin, he would only prescribe the drug to patients who had no other alternative.

Feds, State AGs Investigating Vytorin Marketing

Tue, 04 Nov 2008 00:00:00 -0800

Vytorin, Merck and Schering-Plough's controversial cholesterol medication, is the subject of two more state and federal investigations. In a regulatory filing, Merck revealed that the U.S. Justice Department and 35 state attorneys general have opened separate probes into the marketing of Vytorin.

Vytorin has been under the microscope since the ENHANCE study was released in January. That study showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. When ENHANCE was vetted during the annual meeting of the American College of Cardiology in March, doctors there recommended that it be used only as a last resort. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

While the ENHANCE results caused a stir, even more controversy surrounded the way it was handled. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics have likened to fraud. They also at one time attempted to change the study's endpoint - the main result it was meant to measure - after it was completed. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study. The companies dropped their attempt to change the ENHANCE endpoint shortly thereafter.

Vytorin took another hit over the summer, when the SEAS study was released. SEAS was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial, 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance. Congress recently expanded its Vytorin investigation to include the handling of SEAS.

Now, the U.S. Justice Department is asking questions about the way Vytorin was marketed. According to Merck's filing with the Securities and Exchange Commission, the company was notified on September 19 via a letter that the Justice Department's civil division is investigating whether the promotion of Vytorin by Merck and Schering-Plough Corp. caused false claims to be submitted to federal health-care programs.

Merck’s filing also said the company has received five “civil investigative demands” from a multistate group of 35 state attorneys general who are jointly investigating whether Merck and Schering-Plough violated state consumer protection laws when marketing Vytorin.

Merck said in its regulatory filing it's cooperating with these investigations and working with Schering-Plough to respond to the inquiries. The companies have previously disclosed other inquiries by government entities, including Congressional committees and a limited number of state investigators.

In addition, at least 140 lawsuits have been filed alleging consumer fraud in connection with the sale and promotion of the drugs, Merck said.

New Haven to Sue Merck and Schering-Plough

Thu, 16 Oct 2008 00:00:00 -0700

The city of New Haven, Connecticut, is reporting that over $400,000 in tax dollars were spent on Vytorin and Zetia for employees. Now, corporation counsel John Ward is seeking return of that money over ongoing claims that Vitorin “doesn’t work” he said in an interview with The New Haven Independent. Vytorin is a combination cholestral pill comprised of Zetia and Zocor.

Ward has issued an RFP—Request for Proposal—to hire an outside law firm to sue Merck and Schering-Plough. Both Merck and Schering-Plough are currently under Congressional investigation into their handling of Vytorin clinical trial data that called into question Vytorin’s effectiveness. For the suit, Ward is looking to use the “no win, no pay” approach, meaning that the law firm chosen to represent New Haven in the lawsuit would not receive any fee if the city loses the case. Although Ward sought to join a class-action lawsuit, he was unable to find an existing case that matched his needs. In the meantime, New Haven is seeking a firm with experience suing drug makers. “There are no guarantees,” that there’s a firm who wants to take the case, or that the city would win, Ward told the paper, “but I’m just giving it a shot.”

Company spokeswoman, Rosemarie Yancosek, said, “Schering-Plough stands behind our products, and we will defend ourselves vigorously,” noting that Vytorin and Zetia “have consistently demonstrated significant reduction in LDL cholesterol in numerous clinical studies,” and that lowering LDL levels is a “key factor” in lowering cardiovascular risk.

The Vytorin controversy has spurred a rash of over 50 class-action lawsuits. When Ward heard about the controversy, he decided to take action, too, and on September 26, issued an RFP seeking “Legal Services to Recover Excessive Payments of Pharmaceuticals.”

We have long been reporting on the issues with Vytorin, which was developed and marketed jointly by Merck and Schering-Plough and is a combination of cholesterol-lowering Zetia and the statin Zocor. Vytorin was approved by the Food & Drug Administration (FDA) in 2004 to treat both sources of cholesterol: Absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues. It was believed that the treatment of cholesterol from both sources would likely result in lower cholesterol levels. It was likewise theorized that this reduction in cholesterol would, in turn, reduce the amount of plaque buildup in the arteries, thus reducing the risk of heart attack and stroke. Not so, according to this year’s released ENHANCE study that revealed that Vytorin brought about no measurable reduction in the amount of artery plaque buildup. The ENHANCE study was released this January and found that Vytorin worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone.

Even more controversy surrounded the way the ENHANCE study was handled with Merck and Schering-Plough delaying its release for over a year, something critics have likened to fraud. Also, the companies attempted to change the study’s endpoint—the main result it was meant to measure—after it was completed.

Vytorin Sales Dip Means Layoffs at Schering-Plough

Tue, 23 Sep 2008 00:00:00 -0700

The Vytorin controversy is still hurting sales of the once-blockbuster cholesterol drug, with prescriptions down one-third this year. To stem the bleeding, Schering-Plough, which markets Vytorin with Merck & Co., has announced that it will be eliminating 20 percent of its sales force. The elimination of 1000 sales reps is part of companywide reductions announced earlier this year aimed at cutting $1.5 billion in costs by 2012.

Vytorin's troubles started in January, with the release of the long-delayed ENHANCE study. That study showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. When ENHANCE was vetted during the annual meeting of the American College of Cardiology in March, doctors there recommended that it be used only as a last resort. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

While the ENHANCE results caused a stir, even more controversy surrounded the way it was handled. Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics have likened to fraud. In addition, the companies attempted to change the study’s endpoint - the main result it was meant to measure - after it was completed. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study. The companies dropped their attempt to change the ENHANCE endpoint shortly thereafter.

Vytorin took another hit over the summer, when the SEAS study was released. SEAS was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial, 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance.

At the time it released SEAS, Merck and Schering-Plough also released an analysis of ongoing Vytorin trials that they said showed the SEAS cancer results to be an anomaly. But not everyone is convinced, and Congress recently expanded its Vytorin investigation to include the handling of SEAS.

At its peak, Vytorin posted sales of $5 billion. With its sales now in the tank, Schering-Plough had to find ways to reduce costs. Schering-Plough Chief Executive Officer Fred Hassan said in April that the company would trim 10 percent off its 2007 costs to offset the decline. In addition to reducing the sales force, Schering-Plough is firing workers after acquiring Organon Biosciences NV.

“The company emphasized that it highly values the work of its sales professionals, and so the decision to eliminate positions was difficult,” Schering-Plough said in a statement announcing the cuts.

Vytorin Researcher Denies Cancer Link

Fri, 19 Sep 2008 00:00:00 -0700

A prominent statistician is continuing to insist that there is no link between Vytorin and cancer. In a blunt letter to a Congressional Committee investigating Vytorin, Sir Richard Peto, of Oxford University, said that “any competent trial statistician would endorse” his conclusion that there’s “no credible evidence” that the cholesterol drug is tied to increased cancer risk. While Peto's letter is rather scathing in its dismissal of the Committee's concerns, it does not answer other criticism of his conclusions recently raised by a prominent medical journal.

Peto conducted an analysis of cancer data in three Vytorin trials that was released at the same time as the now notorious SEAS trial. SEAS was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.

Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant", meaning the odds were less than 5 percent that they were the result of chance. But based on his analysis, Peto called the idea that Vytorin was linked to cancer or cancer deaths bizarre.

The House Energy and Commerce Committee, which had already been probing the controversial Vytorin study known as ENHANCE, expanded its investigation to the SEAS controversy. The Committee has since written two letters to Merck and Schering-Plough, asking for more information on SEAS and Peto's analysis.

In his letter to the Committee, Peto writes that he can best answer many of its questions. The letter states that “the main conclusion (of the SEAS trial) was that the trial results provide ‘no credible evidence’ that (Vytorin) affects cancer rates. He goes on to say that the "key scientific points that our reports make would be selfevidently true to any competent statistician.”

Peto also denies assertions that he may have a conflict of interest. He and his colleagues, he writes, take no honoraria, consultancy fees or other payments, although companies occasionally pay for their travel accommodations. Peto also states that salaries of researchers are "not directly or indirectly paid for by industry or industry-sponsored projects."

Finally, Peto calls the Committees request for all correspondence with Merck & Schering-Plough "inappropriate harassment". Peto says that complying with the request required an “unreasonably vast amount of effort,” as his unit at Oxford has worked with the companies on trials involving about 60,000 patients.

What Peto does not address in his letter, however, is the New England Journal of Medicine's recent criticism of his Vytorin analysis. When the journal published the SEAS study and Peto's analysis, it also issued an editorial saying that the Vytorin cancer link shouldn't be attributed to chance "until further data are in."

Vytorin Confusion Leaves Patients Wondering

Mon, 08 Sep 2008 00:00:00 -0700

Many patients - and probably some doctors - are scratching their heads over Vytorin. Though it has been on the market for four years, little is known about its safety and effectiveness. This year, two studies - ENHANCE and SEAS - have only added to the confusion over the cholesterol drug. Both concluded that Vytorin offered little added benefit when compared with cheaper drugs, while the latter indicated that the medication could be linked to cancer. Still, Merck & Schering-Plough are standing by their former blockbuster, hoping that larger clinical trials will vindicate it. Unfortunately for patients, those trials are years from completion.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia (ezetimibe) and the statin Zocor (simvastin). Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. Theoretically, that should translate to fewer heart attacks, clogged arteries and the like, but there is no actual proof of that yet.

Questions over the safety and effectiveness of Vytorin were first raised in January, when the long-awaited ENHANCE study was finally released. ENHANCE showed Vytorin were ineffective in preventing clogged arteries, and might actually increase plaque in some users. Adding to the controversy was the fact that Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

In March, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology (ACC). A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

In July, Merck & Shearing-Plough released yet another Vytorin study, SEAS, which was designed to see if the drug helped people with aortic stenosis avoid heart attacks. Not only did SEAS show that Vytorin offered no additional heart attack prevention, but Vytorin patients enrolled in the study had higher rates of cancer than those taking a placebo. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant, meaning the odds were less than 5 percent that they were the result of chance.

Merck and Schering-Plough called the cancer findings an anomaly. The companies based that claim on an analysis of the SEAS cancer findings that was conducted by Richard Peto, an Oxford University statistician. Peto pooled data from two much larger ongoing studies of Vytorin and said they showed that the cancer risk was a statistical fluke. He called the contention that Vytorin could cause cancer “bizarre”.

But last week, when SEAS was published in the New England Journal of Medicine, the editors of the journal also published a strongly worded editorial criticizing Peto’s findings. The authors of the editorial wrote that a link to cancer deaths “should not be assumed to be a chance finding until further data are in,”, adding that doctors and patients “are unfortunately left for now with uncertainty about the safety and efficacy of the drug.”

Thanks to ENHANCE and SEAS, Vytorin is now mired in confusion and controversy. Unfortunately, a clearer picture of the drug's effectiveness and safety is not likely to emerge until 2012, when larger clinical trials are finally complete. That's not much comfort for patients taking Vytorin now.

Vytorin Study Release Criticized

Wed, 03 Sep 2008 00:00:00 -0700

The behavior of Vytorin makers, Merck and Schering-Plough, in releasing the results of an important clinical trial that indicated the cholesterol drug might be linked to cancer has many cardiologists up in arms. According to a report on Forbes.com, while doctors are divided over exactly how the cancer data should be interpreted, there seems to be a consensus that the companies were wrong to make the results of the SEAS study public via a news conference, rather than first publishing them in a medical journal were they would have been vetted by a team of outside medical experts.

