Yourlawyer.com (Procrit News)

Procrit, Similar Drugs Linked to Increased Death Risk By Two More Studies

Tue, 05 May 2009 00:00:00 -0700

Two more studies have found that anemia drugs like Epogen, Procrit and Aranesp raise the risk of death among cancer patients. Despite known safety risks, drugs like Procrit continue to be used because it is believed that they help reduce the number of blood transfusions some cancer patients need, while improving quality of life. According to a report on MedicineNet.com, these two studies may raise questions about that theory.

Epogen, Procrit and Aranesp are known as erythropoiesis-stimulating agents (ESAs). ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. They are approved in the U.S. to treat anemia in cancer patients undergoing chemotherapy.

ESAs have long been the subject of safety concerns. Last summer, the Food & Drug Administration (FDA) ordered the labeling changes because several studies have shown that Procrit and other ESAs increased tumor growth and shortened survival time in some cancer patients. Among other things, the agency mandated that the labeling be modified to say that the drugs shouldn’t be used in cancer patients receiving chemotherapy when a cure of their cancer is anticipated.

In the first study, researchers from the University of Alberta, Canada, analyzed data from 52 clinical trials that included more than 12,000 people. According to MedicineNet.com, they found that patients treated with ESAs increased the risk of death and serious adverse events such as blood clots by 15% to 16%.

The report, published in the April 30 online edition of the Canadian Medical Association Journal, concluded that ESAs should not routinely be used as an alternative to blood transfusions in patients with anemia related to cancer.

The second study, published in the May 2 issue of The Lancet, was conducted by scientists at the University of Bern in Switzerland. They looked at the findings from 53 cancer trials that included a total of almost 14,000 patients. More than 1,500 patients died during the study period, and almost 5,000 patients died overall, MediciNet.com said. That translated to a 17% increase in deaths during the study period. Patients undergoing chemotherapy had a 10% increased risk of dying.

The authors wrote that the findings "show that erythropoiesis-stimulating agents increase mortality in all patients with cancer, and a similar increase might exist in patients on chemotherapy." They advised that the risks of ESA be balanced against the benefits of treatment. They also said more study is needed to address the drugs' impact on tumor progression and quality of life, MedicineNet.com said.

FDA Investigating Procrit and Epogen Following Clinical Trial Deaths

Fri, 26 Sep 2008 00:00:00 -0700

Epoetin alfa, an anemia drug sold in the U.S. as Procrit and Epogen, is being reviewed by federal regulators after patients in a German stroke study treated with the drug died at a higher rate than those administered a placebo. The Food & Drug Administration (FDA) said it will be receiving more data about the German epoetin alfa trial in the next several weeks. Once that data has been analyzed, the FDA will communicate its conclusions and recommendations regarding this drug to the public.

Procrit and Epogen are known as erythropoiesis-stimulating agent (ESA). They are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. Procrit and Epogen are approved in the U.S. to treat anemia in cancer patients undergoing chemotherapy.

The German study involved a version of epoetin alfa called Eprex, made by Johnson & Johnson, which is not marketed in the U.S. According to the FDA, Johnson & Johnson made it aware of preliminary safety findings from a clinical trial conducted in Germany investigating the use of epoetin alfa to treat acute ischemic stroke. Treatment of anemia was not a goal of the trial and most patients were not anemic.

According to the FDA, the clinical trial was a double-blind, placebo-controlled, multicenter investigation in 522 adult patients with an MRI-confirmed ischemic stroke in the area of the middle cerebral artery. Patients were randomized to either receive treatment with a placebo or epoetin alfa administered as an intravenous dose of 40,000 units - a relatively high dose - daily for three days. R-tPA, a medication used to help dissolve blood clots, and often used for acute strokes, was also used when clinically indicated. The FDA said the goal of the clinical trial was to determine whether a high dose of epoetin alfa administered for three days would improve the ability of patients to care for themselves after their strokes.

Over a period of ninety days after the start of the trial, 16 percent of the patients who received epoetin alfa died, compared to only 9 percent of patients in the placebo group. Roughly half of all deaths in both groups occurred within the first seven days after starting the drug, with death from intracranial hemorrhage (bleeding within the brain) occurring among approximately 4 percent of epoetin alfa patients compared to 1 percent of patients in the placebo group.