The SEAS study investigated the effects of Vytorin in patients with partial blockages of the aortic valve of the heart, known as aortic stenosis. According to the SEAS findings, Vytorin did little to help patients with aortic stenosis avoid other heart problems. But in a real stunner, SEAS also found that Vytorin patients in the study had higher rates of cancer and cancer deaths. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.

In an attempt at damage control, Merck and Schering-Plough quickly organized a press conference on July 21 to release the data. There, Richard Peto, an Oxford University statistician, presented data from an analysis that pooled data from two much larger ongoing studies of Vytorin and said they showed that the cancer risk was a statistical fluke. He called the contention that Vytorin could cause cancer "bizarre".

Terje Pedersen, the lead investigator of the SEAS study, told Forbrs.com that he “wanted to do this in peace and quiet” and present the full results at the annual meeting of the American Heart Association in New Orleans in November. But he had no choice but to publicize them early, because Merck and Schering-Plough told him they needed to release the results to the Food and Drug Administration. Pedersen also said the companies wanted to release a bare bones version of SEAS to investors.

At least one critic of Vytorin sees Merck and Schering-Plough's rush to release SEAS as damage control. Dr. Stephen Nissan, a cardiologist at the Cleveland Clinic, told Forbes that "they’re trying to spin the results using media relations strategies rather than the proper scientific approach.”

The full SEAS study was finally published in the New England Journal of Medicine (NEJM) this week. An editorial in the same NEJM issue sharply criticized Peto's analysis, with the editors writing that a link to cancer deaths “should not be assumed to be a chance finding until further data are in,”, adding that doctors and patients “are unfortunately left for now with uncertainty about the safety and efficacy of the drug.”

This is not the first time that Merck and Schering-Plough have come under fire for a Vytorin study. The drug has been a subject of controversy since January, when Merck and Schering-Plough finally released the long-delayed ENHANCE study. ENHANCE showed Vytorin were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

Vytorin Cancer Controversy Far from Over

Thu, 28 Aug 2008 00:00:00 -0700

News earlier this summer that Vytorin had been tied to a higher risk of cancer by a newly published study quickly faded from the headlines. Merck and Schering-Plough's reassurance that the cancer finding in the SEAS study was an anomaly apparently squashed much discussion of the issue - at least in the media. But a new report on Fortune.com seems to indicate that a change is coming, and Vytorin could face new scrutiny next week

The SEAS study investigated the effects of Vytorin in patients with partial blockages of the aortic valve of the heart, known as aortic stenosis. Left untreated, it can progress to death from heart failure or cardiac arrest. According to the SEAS findings, Vytorin did little to help patients with aortic stenosis avoid other heart problems.

But even more disturbing, a subsequent safety analysis of SEAS found that Vytorin patients in the study had higher rates of cancer and cancer deaths. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.

Such news should have created a firestorm. But according to Forbes, the way Merck and Schering-Plough released the SEAS data helped mitigate fallout. According to Forbes, "Researchers involved in the study put together a hastily organized, company-funded press conference on July 21 to release the data."

There, Richard Peto, an Oxford University statistician, "pooled data from two much larger ongoing studies of Vytorin and said they showed that the cancer risk was a statistical fluke. He called the contention that Vytorin could cause cancer 'bizarre',” according to Forbes.

But some experts say Peto's analysis doesn't stand up to scrutiny, and that might become apparent when the full SEAS study is released next week. For its article, Forbes surveyed more than dozen top experts about SEAS. While none were yet convinced that Vytorin increased cancer risk, at least 8 said that Peto was wrong to completely dismiss the possibility. Ten thought there was at least some chance that Vytorin increases the risk of death for patients who have cancer. Peto's analysis did not even address that possibility.

Several experts interviewed by Forbes said that there is just not enough information available to reach conclusions about Vytorin's cancer risks. The data "are not definitive at all," says James Stein, a cardiologist at the University of Wisconsin, Madison. He told Forbes that Vytorin should remain "a third-line drug" until more data can be collected.

Next week, when the entire SEAS study is vetted, it is likely that many more experts will voice similar concerns.

Lawmakers Pressing for Answers on Vytorin Study

Thu, 21 Aug 2008 00:00:00 -0700

Two lawmakers want to know why the press release detailing a Vytorin study issued by drug makers Merck and Schering-Plough differed from information released by the study's authors. Rep. John Dingell, D-Mich., Chairman of the House Energy and Commerce Committee, and Rep. Bart Stupak, D-Mich., say they are "troubled" by the confusing nature of the information, and have written the companies, asking them to clarify which data are correct.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia (ezetimibe) and the statin Zocor (simvastin). Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines.

The study that has attracted the attention of Dingell and Stupak is known as SEAS. It involved 1873 patients, and investigated the effects of Vytorin in patients with aortic stenosis. Aortic stenosis involves partial blockage of the aortic valve in the heart. Left untreated, it can progress to death from heart failure or cardiac arrest. Aortic valve replacement for severe symptoms is the second most frequent type of heart surgery. Apart from surgery, there is no medical therapy known to prevent or heal this condition.

In addition to failing to show that Vytorin did much to help patients with aortic stenosis avoid other heart problems, a safety analysis of SEAS found that Vytorin patients in the study had higher rates of cancer and cancer deaths. According to information released by researchers, 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo.

But Merck and Schering-Plough's press release said there were only 93 cancer cases among patients taking Vytorin, with 65 among people on a placebo. In the press release, the companies have maintained that the SEAS cancer findings are an anomaly, and said that an analysis of the findings authored by Sir Richard Peto, co-director of the Oxford University Clinical Trials Service Unit, had reached such a conclusion.

So far, Merck and Schering-Plough have not released that report to the House Energy Committee because the companies don't want it made public. However, the FDA has been given a copy of the report.

Dingell and Stupak said they found the companies' reluctance to furnish the study to the committee "questionable". They also question Peto's ties to both Merck and Schering-Plough, and want to know if he or the Clinical Trials Service Unit were paid by the companies.

The House Energy and Commerce Committee has been investigating Vytorin since January, when Merck and Schering-Plough finally released the long-delayed ENHANCE study. ENHANCE showed Vytorin were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

FDA Taking a Look at Vytorin - Cancer Link

Thu, 21 Aug 2008 00:00:00 -0700

Vytorin is being investigated by federal regulators for a possible link to cancer. The investigation stems from the publication last month of the SEAS study, which found that patients taking Vytorin had a higher rate of cancer than those taking a placebo.

Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance.

In a notice on its website, the Food & Drug Administration (FDA) announced that it was going to investigate the possible association between the use of Vytorin and cancer reported in the SEAS trial.

Despite the safety review, the agency is not telling anyone to stop taking Vytorin. That's because, according to the FDA, interim data from two large ongoing cardiovascular trials of Vytorin – the Study of Heart and Renal Protection (SHARP) and the Improved Reduction in High-Risk Subjects Presenting with Acute Coronary Syndrome (IMPROVE-IT) – so far have not shown an increased risk of cancer with Vytorin. The SHARP trial is expected to be completed in 2010. The IMPROVE-IT trial is scheduled for completion around 2012.

The FDA said safety data from both SHARP and IMPROVE-IT are being evaluated on a regular basis by independent data safety monitoring boards. For now, the FDA says the cancer findings in the SEAS trial plus the interim data from SHARP and IMPROVE-IT should not prompt patients to stop taking Vytorin or any other cholesterol lowering drug.

The FDA will be receiving a final SEAS study report in about 3 months. Once FDA receives the final study report, it will likely take 6 months to fully evaluate the clinical trial data and other relevant information. As soon as this review is complete, the FDA says it will communicate its conclusions and recommendations to the public.

The FDA is already reviewing another Vytorin study, ENHANCE, that was released earlier this year. EHANCE showed Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users.

The ENHANCE study was supposed to have been released by Merck and Schering-Plough in November 2006. However, the release of ENHANCE was delayed twice by the companies. The drug makers also tried changing the ENHANCE study’s endpoint – the main medical result the study was meant to measure. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged.

Merck and Schering-Plough backed off changing the ENHANCE endpoint and finally released the preliminary results of the study on January 14 in the form of a press release. But some have likened the companies' delays and their attempt to change the endpoint of ENHANCE to fraud. As a result, Vytorin faces a Congressional investigation, as well as probes by the Department of Justice and several state Attorneys General.

Simvastatin and Amiodarone Linked to Possibly Fatal Muscle Disease

Fri, 08 Aug 2008 00:00:00 -0700

The combination of simvastatin and amiodarone, an anti-arrhythmia medication, has been linked to a rare muscle condition that can cause kidney damage and death. The Food & Drug Administration (FDA) first warned against combining the drugs in 2002 because of their association with the condition - called rhabdomyolysis - but has continued to received reports of its occurrence.

Amiodarone is an ingredient in Wyeth's Cordarone and is also sold generically. Simvastatin is an ingredient in Merck & Co's Zocor and Abbott Laboratories Inc's Simcor, and is sold generically. It also a component of Merck and Schering-Plough Corp's Vytorin.

Simvastatin is a statin, a class of drugs which already carries a risk of rhabdomyolysis. However, the FDA said today that the risk of developing rhabdomyolysis is more pronounced when simvastatin is combined with amiodarone than it is with other statin medications.

Rhabdomyolysis is a muscle injury that causes the rapid breakdown of skeletal muscle tissue. The destruction of the muscle leads to the release of the breakdown products of damaged muscle cells into the bloodstream; some of these, such as myoglobin, are harmful to the kidney and may lead to acute kidney failure.

According to today's FDA warning, the risk of developing rhabdomyolysis is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. The agency said that healthcare professionals, who prescribe simvastatin or simvastatin-containing medications (Simcor, Zocor, Vytorin), should be aware that patients taking amiodarone should not take more than 20 mg per day of simvastatin.

Patients starting therapy with simvastatin, or who have had their dose of simvastatin increased, should contact their doctor immediately if they experience symptoms of unexplained muscle injury, such as muscle cramps, pain, tenderness, stiffness or spasm.

The FDA said it is working with the manufacturer of Cordarone (amiodarone) to modify prescribing information to warn of an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses exceeding 20 mg daily. In 2002, the labeling of simvastatin was changed to include similar information.

Vytorin - Cancer Link Draws Congressional Scrutiny

Fri, 01 Aug 2008 00:00:00 -0700

Lawmakers on a congressional committee want to see the results of a new study that indicated patients taking Vytorin might be at a higher risk of cancer. That study, known as SEAS, was given to the Food & Drug Administration (FDA), but has yet to be turned over to the House Energy and Commerce Committee, which has been investigating Vytorin for months.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia (ezetimibe) and the statin Zocor (simvastin). Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines.

SEAS was presented last month in London by its primary researcher, Dr. Terje Pedersen of Ulleval University Hospital in Oslo, Norway. The study, which involved 1873 patients, investigated the effects of Vytorin in patients with aortic stenosis. Aortic stenosis involves partial blockage of the aortic valve in the heart. Left untreated, it can progress to death from heart failure or cardiac arrest. Aortic valve replacement for severe symptoms is the second most frequent type of heart surgery. Apart from surgery, there is no medical therapy known to prevent or heal this condition.

In addition to failing to show that Vytorin did much to help patients with aortic stenosis avoid other heart problems, a safety analysis of SEAS found that Vytorin patients in the study had higher rates of cancer and cancer deaths. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo. Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance.

Both Merck and Schering-Plough have called the cancer findings an "anomaly", but members of the House Energy and Commerce Committee aren't so sure. According to The Wall Street Journal, in a letter to the FDA, Rep. John Dingell (D-Mich), Chairman of the committee, said that based on the study's finding, "Vytorin may not be safe. Its potential for cancer and cancer deaths may be a significant cause for concern among physicians and patients."

Dingell has asked the FDA to turn over an assessment of the SEAS study that was written by Dr. Richard Peto, an epidemiologist at Oxford University, and related records within two weeks. Dr. Peto's analysis, which was funded by Merck and Schering-Plough, said SEAS' cancer findings were largely due to chance and "implausible."

The House Energy and Commerce Committee has been investigating Vytorin since January, when Merck and Schering-Plough finally released the long-delayed ENHANCE study. ENHANCE showed Vytorin were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

Vytorin Makers Defend Drug Following Cancer Findings

Thu, 24 Jul 2008 00:00:00 -0700

Vytorin makers Merck and Schering-Plough are preparing to send a letter to thousands of physicians in an attempt to address cancer concerns raised by a recently published study.   While the companies acknowledge that Vytorin users enrolled in the SEAS study had higher rates of cancer than those taking placebo, the letter characterized the finding as an "anomaly".

This latest Vytorin study - known as SEAS - was presented Monday in London by its primary researcher, Dr. Terje Pedersen of Ulleval University Hospital in Oslo, Norway. The study, which involved 1873 patients, investigated the effects of Vytorn in patients with aortic stenosis. Aortic stenosis involves partial blockage of the aortic valve in the heart. Left untreated, it can progress to death from heart failure or cardiac arrest. Aortic valve replacement for severe symptoms is the second most frequent type of heart surgery. Apart from surgery, there is no medical therapy known to prevent or heal this condition

In addition to failing to show that Vytorin did much to help patients with aortic stenosis avoid other heart problems, a safety analysis of SEAS found that Vytorin patients in the study had higher rates of cancer and cancer deaths. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.   Researchers conducting the study said that while those numbers don’t prove a definitive cancer link, they were “statistically significant”, meaning the odds were less than 5 percent that they were the result of chance.

In a letter being sent to doctors, Merck and Schering-Plough state that "the cancer finding in SEAS is likely to be an anomaly that, taken in the light of all the available data, does not support an association with Vytorin".   The companies said they have made the Food & Drug Administration (FDA) aware of the SEAS findings, " we do not believe that changes in the clinical use of Vytorin are warranted."

Vytorin has been under fire since January, when Merck and Schering-Plough finally released the long-delayed ENHANCE study. ENHANCE showed Vytorin were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

In March, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology (ACC). A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Another Vytorin Failure

Tue, 22 Jul 2008 00:00:00 -0700

Yesterday's news that Vytorin failed to meet the primary endpoint in another important study has not done much to restore faith in the controversial cholesterol drug.   First shown to be ineffective in preventing clogged arteries, it now seems Vytorin does little to help patients with aortic stenosis avoid other heart problems. Concerns have also been raised that Vytorin could also be linked to an increased risk of cancer. Doctors have already cut way back on the number of Vytorin prescriptions they have been writing, and it seems unlikely that yesterday's developments will discourage that trend.

The study results released yesterday - from the so-called SEAS trial - involved nearly 1,900 patients whose heart valves were partially blocked, participants were given either Vytorin or a placebo pill that contained no medicine. Scientists hoped that the trial would show that patients taking Vytorin would have a lower risk of needing valve replacement surgery or having heart failure. But the drug did not show those benefits.

However, patients taking Vytorin in the trial did have a much higher risk of developing and dying from cancer. In the trial 102 patients taking Vytorin developed cancer, compared with 67 taking the placebo. Of those, 39 people taking Vytorin died from their cancer, compared with 23 taking placebo.   Researchers conducting the study said that while those numbers don't prove a definitive cancer link, they were "statistically significant", meaning the odds were less than 5 percent that they were the result of chance.

Dr. Steven Nissen, a former president of the American College of Cardiology and a longtime critic of Vytorin, told The New York Times that the results of the SEAS trial will increase concerns over the safety and effectiveness of Vytorin.   Earlier this year, after a study called ENHANCE failed to show Vytorin reduced clogged arteries, leading a panel of top cardiologists to recommend using Vytorin only as a last resort.

Vytorin Falls Short in Another Study, Possible Cancer Link Found

Mon, 21 Jul 2008 00:00:00 -0700

Vytorin, the controversial cholesterol drug sold by Merck and Schering-Plough, failed to meet the main goal in another important study. What's worse, the study also found that patients taking Vytorin in the study were more likely to develop cancer.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia (ezetimibe) and the statin Zocor (simvastin). Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines.

This latest Vytorin study - known as SEAS - was presented Monday in London by its primary researcher, Dr. Terje Pedersen of Ulleval University Hospital in Oslo, Norway. The study investigated the effects of Vytorn in patients with aortic stenosis. Aortic stenosis involves partial blockage of the aortic valve in the heart. Left untreated, it can progress to death from heart failure or cardiac arrest. Aortic valve replacement for severe symptoms is the second most frequent type of heart surgery. Apart from surgery, there is no medical therapy known to prevent or heal this condition

High levels of LDL (bad) cholesterol have been known to be associated with the development of aortic stenosis. The SEAS study is the first large-scale randomized trial to assess the effects of lowering LDL-cholesterol in patients with aortic stenosis. It included 1873 patients with mild to moderate aortic stenosis without symptoms who were not considered to have a clear indication for treatment with cholesterol-lowering drugs. Patients were randomly assigned to receive either intensive cholesterol lowering with Vytorin or matching placebo.

The researchers found that Vytorin was no better than placebo at lowering the risk of major cardiovascular events in patients suffering from aortic stenosis. Vytorin also failed to meet a secondary goal of improving aortic valve disease events, which included valve replacement surgery, hospitalization because of heart failure, and death related to heart.

Vytorin did meet the study's secondary goal of reducing atherosclerotic disease, in which plaque builds up and blocks an artery. Events included in the study assessment were nonfatal heart attacks, the need for bypass surgery, and strokes.

According to the researchers a total of 158 patients enrolled in the study "were recorded with a serious adverse event attributed to cancer." Of these events, 93 occurred among patents taking Vytorn and 65 in patients assigned a placebo. There were 39 cancer deaths among the Vytorin group, and only 23 among those taking a placebo.

Because the SEAS study was small, researchers said that they could not determine what role Vytorin played in the cancer incidents. In order to assess their relevance, the SEAS data have been provided to an independent academic group for combined analysis with data on cancer from the two other large trials of Vytorin, which are still in progress.

SEAS is the second study to cast doubt on the effectiveness of Vytorin. The ENHANCE study, which was released on January 14, showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. When ENHANCE was vetted during the annual meeting of the American College of Cardiology in March, doctors there recommended that it be used only as a last resort. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Drug Makers Decry FDA Safety Push

Tue, 01 Jul 2008 00:00:00 -0700

Drug makers are complaining that the Food & Drug Administration (FDA) is too focused on, of all things, safety. The pharmaceutical industry says the FDA' s tougher stance is slowing the arrival of new drugs to the market, but consumer advocates - citing recent scandals involving defective drugs - say a stronger focus on safety is long overdue.

According to the Wall Street Journal, the FDA approved just 19 new medicines last year, the fewest in 24 years, and announced about 75 new or revised "black-box" warnings about potential side effects -- the agency's strongest -- twice the number in 2004. The number of so-called approvable letters, which typically postpone FDA approval decisions pending more data, increased by 40% last year.

Drug makers are less-than-enthusiastic about the FDA's new approach. Schering-Plough Corp. Chief Executive Fred Hassan told The Wall Street Journal that the new safety focus means that drug companies must now spend significantly more time and money to get a drug approved - and even then, approval is not guaranteed. "What will it take to get new drugs approved?" Hassan said. "The point is, we don't know."

The FDA's new caution can be traced to the Vioxx debacle. Vioxx was approved for use in 1999, and quickly became a blockbuster for Merck, with annual sales of $2.5 billion. The FDA ordered the painkiller off the market after an analysis of patients using Vioxx linked the defective drug to more than 27,000 heart attacks or sudden cardiac deaths in the U.S. from 1999 through 2003.

Shortly after Vioxx was pulled from the market, it was revealed the FDA had tried to silence the drug expert who headed that analysis. Dr. David Graham, associate director for science in the FDA Drug Center’s Office of Drug Safety, told Senate investigators that he had been subjected to veiled threats and intimidation when he informed the FDA of his findings.

Following the Vioxx mess, several other drug safety scandals intensified pressure on the agency. For instance, after a study was published last May detailing heart risks with the diabetes drug Avandia, it was revealed that in 2005 GlaxoSmithKline had informed the FDA of a study it had conducted that produced similar results. However, both the agency and the manufacturer felt that more investigation was needed before conclusions could be made about Avandia’s possible safety issues.

And just this year, it was learned that the makers of Vytorin withheld a study that found the expensive cholesterol medication was no more effective than cheaper statins for two years. Poor FDA oversight of foreign drug plants allowed tainted heparin to kill at least 149 people this year, and the agency has been slow to take strong action against the stop-smoking drug Chantix, which has been linked to suicides.

These and other scandals have strained the credibility of both the FDA and the pharmaceutical industry. The FDA has apparently heard the criticism. In addition to being tougher on new drug approvals, the agency is adding warnings about cancer risk to arthritis drugs for children, and warnings about suicide risk to epilepsy drugs. The FDA is also considering instituting tougher approval criteria for diabetes drugs.

None of this sets well with the pharmaceutical industry, which relies on new drug approvals to stay in the black. But considering the industry's recent history of manipulating clinical data, concealing dangerous side effects and aggressively promoting risky products, drug makers have only themselves to blame.

Senator McCain Quit Vytorin After ENHANCE

Wed, 28 May 2008 00:00:00 -0700

Many former Vytorin patients switched off the expensive drug after a study -called ENHANCE - released earlier this year showed it was no more effective than cheaper statins. Now it turns out that one of those patients was none other than Republican presidential nominee Senator John McCain.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor - known generically as simvastatin. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. In March, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology (ACC). A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Last week, the McCain campaign released the Senators health records. Apparently, the presidential candidate was taking Vytorin until the ACC made its recommendation. At that time, Sen. McCain's internist had him start taking a generic statin instead. Since the switch, the Senator's LDL (bad) cholesterol has jumped from 83 to 123. Some doctors who spoke with The Wall Street Journal were of the opinion that Sen. McCain should be taking a higher dose of the generic statin, or should switch to a more potent type of statin.

Some Vytorin critics also told the Journal that it was patients like McCain that caused them to be concerned about the once-popular drug. Chris Cannon, a cardiologist at Brigham and Women’s Hospital, Boston said that there isn’t any evidence that combining 10 milligrams of Zetia and 10 milligrams of simvastatin reduces heart attack risk despite the lower LDL levels. But patients like McCain, by achieving an LDL of 83, might be lulled into thinking they were getting the benefit.

Vytorin Study Probed by US Justice Department

Fri, 09 May 2008 00:00:00 -0700

The US Justice Department wants to know more about a crucial Vytorin study, the results of which were concealed for more than a year. Known as ENHANCE, the study found that Vytorin was no more effective at preventing clogged arteries than less expensive statin drugs. The Justice Department probe is just one of many looking into the way ENHANCE was handled.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. In addition, the companies attempted to change the study's endpoint - the main result it was meant to measure - after it was completed. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study. The companies dropped their attempt to change the ENHANCE endpoint shortly thereafter.

In its regular quarterly filing with the Securities and Exchange Commission, Schering-Plough said it received "requests for information'' from an unspecified number of U.S. attorneys' offices. The information requests involved the company's handling of ENHANCE. Vytorin was already the subject of a Congressional investigation, as well as probes by several state attorneys' general.

Last month, the House of Representatives Energy and Commerce Committee released some Schering-Plough documents that raised disturbing questions about the way ENHANCE as handled. Those documents related to a meeting held in November 2007 where ENHANCE was discussed. According to The Wall Street Journal, the minutes of that meeting suggested that outside consultants had recommended that the companies change the ENHANCE endpoint.

But other documents released by the Congressional Committee disputed the minutes. After receiving the minutes, James Stein, a cardiac-imaging expert at the University of Wisconsin who was present at the November meeting, wrote in an email to a Schering-Plough scientist: “It was my understanding that there were no minutes or transcript of this meeting.” He also told a company scientist in an email: “We did not vote on this….It was the decision of the company to change the endpoint.”

Lawmakers Lean on FDA to Police Drug Advertising

Thu, 08 May 2008 00:00:00 -0700

Last month, Congress asked the Food and Drug Administration (FDA) to speed its efforts in forcing drug companies to include safety-reporting information in television and radio ads. Now, Congressional Democrats are placing more pressure on the drug industry's direct-to-consumer advertising following increased problems over the marketing of several popular drugs, including Vytorin, Lipitor, and Procrit.

Last year, Democrats lost a fight to increase government regulation of TV commercials for prescription drugs; however, recent controversies have helped Democrats on the House Energy and Commerce Committee. Also, late last month, drug maker AstraZeneca Plc urged U.S. lawmakers to revive a program for drug makers who want to voluntarily submit their television commercials for regulatory review. Congress created the program last year but it has not taken effect and lawmakers failed to give the FDA full authority to collect and spend industry fees to fund reviews. Because the system is voluntary, FDA scientists are concerned it misses most adverse drug reactions.

Direct-to-consumer drug marketing nets billions in sales for drug makers and the television industry. In 1997, the government relaxed TV and radio ads rules, allowing drug makers to shorten warnings on side effects in commercials; since then, pharmaceutical makers have spent about $14 billion on broadcast and cable TV ads for prescription drugs, making that a major television revenue stream.

A subcommittee led by Michigan Democrat Bart Stupak scheduled a hearing today entitled "Direct to Consumer Advertising: Marketing, Education, or Deception?" Stupak says his purpose is to “lay the groundwork” for future legislation to tighten controls on drug marketing, which includes giving the FDA the ability to force changes in TV drug ads before broadcast. "The drug and TV and cable industries have formed a cabal here to protect their revenues," said Gene Kimmelman of Consumers Union, an advocacy group looking for stricter limits on direct-to-consumer drug marketing

Merck & Co. and Schering-Plough have been harshly criticized for their promotion of cholesterol drug Vytorin and not disclosing a study questioning Vytorin’s effectiveness. Pfizer Inc. featured Robert Jarvik, the inventor of the artificial heart in commercials in which “he appears to be giving medical advice,” according to the committee, which suggests the ads are misleading. Jarvik in neither a cardiologist nor a practicing physician.

Stupak says Procrit marketers Johnson & Johnson, and its subsidiary Ortho Biotech, broadcast ads promoting Procrit as an anti-fatigue medication. Procrit was not approved for this purpose and the FDA repeatedly called for the company to revise its ads. "They advertised this for seven years," said Stupak, calling the actions a violation of off-label-use prohibitions. Stupak said political appointees leading the FDA's legal advisory team effectively shut down the FDA's marketing regulators during the current administration and the FDA's letters to J&J and Ortho Biotech complaining about the TV marketing stopped in 2001, just before the FDA instituted a policy of first sending warnings to companies through the FDA chief counsel's office for review. The company stopped running the TV ads in 2005 and print ads in 2006. Procrit was later linked to increased risk of tumor growth in certain patient and a panel of experts advising the FDA questioned if Procrit was being overused in cancer patients.

Vytorin, Procrit, Lipitor TV Ads Subject of Congress Probe

Tue, 06 May 2008 00:00:00 -0700

A U.S. congressional panel is now examining television ads for cholesterol drugs Lipitor and Vytorin and for the anemia drug Procrit at a Thursday hearing. The panel is looking to determine if such commercials are deceptive or misleading. Representatives of the companies that make the drugs—Pfizer Inc., Johnson & Johnson, Merck & Co Inc, and Schering-Plough Corporation—will testify at the hearing, according to a notice issued on Monday by the U.S. House of Representatives Energy and Commerce Committee.

The House committee, which began investigating drug advertising in January, will spotlight a series of Vytorin commercials that cite "food and family" as two sources of cholesterol. Merck and Schering-Plough, which sell Vytorin through a joint venture, pulled those ads in January after reporting the drug failed to keep arteries any clearer than an older generic drug, Zocor. Merck and Schering-Plough concealed that data for nearly two years and while withholding those results, the companies continued spending at least $155 million annually on clever TV ads that heralded Vytorin’s supposed superiority over statins alone.

The companies have continued their print versions of the ad, said Skip Irvine, spokesman for the Merck and Schering-Plough joint venture, who confirmed the companies were asked to appear before the committee but could not say who would represent them. Irvine said they would make a statement at the hearing but offered no other details.

Lawmakers will also look at Pfizer's Lipitor television commercials featuring the inventor of the Jarvik artificial heart, Dr. Robert Jarvik. The Jarvik ad campaign came under Congressional committee scrutiny when examining consumer drug advertising and questions if the ads misrepresented Jarvik and his credentials. While Jarvik does have a medical degree, he is neither a cardiologist, nor is he licensed to practice medicine. In one ad, Jarvik is presented as an accomplished rower; that ad used a body double for Jarvik, who does not row. “The way in which we presented Dr. Jarvik in these ads has, unfortunately, led to misimpressions and distractions from our primary goal of encouraging patient and physician dialogue on the leading cause of death in the world—cardiovascular disease,” Pfizer’s president of worldwide pharmaceutical operations, Ian Read, said. “We regret this. Going forward, we commit to ensuring there is greater clarity in our advertising regarding the presentation of spokespeople.” A company spokeswoman, Vanessa Aristide, said Pfizer was working with its ad agency, the Kaplan Thaler Group, on a new campaign. Pfizer pulled the long-running Lipitor ads in February, but spent over $258 million in advertising since January 2006, mostly on the Jarvik campaign, hoping to protect Lipitor from competition by cheaper generics.

It was not immediately clear which of Johnson & Johnson's Procrit ads would be examined at the committee hearing. In a statement, Johnson & Johnson's Ortho Biotech unit, which makes Procrit, said the company was cooperating with the committee.

The House panel, which is led by Democrat John Dingell of Michigan, will also examine the effects of consumer drug advertising on prescribing habits and sales, among other issues.

FDA Planning Hiring Blitz

Thu, 01 May 2008 00:00:00 -0700

The beleaguered Food & Drug Administration (FDA) is planning on filling over 1,300 positions by the end of September, triple the amount hired by the FDA over the past two years. The FDA will add 600 new jobs—including chemists, biologists, and statisticians—and will fill over 700 currently open posts. Most of the new positions will be in the department charged with reviewing new drugs; 150 will be in field offices that inspect manufacturing plants and food centers. The FDA currently has 10,000 employees.

Approximately 500 of the new positions will be funded by user fees paid to the FDA by drug makers filing applications to market new products, according to Christopher Kelly, FDA spokesman. These fees were appropriated from Congress as part of legislation passed in September that renewed and increased fees paid to the FDA by makers of drugs and medical devices, Kelly said. The FDA will hold recruitment fairs and conferences to fill the positions and most of the jobs will be at the FDA’s new headquarters in White Oak, Maryland.

The FDA has recently been under intense Congressional scrutiny due to the tragedies linked to the contaminated blood thinner heparin, tainted pet food, and the recall of Merck & Co.'s painkiller Vioxx. Earlier this year, Representative Bart Stupak said that if Americans "knew how little the FDA did to assure the food and drug supply, if the truth ever came out...people would be marching in the street." Stupak—an eight-term Democratic congressman and chairman of the Subcommittee on Oversight and Investigations of the House's powerful Energy and Commerce panel, which has jurisdiction over the FDA—is at the center of an aggressive effort by congressional Democrats to spotlight what they say are problems with the Bush administration's position on consumer-safety issues. Stupak called for the resignation of von Eschenbach and other top officials.

Representative John D. Dingell, Democrat-Michigan and chairman of the House Energy and Commerce Committee, has long been unhappy with the U.S. Food and Drug Administration (FDA) and its commissioner, Andrew von Eschenbach. Dingell recently accused von Eschenbach of not doing his job and has repeatedly asked the FDA chief how much it would cost to do more inspections. The commissioner still has not provided specifics.

Dingell and other lawmakers said the FDA must conduct more inspections of companies sending drugs to the U.S. to ensure they are safe. “You cannot do your job, you are not doing your job,'' Dingell told von Eschenbach, who was a witness at the hearing before the energy and commerce panel's investigations subcommittee. “You simply are absolutely incapable of addressing your responsibilities.''

FDA Considering Biomarkers As a Way to Improve Drug Safety

Thu, 17 Apr 2008 00:00:00 -0700

A new way of testing experimental drugs is being considered by the Food & Drug Administration (FDA). If adopted, the FDA could end up requiring "biomarker" tests for all new drugs. Proponents of the new biomarker process say it would help bring new drugs to market more quickly, while at the same time, reduce the risk that patients might be exposed to dangerous side effects that aren't apparent when new drugs are tested in animals. However, some patient advocates, while favoring the adoption of biomarker tests, say they will only be useful if drug makers take their results seriously. In the past, several high profile drugs - for example Avandia and Vytorin - showed signs of toxicity in animal tests. But those problems were ignored and the drugs proceeded to human clinical trials, and were eventually approved by the FDA.

A biomarker is an indicator that can be used to test a biological function. Some biomarkers turn up when organs are injured and cells within the damaged tissue release substances into the blood, urine or saliva. These substances can be used to detect dangerous side effects. Right now, the FDA is considering a testing process that uses seven indicators - known as biomarkers - that signal kidney injury when found in the urine of test subjects. Initially, the seven biomarker testing processes will be qualified by the FDA for use in preclinical animal studies, and only as a complement to current tests. But ultimately, the pharmaceutical industry would like to see the FDA adopt a range of such biomarker tests for human clinical trials that would signal dangerous side effects like heart failure, liver damage or cancer.

Under current testing protocols, experimental drugs are subjected to animal testing before they can move on to human clinical trials. But animal tests aren't always the best predictor of whether substances will be safe for humans. For example, if a drug toxic to the kidneys passes animal tests today, the damage might not show up until it is too late. Under a biomarker protocol, samples of blood, urine or saliva, would be taken from participants in a clinical trial. If certain biomarkers indicated the patient was at risk, the trial could be stopped before any major damage occurs.

It is hoped that biomarkers will speed the development of new drugs. Over the past 10 years, the number of new drugs and therapies submitted for FDA approval dropped by 50 percent. The move towards biomarkers has also been spurred by safety scandals surrounding some drugs, such as Vioxx, which was found to put users at risk for heart attacks and strokes after it came on the market.

While many patient advocates agree that biomarkers could go a long way towards improving drug safety, they contend the process will only work if drug makers abide by results. And some are skeptical that this will always be the case. Dr. Sidney Wolf of the group Public Citizen told the "San Francisco Chronicle" that in the past, drug makers have ignored safety issues apparent in early testing of drugs. "Findings of toxicity in the currently required animal tests are not taken seriously enough by companies or by the FDA," Wolfe said. "Avandia showed evidence of heart damage in animal studies and, for Vytorin, tests showed serious toxicity in laboratory animals, regardless of how low a dose of this combination drug was used." Both drugs came under fire in the last year because of problems, and the companies that developed them have been accused of withholding or downplaying vital information on safety and effectiveness when they were submitted to the FDA for approval.

Unfortunately, it is not unusual for drug makers to use the control they have over drug clinical trials to downplay disturbing findings. Yesterday, two reports in the “Journal of the American Medical Association” (JAMA) found Merck Inc. concealed mortality risks in two key Vioxx studies, and hired “ghostwriters” to author research that was supposedly conducted by independent scientists. Such practices are used throughout the drug industry, though they are hard to document, the authors of the JAMA reports said. Considering this history, it is fair to question whether or not the pharmaceutical companies would attempt to manipulate biomarker tests in the same way.

Vytorin Investigation Focuses on Minutes of November Meeting

Mon, 14 Apr 2008 00:00:00 -0700

Lawmakers probing Vytorin have discovered that Merck and Schering-Plough had minutes of a key meeting about the drug written weeks after the event actually took place. Documents released by the House of Representatives Energy and Commerce Committee indicate at least one participant in that meeting raised concerns that those minutes did not accurately reflect what took place. Specifically, the minutes indicate that a panel of ad-hoc experts who attended the meeting agreed that the endpoint of the ENHANCE study should be changed. But emails from one attendee to a company scientist indicate that narrative may be false.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration (FDA) in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. Last month, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Documents obtained by the House of Representatives Energy and Commerce Committee show that Merck and Schering-Plough held a meeting to discuss ENHANCE on November 16, 2007. On December 19 - one week after Congress started investigating Vytorin - minutes for the meeting were circulated. According to The Wall Street Journal, the minutes suggest that at the November meeting, outside consultants had recommended that the companies make a critical change in the ENHANCE study's primary endpoint -- the main measure for how the drug would be evaluated.

But other documents released by the Congressional Committee dispute the minutes. After receiving the minutes, James Stein, a cardiac-imaging expert at the University of Wisconsin who was present at the November meeting, wrote in an email to a Schering-Plough scientist: "It was my understanding that there were no minutes or transcript of this meeting." He also told a company scientist in an email: "We did not vote on this....It was the decision of the company to change the endpoint."

It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study. The companies dropped their attempt to change the ENHANCE endpoint shortly thereafter.

According to The Wall Street Journal, Rep. John Dingell (D-Mich.) chairman of the House Energy and Commerce Committee, and Rep. Bart Stupak (D-Mich.) chairman of the Subcommittee for Oversight, sent a letter to Merck and Schering-Plough on Friday asking why minutes of the November meeting were "created after the fact" in December.

A Schering-Plough spokesperson told the Journal that only notes were taken at that meeting, and the minutes eventually were produced after the FDA requested them.

FDA Official Says Agency Won't Take Sides on Vytorin - Then Defends Vytorin

Fri, 11 Apr 2008 00:00:00 -0700

Criticism of Vytorin is unfair, a Food & Drug Administration (FDA) official said this week. However, CDER director Janet Woodcock said the FDA wouldn't be wading into the Vytorin debate anytime soon for fear of appearing "defensive". Still Woodcock said in an interview that the FDA continues to consider Vytorin an effective means of heart disease prevention because it effectively lowered LDL - or bad - cholesterol. This despite the fact that a recent study showed Vytorin was no better at preventing clogged arteries than cheaper statin drugs. Furthermore, Woodcock's assertions contradict those of a panel of prominent cardiologists who last month said Vytorin should only be used as a last resort.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the FDA in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. Last month, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology (ACC). A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

But Woodcock, who after stating in a recent interview that the FDA wouldn't be taking sides, said during the same interview that Vytorin is being treated unfairly, and the media is hyping its problems. “I believe people are piling on right now on one side of the argument. Independent reporters and media, if they really want to have some reasoned approach, ought to step back from that. But what we see right now is everybody just piling on to the same message," Woodcock told the news site FDA Webview. “What happens with these is that there is some little point that the scientists are arguing about, and then the media get on it, and they start throwing the baby out with the bathwater.”

But the cardiologists sitting on the ACC panel weren't members of the media, and its hard to see how their concerns about Vytorin could be overblown. And right now, it appears the recommendations of the ACC panel are resonating with physicians. According to the website FiercePharma, a Deutsche Bank analyst surveyed primary care doctors and found that 75 percent expect usage of Vytorin and its sister drug Zetia will drop in their practices. The analyst now predicts that market share for Vytorin will drop to 9 percent from 16 percent. Zetia, one of the drugs in the Vytorin combo, will see its share drop to 6 percent from 9.5 percent, the analyst concluded.

New Vytorin Orders Fall

Thu, 10 Apr 2008 00:00:00 -0700

New prescriptions for Vytorin were down last week, following last month's recommendations from some top cardiologists that Vytorin be used only as a last resort. That recommendation followed the release of the ENHANCE study that showed Vytorin worked no better than cheaper cholesterol medications.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE study, which was released on January 14, showed that Vytorin and Zetia were ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. Last month, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

According to Verispan, a drug data research firm, total U.S. Vytorin prescriptions for the week ended April 4 were flat with the week ended March 28, at about 306,000. However, new prescriptions written last week - as distinct from refills of older prescriptions - fell about 6% for Vytorin.

Prescriptions for Vytorin and Zetia had already been on the decline since mid- January, when ENHANCE was first released. It was thought prescription volume would recover, but those hopes have mainly been dashed since the calls for reduced usage made at the medical meeting March 30.

Already, Schering-Plough - where sales of Vytorin and its sister drug Zetia accounted for 60% of profits - is bracing for the hit its bottom line will sustain from the debacle. Last week, the company said it planned to cut costs by $1.5 billion by 2012. Roughly 5,500 employees will lose their jobs, or about 10 percent of the company’s workforce. Manufacturing plants will be shuttered and layers of middle and senior management slashed. Sales and marketing staff will also take cuts, as will R&D.

High Profile Drugs Turn Out to be Duds

Mon, 07 Apr 2008 00:00:00 -0700

Millions of Vytorin users recently learned that Vytorin and its component drug, Zetia, failed to work as initially expected. Final results of a clinical trial showed the drugs reduced LDL cholesterol, but failed to slow the buildup of artery-clogging plaque, thus suggesting they will do little or nothing to prevent heart attacks. “It hasn’t hurt my body, but apparently it hasn’t done any good either,” said C.W. MacLeod, a 57-year-old Texas businessman, who has spent about $100 a month in co-payments for a brand-name drug that doesn’t work.

“If lowering your cholesterol doesn’t reduce your risk, then what’s the point?” another Vytorin user wrote on an msnbc.com message board about the issue. “Maybe I’m dense, but I just don’t understand.” When MacLeod’s cholesterol shot up, he was thrilled to find a drug to bring it down, taking Vytorin for two years and believing his doctor’s assurance that as his "bad" cholesterol dropped, so would his risk of heart attack.

But, recently, some of the nation’s best-selling and most heavily promoted drugs have come under fire. The popular diabetes drug, Avandia, may raise the risk of heart attack; antidepressants may work no better than placebo; and top cancer drug, Avastin, may slow breast cancer, but does not impact overall survival. It’s a confusing situation for consumers who assume that widely used drugs are both safe and effective, said Fran Visco, president of the National Breast Cancer Coalition and a 20-year survivor of the disease. “You want drugs that save lives, that have a significant impact on the quality of life,” said Visco, whose agency helps patients make treatment decisions. “The drugs do not show these things.”

According to Dr. Harlan M. Krumholz, a professor of medicine at Yale University, the problems began in late 2006, when an increase in patient deaths halted development of torcetrapib, a promising cholesterol drug that boosted “good” HDL cholesterol. This was followed by Avandia, which raised questions about the benefits of lowering blood sugar, and later by Vytorin and Zetia, which challenged the benefits of lowering LDL cholesterol, Krumholz said. “It was a time to pause and say ‘Whoa,’’’ he said. “It has caused us to take a step back and say ‘How much do we really know?’”

Critics wonder if drugs are being released to market too soon and if—instead of relying on ultimate outcomes such as a reduction in heart attacks or strokes—many studies measure a drug’s effectiveness by using interim markers, such as lowered blood pressure. The Food and Drug Administration allows such markers because the cost is prohibitive when waiting for the results of large-scale outcome trials and the waits could possibly delay life-saving advances for millions, said Dr. Robert Temple, director of the agency’s office of medical policy. But the practice has been called into question, said Dr. Nortin M. Hadler, a professor of medicine at the University of North Carolina. “In our zeal to do modern medicine ... we’ve managed to lose our way,” he said. “We’ve forgotten to ask: ‘Does this matter to the patient?’”

UnitedHealth Group Says it Will Still Cover Vytorin

Fri, 04 Apr 2008 00:00:00 -0700

Vytorin coverage will not change for people enrolled in health plans provided by UnitedHealth Group. The nation's largest health insurer said it will continue paying for Vytorin, even though a recently released study showed it worked no better than cheaper statin drugs. Many health insurers have been reviewing their policies on Vytorin coverage because of that study - known as ENHANCE - and after a panel of prominent cardiologists recommended that Vytorin only be prescribed as a last resort for lowering cholesterol.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. But ENHANCE, which was released on January 14, showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

Over the weekend, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

The Vytorin controversy has caused many insurers to reconsider covering the expensive drug. One factor that could influence health plans is whether medical societies change their guidelines for cholesterol-drug use. On Tuesday, the head of the American College of Cardiology told Dow Jones that it will publish new guidelines in the next few months giving physicians advice on which patients should be given Vytorin in light of the ENHANCE findings.

One insurer, Cigna Corp,. has already suspended part of a program that notified members using certain other cholesterol drugs that Vytorin was an effective and less costly alternative. The program, known as “step therapy,” is an effort to help health plans control drug costs. Cigna said its suspension of Vytorin’s role in the step therapy program would last until a committee of experts could review the latest study to decide if permanent coverage changes were needed. In the meantime, Cigna will continue to pay for Vytorin prescriptions, and the insurer stressed that no one should discontinue any therapy without first talking to a doctor.

But UnitedHealth Group has decided to keep paying Vytorin for now. UnitedHealth Group charges the lowest co-payments for generics, including a version of Zocor, in insurance plans sold to patients enrolled in Medicare prescription plans. The second, more expensive pricing tier includes Vytorin and Lipitor from Pfizer.

A spokesperson for the insurer told the New York Times that the current Vytorin policy will continue. “There were no safety issues raised in January or now,” Brian Solow, medical director of clinical services at Prescription Solutions, UnitedHealth’s pharmacy group, said Wednesday. “The last thing we want to do is see patients stopping their medication when they need it.” UnitedHealth has not required patients to try an alternate cholesterol-lowering drug before Vytorin in the past and has no plans to do so at this time, Solow said.

The news that the nation's largest insurer is backing Vytorin is a rare bit o good news for the makers of Vytorin. According to The New York Times, Schering-Plough has lost $21 billion in market value since a preliminary report on the ENHANCE study was released in January. Since the recommendation of the American College of Cardiology recommendation, Schering-Plough has announced massive cutbacks that include laying off about 10 percent of its workforce and plant closures.

Insurers Taking Another Look at Vytorin Coverage

Wed, 02 Apr 2008 00:00:00 -0700

Insurers are said to be reconsidering coverage for Vytorin, after a study showed the cholesterol-lowering drug provided no added benefits over cheaper statins. Already, one large insurer has changed its approach to Vytorin coverage, and it is thought others will follow.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

But the ENHANCE, which was released on January 14, showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud. Over the weekend, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Now some insurers are considering following the panel's recommendation. Already, Cigna Corp. has suspended part of a program that notified members using certain other cholesterol drugs that Vytorin was an effective and less costly alternative. The program, known as "step therapy," is an effort to help health plans control drug costs. Under Cigna's step-therapy program, members can take "non-preferred" cholesterol drugs, but they have higher copays than "preferred" brands and generic drugs. Cigna said its suspension of Vytorin's role in the step therapy program would last until a committee of experts could review the latest study to decide if permanent coverage changes were needed. In the meantime, Cigna will continue to pay for Vytorin prescriptions, and the insurer stressed that no one should discontinue any therapy without first talking to a doctor.

Other insurers are also undertaking Vytorin reviews. An independent committee of experts that advises Medco Health Solutions Inc. on drug coverage policies "will be looking at the new data and be making recommendations on any changes" deemed necessary, Medco spokeswoman Ann Smith told Dow Jones Newswires. Another PBM, Express Scripts Inc., is reviewing the study, which the company says is standard practice whenever new drug data comes out. UnitedHealth Group Inc. one of the nation's largest health insurers, isn't making any immediate coverage changes for Vytorin, partly because medical guidelines haven't changed. But a committee will be reviewing the new data later this month.

One factor that could influence health plans is whether medical societies change their guidelines for cholesterol-drug use. On Tuesday, the head of the American College of Cardiology told Dow Jones that it will publish new guidelines in the next few months giving physicians advice on which patients should be given Vytorin in light of the ENHANCE findings.

Vytorin Emails Raise Questions About ENHANCE Delay

Tue, 01 Apr 2008 00:00:00 -0700

The Vytorin fallout continues, with one lawmaker demanding that Vytorin's makers explain why the results of a crucial study were delayed for more than a year. The request for more information on the delayed Vytorin study came just a day after a panel of prominent cardiologists recommended that Vytorin be used only as a last resort, because there is no evidence that the expensive medication provides any more benefits than a cheaper statin in preventing heart disease.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food and Drug Administration in 2004. Since it came on the market, Vytorin sales have reached $5 billion per year. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes. But ENHANCE, which was released on January 14, showed that Vytorin was ineffective in preventing clogged arteries, and might actually increase plaque in some users. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for more than a year – something critics of the company have likened to fraud.

Over the weekend, the full ENHANCE study was vetted during the annual meeting of the American College of Cardiology. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. “Our strongest recommendation is that people need to go back to statins,” said panel member Dr. Harlan Krumhotz.

Now, Senator Charles Grassley (R-Iowa) has sent a letter to Merck and Schering-Plough seeking more explanation on the delay in releasing ENHANCE. According to The Wall Street Journal, Sen. Grassley, a member of the Senate Finance Committee, is among several lawmakers probing whether the companies deliberately withheld negative information to protect sales of Vytorin and a sister drug Zetia. The companies have denied that and said they were trying to resolve issues with flaws in the data.

At issue are a series of emails between company executives and the ENHANCE study's lead researcher, John P. Kastelein of Academic Medical Center, Amsterdam, that indicate that Kastelein was upset with the companies decision to withhold ENHANCE from last November's America Heart Association meeting. Excerpts of the emails were released in Sen. Grassley's letter. "If this is true, [Schering-Plough] must have taken this decision without even the semblance of decency to consult me," Kastelein wrote in an email sent July 6. "I can tell you if this is the case, our collaboration is over. This starts smelling like extending the publication [of the study] for no other [than] political reasons and I cannot live with that."

Sen. Grassley's letter said the e-mails, supplied by the companies, indicated Schering-Plough and Merck may have delayed for more than a year releasing results ENHANCE, for "marketing purposes." Sen. Grassley also asked for details about payments made to researchers and doctors who promoted the Vytorin.

Vytorin Should be Considered a "Last Resort"

Mon, 31 Mar 2008 00:00:00 -0700

Vytorin should only be used as a last resort because there is no evidence that the cholesterol-lowering medication provides any more benefits than cheaper statins alone. That was the conclusion reached by a panel of four prominent cardiologists after the results of the much-delayed ENHANCE study were released at the American College of Cardiology meeting over the weekend. The study looked at whether Vytorin, which is a combination of Merck & Co.'s Zocor and Schering-Plough Corp.'s Zetia, was better at reducing clogged arteries in the neck than Zocor, a statin drug, alone.

The ENHANCE study, which was funded by Merck and Schering-Plough, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin, Zetia or a high dose of simvastatin, the generic form of Zocor. While both Vytorin and Zetia were found to have significantly reduced cholesterol in these patients, neither drug provided any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin or Zetia on the theory that the drugs would reduce this risk in people with high cholesterol. The ENHANCE study was a serious blow to this theory.

This Sunday, the full ENHANCE study was discussed at the American College of Cardiology's annual meeting. A panel of four doctors concluded that Vytorin should be used only as a last resort, considering that the expensive drug did not provide any added benefits. "Our strongest recommendation is that people need to go back to statins," said panel member Dr. Harlan Krumhotz. "We really think there's just a small group of patients who cannot get to target (cholesterol) on statins." He said doctors should maximize the doses of statins and then try adding other drugs such as niacin-based drugs or fibrates in an attempt to lower LDL cholesterol levels as current practice guidelines recommend. The doctors said that Vytorin shouldn't be widely used until a larger study proves whether the pill reduces the risk of heart attacks and deaths, the doctors said.

That study is now underway. On Friday, researchers from Brigham and Women's Hospital in Boston and Duke University in Durham, North Carolina said the trial - known as Improve-It - will be expanded by 80 percent to ensure it has enough patients to get a clear result. The 2 1/2 year study, originally intended to include at least 10,000 patients, will now follow 18,000 patients. Doctors are looking for a 10 percent reduction in complications like heart attacks and deaths. Improve-It, uses half the dose of Zocor, sold generically as simvastatin, in both groups.

Several doctors attending the weekend conference criticized Merck and Schering-Plough for not subjecting Vytorin to a large clinical trial until Vytorin had been on the market for some time, and was very widely prescribed. The companies have also been criticized for their handling of ENHANCE. The data from the ENHANCE trial was supposed to be released by March 2007, but that didn’t happen. Last November, the doctor who supervised the ENHANCE trial told the New York Times that the drug’s makers, who controlled the study’s raw data, blocked its release. In December, a congressional committee requested more information on the ENHANCE study. Merck and Schering-Plough maintained that the ENHANCE results were delayed because of the complexity of the data.

Merck and Schering-Plough also tried at one point to change the ENHANCE study’s endpoint. The endpoint is the main medical result the study was meant to measure, and it is generally accepted among scientists that for a clinical trial to be valid, the endpoint must never change. Following a great deal of outcry, Merck and Schering-Plough backed off changing the ENHANCE endpoint in December.

Vytorin Prescriptions Still Lag

Thu, 20 Mar 2008 00:00:00 -0700

Vytorin prescriptions have yet to recover from the dive they took in January, following the release of a study that showed the expensive cholesterol-lowering medication provides no more benefits than a cheaper statin. And Vytorin could take an even bigger hit later this month when that study, known as ENHANCE, is fully vetted at the annual meeting of the American College of Cardiology (ACC).

Vytorin is a combination of cholesterol lowering Zetia and the statin Zocor. The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin on the theory that the drug would reduce this risk in people with high cholesterol. Even though ENHANCE was finished in April 2006, Merck and Schering-Plough did not register ENHANCE with the Clinical Trials Database until October 2007 – and even then they did not register the results. In fact, Merck and Schering-Plough delayed releasing the ENHANCE results twice, and the data was only made public in early January. At one point, the companies even tried to change the study’s endpoint – the main medical result it was supposed to measure. But a public outcry and a congressional investigation kept that from happening.

Those revelations caused many in the medical community to question the wisdom of prescribing Vytorin, which costs about $3/pill, rather than high dose of a less expensive statin at about $1/pill. Among the new Vytorin critics was Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. Dr. Nissen told CBS News that he would advise doctors to quit prescribing Vytorin, since it was not shown to be more effective than Zocor. “My advice to physicians is not to use this drug Vytorin nor to use Zetia as first line agents any more. These should be really relegated to drugs of last resort until we have some evidence that they produce a health outcomes benefit,” he said. “Right now, five years into this, with nearly 1 million prescriptions per week being written, there is no evidence that the drugs actually produce any benefit for patients.”

Schering-Plough, which markets Vytorin in a joint venture with Merck & Co., disclosed Monday that total prescriptions for February were 2.8 million, versus 3.2 million in January for it and its sister drug, Zetia.

Later this month, results from ENHANCE will be featured in a "showcase" at the ACC conference, where scientists will present the results and a panel of experts will discuss them on March 31. The idea of the showcase is to present the information and discuss the trial and the trial design, what it shows and didn't show. Merck and Schering-Plough, analysts and investors will be closely watching the results of the ACC conference and measuring physician reaction to them to try to determine if they might enhance a rebound in sales or spell more trouble for Vytorin sales.

More Heat for Vytorin and Avandia

Wed, 05 Mar 2008 00:00:00 -0800

Avandia and Vytorin are the subject of yet another government investigation. The Government Accountability Office (GAO) will look into whether the US Food and Drug Administration’s (FDA) drug-review process cleared two popular medications without sufficient proof of their safety or effectiveness.

Senator Charles E. Grassley (Republican-Iowa) requested the GAO investigation after recent studies suggested that the diabetes pill Avandia increases the risk of cardiac problems in patients, and another study showed that the cholesterol drug Vytorin may not actually lower the risk of heart attack and artery-clogging plaque, as assumed by millions of patients and doctors. "There's enough of a pattern of problematic drugs to ask for an independent review of how the FDA follows up on the effects of medicines that it's approved," Grassley said. The question is whether the FDA should approve drugs based on biological measures, such as cholesterol and blood sugar, without evidence that they improve more meaningful measures, such as survival.

The makers of Vytorin have been named as defendants in a lawsuit filed by a New York man who took the defective drug based on the belief that it offered more protection from clogged arteries, heart attacks and strokes than other, less expensive statin drugs. Sigmond Tomaszewski, who began taking Vytorin in January 2007, alleges that Merck and Schering-Plough knew in April 2006 that Vytorin was ineffective at reducing artery clogging plaque, heart attacks and strokes, but purposely kept that information from the public and the medical community.

Lawsuits against GlaxoSmithKline over the diabetes drug Avandia are emerging and many more are expected. One a man is suing GlaxoSmithKline in federal court, claiming Avandia caused him to undergo heart bypass surgery. Attorneys allege the drug maker should have known that Avandia—prescribed to improve blood sugar in type 2 diabetes patients—is linked to a significant and increased risk of heart failure, heart attack, and stroke.

The FDA refuses to withdraw Avandia from the market, but has asked Glaxo to conduct a long-term study comparing Avandia with other type 2 diabetes drugs. The trial will likely commence in a year; however, full results are not expected until 2014. Patient advocates and FDA critics consider the recent black box warning—the strongest warning for a drug—for Avandia a feeble response to Avandia’s safety issues, and have requested it be pulled from the market. Meanwhile, the American Diabetes Association and the European Association for the Study of Diabetes released a revised consensus statement stating that emerging information suggests additional hazards associated Avandia and may result in increased risk of myocardial infarctions. The US Department of Veterans Affairs announced it was dropping Avandia from its drug formulary because, in some, Avandia did not afford the same margin of safety as other diabetes drugs. A Congressional Committee Report found Glaxo executives intimidated a diabetes expert into
keeping quiet about Avandia’s safety problems.

Vytorin Prescriptions Down Again After Brief Reprieve

Wed, 20 Feb 2008 00:00:00 -0800

Vytorin prescriptions have fallen again, dashing hopes at Merck and Schering-Plough that the fallout from a disappointing Vytorin study was starting to ebb. Vytorin prescriptions had fallen immediately after the release of the ENHANCE study on January 14, but had appeared to rebound the past few weeks. Today’s news that Vytorin prescriptions are down again indicate that the drug makers’ have a long way to go to repair the damage wrought by ENHANCE

Vytorin is a combination of cholesterol lowering Zetia and the statin Zocor. The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin on the theory that the drug would reduce this risk in people with high cholesterol. The ENHANCE study is a serious blow to this theory.

Those revelations caused many in the medical community to question the wisdom of prescribing Vytorin, which costs about $3/pill, rather than high dose of a less expensive statin at about $1/pill. Among the new Vytorin critics was Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. Dr. Nissen told CBS News that he would advise doctors to quit prescribing Vytorin, since it was not shown to be more effective than Zocor. “My advice to physicians is not to use this drug Vytorin nor to use Zetia as first line agents any more. These should be really relegated to drugs of last resort until we have some evidence that they produce a health outcomes benefit,” he said. “Right now, five years into this, with nearly 1 million prescriptions per week being written, there is no evidence that the drugs actually produce any benefit for patients.”

Immediately following the release of ENHANCE, Vytorin prescriptions fell by about 9.5%. According to the Wall Street Journal, they then started to recover as the Merck and Schering-Plough stepped up efforts to persuade doctors to resume prescribing them as they had before. In an earnings call last week, Schering-Plough CEO Fred Hassan voiced his support for Vytorin, saying, “The doctors generally knew that this was one of those media-driven situations.”

But Hassan may have spoken too soon. According to the Wall Street Journal, Vytorin prescriptions for the week ended February 15 were off 7% to 327,698 compared with the previous week. And the prescriptions were down nearly 18% from the week preceding the release of the study results on January 14.

The precipitous fall of Vytorin prescription likely has more to do with the fact that the drug offers no additional benefits compared to cheaper statins than it does with media hype. It’s understandable that patients would not want to pay a premium for Vytorin when less expensive alternatives are available. Unfortunately, for Merck and Schering-Plough, that reality is not “media-driven.”

Vytorin Revelations Lead to Cholesterol Debate

Tue, 05 Feb 2008 00:00:00 -0800

The Vytorin debacle has sparked some in the medical community to reassess the importance of controlling LDL – so-called bad –cholesterol in preventing heart and coronary artery disease. It has long been accepted that reducing LDL cholesterol would prevent the build-up of artery clogging plaque. But a study released last month that indicated that Vytorin did nothing to prevent plaque buildup has raised doubts about that theory. The new debate sparked by the Vytorin revelations could have serious implications for the millions of people who use other cholesterol lowering drugs, including statins.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the Food & Drug Administration in 2004. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels are thought to put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

The ENHANCE study, which began in June 2002, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. The ENHANCE study found that Vytorin worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone. In fact, some of the Vytorin patients in ENHANCE actually developed more arterial plaque than those taking Zocor alone, putting them at an even greater risk of heart attacks and strokes.

As a result of the ENHANCE study, some of the world's leading heart doctors have begun to question whether the lower-is-better theory of cholesterol management still holds. But ENHANCE was not the first study to do spark such doubts. Studies of the experimental Pfizer drug torcetrapib had earlier called the theory into question. Torcetrapib represented a new class of cholesterol medicine designed not only to lower LDL cholesterol but also to boost HDL, or "good" cholesterol. But the results of two large-scale studies linked torcetrapib to deaths and showed it failed to prevent the buildup of arterial plaque. Soon after, Pfizer gave up on the drug.

No one is suggesting that cholesterol-lowering medicines be abandoned, but many are now questioning whether the pharmaceutical industry's longtime focus on bad cholesterol is fully supported by scientific evidence.

Vytorin Lawsuits Keep Coming

Mon, 04 Feb 2008 00:00:00 -0800

Vytorin makers Merck and Schering-Plough are facing yet another lawsuit, this time from the plaintiffs in Nevada. The Nevada Vytorin consumer fraud lawsuit alleges that Merck and Schering-Plough deceived heart patients in that state by leading them to believe that Vytorin was more effective than a cheaper generic statin. The makers of the beleaguered cholesterol drug face similar lawsuits in several states, including California, Florida, New York and Ohio.

Merck and Schering-Plough’s Vytorin troubles started on Jan. 14, when the companies released the long-awaited results of the ENHANCE study. The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor.

Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck. What’s worse, instead of clearing plaque from artery walls, Vytorin appears to have led to, or at least allowed, a thickening of that plaque.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin on the theory that the drug would reduce this risk in people with high cholesterol. The ENHANCE study is a serious blow to this theory.

Even though ENHANCE was finished in April 2006, Merck and Schering-Plough did not register ENHANCE with the Clinical Trials Database until October 2007 – and even then they did not register the results. In fact, Merck and Schering-Plough delayed releasing the ENHANCE results twice, and the data was only made public in early January. At one point, the companies even tried to change the study’s endpoint – the main medical result it was supposed to measure. But a public outcry and a congressional investigation kept that from happening.

Lawyers involved in the Nevada Vytorin lawsuit assert that the nearly two year delay in releasing ENHANCE constitutes fraud, as do the lawsuits filed in other states. Many of the Vytorin lawsuits seek to recoup the difference in cost between generic cholesterol drugs that cost about one-third as much as Vytorin.

Unfortunately for Merck and Schering-Plough, plaintiffs’ attorneys are not the only ones looking into the Vytorin debacle. Several state attorneys general have started their own probes that could eventually lead to civil and/or criminal penalties. Last week, the Connecticut Attorney General’s Office announced it was investigating Merck and Schering-Plough to see if “state funds were spent on false assurances about the safety and effectiveness of” Vytorin and Zetia. New York Attorney General Andrew Cuomo wants to know if Merck and Schering-Plough purposely withheld the results of ENHANCE in an effort to protect sales of Vytorin. Cuomo has also questioned the timing of stock sales made by company executives prior to the release of ENHANCE. Vytorin is also the subject of several investigations in the US Congress.

Vytorin in Connecticut Crosshairs

Tue, 29 Jan 2008 00:00:00 -0800

Connecticut can now be added to the list of states investigating Vytorin. According to The Wall Street Journal, Connecticut Attorney General Richard Blumenthal announced that his office investigating Merck and Schering-Plough for claims the companies made about Vytorin. Over the weekend, New York State Attorney General Andrew Cuomo announced a similar Vytorin investigation, and several congressional committees are also investigating the drug makers. Vytorin has been under intense scrutiny since a study, known as ENHANCE, was released earlier this month showing the cholesterol lowering drug was no more effective at preventing clogged arteries than a cheaper, generically available statin.

Vytorin is a combination of cholesterol lowering Zetia and the statin Zocor. The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

The ENHANCE study was supposed to have been released by Merck & Schering-Plough in November 2006, but that was delayed by the companies until March 2007. Then Merck and Schering-Plough announced the release of ENHANCE would be delayed again until March 2008. The drug makers also announced that they would be changing the ENHANCE study’s endpoint – the main medical result the study was meant to measure. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study.

According to the Wall Street Journal, the Connecticut Attorney General is investigating Merck and Schering-Plough to see if “state funds were spent on false assurances about the safety and effectiveness of” Vytorin and Zetia. Blumenthal said Connecticut’s Medicaid program was the main public source of money spent on the medications.

The Wall Street Journal was told by a Merck spokesperson that the company hadn't been notified of an investigation by Connecticut but will cooperate. "We stand by the safety and efficacy profiles of both Zetia and Vytorin," the spokesperson said. "We acted with integrity and good faith in connection with the clinical trial."

Many Vytorin users apparently disagree with Merck’s assertion that it acted in “good faith” in regards to Vytorin. At least five class action lawsuits have been filed against Merck and Schering-Plough since the ENHANCE results made news, with many of them asserting that the companies’ decision to delay its release for nearly two years was an act of fraud.

Vytorin Mess Attracts Attention of New York Attorney General

Mon, 28 Jan 2008 00:00:00 -0800

The Vytorin mess seems to be getting worse for Merck and Schering-Plough. Already facing a firestorm over its handling of the so-called ENHANCE study that found Vytorin worked no better than cheaper generic statins, the companies now face a subpoena from the New York State Attorney General’s office. Andrew Cuomo wants to know if Merck and Schering-Plough purposely withheld the results of ENHANCE in an effort to protect sales of Vytorin. The attorney general has also questioned the timing of stock sales made by company executives prior to the release of ENHANCE.

But the ENHANCE study finding that Vytorin was in fact not effective in reducing arterial plaque was completed in April 2006. ENHANCE, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. The ENHANCE study found that Vytorin worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone. In fact, some of the Vytorin patients in ENHANCE actually developed more arterial plaque than those taking Zocor alone, putting them at an even greater risk of heart attacks and strokes. In spite of the findings, Merck and Schering-Plough delayed releasing ENHANCE for nearly 2 years – something critics of the company have likened to fraud.

According to an email released by the New York Attorney General’s office on Saturday, the state’s Vytorin investigation focuses on the marketing of the drug. "We will investigate and, when appropriate, hold accountable drug companies for engaging in irresponsible and deceptive conduct and any deceitful marketing of prescription drugs," Cuomo said in the statement. "Drug companies are on notice that concealing critical information about life-saving prescription drugs, profiting at the expense of patients' health, and wasting taxpayer dollars, is simply unacceptable."

The attorney general also sought information to determine whether insider sales of stock were appropriate and whether statements to investors were accurate. According to Bloomberg.com, Carrie Smith Cox, a Schering-Plough executive vice president, sold 900,000 shares for $28 million on April 20, according to a Securities and Exchange Commission filing. No reference to her was made in yesterday's statement.

On its website, Schering-Plough reiterated that executives followed rigorous processes to ensure they complied with federal securities laws in trading company stock. Among these are that executive officers must pre-clear every transaction in company shares with one of the company's securities lawyers. The companies maintain that top executives were only made aware of the ENHANCE findings days before they were made public.

Vytorin Latest Drug Scandal to Raise Questions about FDA Oversight

Fri, 25 Jan 2008 00:00:00 -0800

The Vytorin controversy has once again raised serious questions about the way the Food & Drug Administration (FDA) approves new drugs. At issue is the agency’s policy to allow drug clinical trials to measure only “proxy markers” and not the true outcome that the medication is supposed to provide.

According to The Wall Street Journal, a proxy measure is a clinical stand-in for a drug's broader and more important effect on the body. For example, the FDA approved Vytorin based on clinical trials that measured cholesterol reduction. It was believed that cholesterol reduction was an adequate proxy marker for reducing clogged arteries and heart attacks.

According to The Wall Street Journal, the rationale behind the use of such proxy markers is that they allow for shorter clinical trials, thereby lessening costs for drug makers. They also allow drugs to come to market quicker.   Defenders of proxy markers point out that many life-saving AIDS drugs would never have been approved without the use of proxy markers.

But proxy markers are not always an accurate measure of a more important outcome.   In the case of Vytorin, lower cholesterol did not translate into less artery clogging plaque. In the case of another drug, Avandia, clinical trials that measured only blood sugar reduction did not make it apparent that the diabetes drug carried significant cardiac side effects that outweighed its benefits.

To measure whether or not Vytorin really did reduce artery clogging plaque in the carotid artery, Merck and Schering-Plough designed the ENHANCE study. Vytorin is a combination of cholesterol lowering Zetia and the statin Zocor.   The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor.   Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

ENHANCE was finished in April 2006, but was delayed twice before Merck and Schering-Plough finally released its results in a press release on January 14. The nearly-two year delay in revealing that Vytorin was no better than a placebo has angered many, and sparked numerous Vytorin lawsuits, as well as a congressional investigation.

The Vytorin debacle has also caused criticism of the FDA policy that allows proxy markers. But eliminating the use of proxy markers would add to the cost of drug development and delay release of important lifesaving medications.

Some experts who spoke to The Wall Street Journal did not favor ending the use of proxy markers, but do want to see the FDA require follow up studies that measure the truly desired endpoint, and tight timelines for starting, completing and releasing data from such studies. “The FDA needs to have more teeth,” John Buse, a professor at the University of North Carolina, and a frequent critic of Avandia told the Wall Street Journal. “They need to demand hard endpoint studies at the time of approval and they need to have some system for monitoring progress."

Other sources interviewed for the Journal article agreed, and went even further, saying that drug makers should face marketing restrictions until a medications’ desired endpoint has been proven. One suggested that direct-to-consumer advertising shouldn't be permitted until those results are in. That expert also felt prescribing information, or labels, for such medicines should clearly reflect the uncertainty of the long-term benefit until the data are in.

FDA Issues Vytorin Early Communication

Fri, 25 Jan 2008 00:00:00 -0800

The Food & Drug Administration (FDA) weighed in on the Vytorin controversy today by issuing an Early Communication about its ongoing reviews of Vytorin, Zetia and Zocor. The FDA communication was prompted by preliminary results of the ENHANCE study that showed Vytorin was no better at preventing plaque buildup of the arteries in the neck than a statin alone.

Vytorin, which was developed and marketed jointly by Merck and Schering-Plough, was approved for use by the FDA in 2004. Vytorin is a combination of cholesterol-lowering Zetia and the statin Zocor. Statins like Zocor reduce the amount of cholesterol produced by the liver, while Zetia lessens the amount of cholesterol in food that is absorbed in the intestines. High cholesterol levels put a person at risk of developing clogged arteries – a major risk factor for heart attacks and strokes. Doctors and Vytorin users were led to believe that the drug would effectively reduce both sources of cholesterol, thereby lessening the amount of plaque build up in the arteries, as well as the risk of having heart attacks and strokes.

The ENHANCE study, which began in June 2002, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. The ENHANCE study found that Vytorin worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone. In fact, some of the Vytorin patients in ENHANCE actually developed more arterial plaque than those taking Zocor alone, putting them at an even greater risk of heart attacks and strokes.

The ENHANCE study was supposed to have been released by Merck & Schering-Plough in November 2006, but that was delayed by the companies until March 2007. Then Merck and Schering-Plough announced the release of ENHANCE would be delayed again until March 2008. The drug makers also announced that they would be changing the ENHANCE study’s endpoint – the main medical result the study was meant to measure. It is generally accepted that for a clinical trial to be effective, a study’s endpoint must be set at its beginning and remain unchanged. In December 2007, in response to the ENHANCE delays and the attempt by Merck and Schering-Plough to change the endpoint, Congress initiated an investigation of the ENHANCE study.

Merck and Schering-Plough backed off changing the ENHANCE endpoint and released the preliminary results of the study on January 14 in the form of a press release. The FDA said that once Merck and Schering-Plough complete the analysis of the unblinded data from ENHANCE, the companies will submit a final study report to FDA. From that point, it should take the FDA approximately 6 months to fully evaluate the data. After reviewing the data from the ENHANCE study, and considering all other available information about the link between cholesterol lowering and reduction of clogged arteries and cardiovascular events, the FDA will determine whether any further regulatory action is warranted with regard to Zetia and Vytorin. The FDA also said that once it finished its own review, it would consider whether any changes to its current approach to cholesterol-lowering drugs was warranted.

In spite of the fact that ENHANCE found that Vytorin was no more effective than a high dose of generically-available Zocor, the FDA said it was not advising healthcare professionals to stop prescribing the drug.

Vytorin Support Statement Raises Questions Over American Heart Association Funding

Thu, 24 Jan 2008 00:00:00 -0800

Vytorin appears to have an important ally.   One day after news broke that a study had shown Vytorin to be ineffective in preventing clogged arteries, the American Heart Association rushed to the drug’s defense. But the American Heart Association’s statement supporting Vytorin left out one important fact – the organization receives substantial financial support from Vytorin makers Merck and Schering-Plough.   The revelation has led some to question the American Heart Association’s relationship with the pharmaceutical industry.

Vytorin is a combination of cholesterol lowering Zetia and the statin Zocor.   The point of the ENHANCE study was to determine how well Vytorin prevented clogged arteries by reducing the formation of plaque. ENHANCE focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor.   Vytorin did not provide any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin on the theory that the drug would reduce this risk in people with high cholesterol. The ENHANCE study was a serious blow to this theory.

But the American Heart Association says Vytorin is still a good bet. In a statement issued on Jan. 15, the day after the report’s release, the heart association said the study was too limited to draw conclusions about Vytorin’s ability to reduce heart attacks or deaths compared to Zocor alone. The group advised patients not to abruptly stop taking it without consulting their doctors.   There was no mention of the $2 million per year contribution that Merck and Schering-Plough makes to the American Heart Association. Dr. Daniel W. Jones, the president of the American Heart Association, who was quoted in the Vytorin support statement, told the New York Times on Wednesday that his group did not typically mention its drug company sponsors when issuing news releases with advice to patients.

Lots of people think the American Heart Association should have noted Merck and Schering-Plough’s financial support. Among the critics are several law makers. According to the New York Times, the House Energy and Commerce Committee today sent letters to the American Heart Association and Merck/Schering-Plough asking about their relationship.

The American Heart Association isn’t the only organization to have received cash from the Vytorin makers. The American College of Cardiology, a much smaller group, also receives drug industry money and also released a statement last week advising patients not to stop taking Vytorin without consulting their doctors. The American College of Cardiology is also going to be hearing from the House Energy and Commerce Committee.

Both organizations told The New York Times on Wednesday that the industry financing had nothing to do with their statements, which they said they issued in response to public confusion about the meaning of the Vytorin study. Merck and Schering-Plough also said it had played no role in the statements by the two groups. But many people are finding it hard to believe that the drug maker’s gave away millions without expecting anything in return.

Vytorin Lawyer Side Effects Attorney Clogged Arteries Lawsuit Injury Heart Attack Stroke

Thu, 24 Jan 2008 00:00:00 -0800

Vytorin Fails to Prevent Clogged Arteries

Keywords: Vytorin | Lawyer | Side | Attorney | Effects | Clogged | Arteries | Lawsuit | Injury | Heart Attack | Stroke

On January 14, 2008, the results of a long-awaited study on the effectiveness of Vytorin to reduce artery clogging plaque in patients with high cholesterol were released. The ENHANCE study found that Vytorin, a combination of cholesterol lowering Zetia and the statin Zocor, worked no better to reduce clogged arteries than a high dose of a less-expensive, generically available statin alone.

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Vytorin
Vytorin, developed and marketed jointly by Merck and Schering-Plough, is a combination of cholesterol-lowering Zetia and the statin Zocor. Vytorin was approved by the Food & Drug Administration in 2004 to treat both sources of cholesterol - absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues. It was believed that the treatment of cholesterol from both sources would likely to result in lower cholesterol levels. It was likewise theorized that this reduction in cholesterol would in turn reduce the amount of plaque buildup in the arteries, thus reducing the risk of heart attack and stroke. However, the results of the ENHANCE study showed that Vytorin brought about no measurable reduction in the amount of artery plaque buildup.

The ENHANCE Study
The ENHANCE study, which was funded by Merck and Schering-Plough, focused on a group of 720 patients with a rare condition predisposing them to high cholesterol. The patients were given either Vytorin or a high dose of simvastatin, the generic form of Zocor. While both Vytorin and Zetia were found to have significantly reduced cholesterol in these patients, neither drug provided any significant benefit versus the statin drug Zocor in slowing down clogging of the arteries. Overall, the study failed to meet its primary goal, which was to show whether Vytorin was more effective than Zocor alone in preventing progression of atherosclerosis in the carotid artery, which is in the neck.

Such plaque buildup is a major risk factor for heart attacks and stroke. Many doctors had been prescribing Vytorin or Zetia on the theory that the drugs would reduce this risk in people with high cholesterol. The ENHANCE study was a serious blow to this theory.

There is some evidence that Merck and Schering-Plough tried to suppress the ENHANCE studies findings. The data from the ENHANCE trial was supposed to be released by March 2007, but that didn’t happen. In November 2007, the doctor who supervised the ENHANCE trial told the New York Times that the drug’s’ makers, who controlled the study’s raw data, blocked its release. In December, a congressional committee requested more information on the ENHA NCE study. Merck and Schering-Plough maintained that the ENHANCE results were delayed because of the complexity of the data.

According to the New York Times, Merck and Schering-Plough also tried at one point to change the ENHANCE study’s endpoint. The endpoint is the main medical result the study was meant to measure, and it is generally accepted among scientists that for a clinical trial to be valid, the endpoint must never change. Following a great deal of outcry, Merck and Schering-Plough backed off changing the ENHANCE endpoint in December.

It is understandable that Merck and Schering-Plough would have wanted to delay the disappointing results of the ENHANCE study. Combined Vytorin and Zetia sales were about $3.7 billion for the nine months ended Sept. 30, up 33% from the year-earlier period. The disappointing results of ENHANCE put those sales at risk, as many doctors may opt to prescribe the generic version of the Zocor alone, rather than the combo pill Vytorin. Generic versions of Zocor cost roughly $1 per pill, compared with about $3 per Vytorin tablet.

Legal Help
If you or a loved one used Vytorin under the assumption that it would reduce the risk of clogged arteries, heart attack and stroke, you may have valuable legal rights. Please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney

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Vytorin Fails to Prevent Clogged Arteries

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