The FDA said that it is aware of other clinical trials investigating the use of epoetin alfa to improve the functional outcomes of patients after stroke. The agency said that the finding of increased mortality in patients receiving epoetin alfa in the German trial suggests the need to closely monitor patients enrolled in these trials for adverse outcomes and to evaluate whether the potential benefits for enrolled patients outweigh the risks in these trials.

The FDA will work with the manufacturers of ESAs and other sponsors of clinical studies to evaluate the risks and benefits associated with the investigational uses of these ESA products as potential “neuroprotective agents.”

Amgen Ends Controversial Aranesp Marketing Practices

Fri, 29 Aug 2008 00:00:00 -0700

The maker of Aranesp is halting marketing practices that critics said encouraged over-use of the anemia drug. Criticism of the policies, in which Amgen paid rebates to doctors for the purchase of Aranesp, had grown along with questions about the drug's safety.

Aranesp is an erythropoiesis-stimulating agent (ESA). Two other ESA's, Epogen and Procrit, are also currently available. All are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells.

In March 2007, the Food & Drug Administration (FDA) added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. This past November, that black box warning was modified to include more specific dosing information.

Then in March 2008, Amgen and Johnson & Johnson announced that they would be including another black box warning on the drug’s labels. The latest black box warned of the medications’ association with increased tumor growth and shortened survival time in some cancer patients.

Amgen has long offered rebates and discount to oncology clinics for their use of Aranesp. Oncology practices typically buy the drugs they use and then are reimbursed for them by patients and insurers. If doctors pay less for the drugs because of discounts and rebates, they can make a higher profit.

Critics say that such marketing programs encourage doctors to overuse ESAs. The criticism has gotten the attention of Congress, where a probe of the practice is ongoing. In April, Reps. John Dingell and Bart Stupak, both Michigan Democrats, sent letters to Amgen and Johnson & Johnson on Monday, suggesting their marketing campaigns for Procrit, Aranesp and Epogen convinced physicians to prescribe the drugs at unsafe dosages. Senator Charles E. Grassley, Republican of Iowa, said in April that Amgen had provided nearly $800 million in rebates to more than 6,000 facilities in 2006.

Amgen once offered discounts and rebates to doctors based on how much Aranesp they bought. But that program was changed in February, and the company started to offer the discounts and rebates based on the share of a clinic’s anemia drug purchases were represented by Aranesp as opposed to Procrit. At the time, the company maintained that the marketing program was to help Aranesp compete with Procrit, not increase its overall use.

But now, the company has decided to end the rebate program all together. It also said it would stop offering discounts on two other drugs, Neulasta and Neupogen, based on a doctor’s purchase of Aranesp.

But the discount aren't being halted completely. In place of the rebate program, Amgen will now offer bigger discounts at the time of purchase to doctors who buy at least 50 percent of their anemia drugs from Amgen rather than Johnson & Johnson.

More than 44,000 Vials of Procrit Recalled

Wed, 06 Aug 2008 00:00:00 -0700

Procrit is being recalled by Johnson & Johnson subsidiary Ortho Biotech. According to the company's recall notice, the action is necessary because cracks in the necks of a small number of Procrit vials were discovered upon post-manufacturing inspection.

The Procrit recall involves approximately 44,292 vials of lot P114942A distributed between April 15, 2008 and July 17, 2008. The recalled Procrit vials were available in the following packaging configurations:

Individual multi-dose vials 10,000 U/2mL; NDC #59676-312-00; Expiration date 12/10
Cartons containing 4 multi-dose vials 10,000 U/2mL; NDC 59676-312-04; Expiration date 12/10

According to the recall notice, Procrit vials exhibiting even slight cracks may not maintain their sterile condition and should not be used for subcutaneous or intravenous injection. Procrit vials from the recalled lot should be promptly returned by contacting the returned goods service provider, at (800) 668-4391.

Procrit is an erythropoiesis-stimulating agent (ESA). ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. When Procrit was first approved in 1989, the drug was touted as a treatment to lessen fatigue and improve quality of life among cancer and HIV patients with anemia. But since then, Procrit has been forced to undergo several label changes, and the label now states that there was no evidence to back that claim.

Other ESAs include Aranesp and Epogen. All are made by Amgen, but Procrit is sold by Ortho Biotech under a licensing agreement.

Earlier this month, the Food & Drug Administration (FDA) mandated that the labeling of Procrit and other ESAs be modified to say that the drugs shouldn’t be used in cancer patients receiving chemotherapy when a cure of their cancer is anticipated. The FDA also ordered inclusion of a statement that the drugs aren’t to be administered when hemoglobin levels are greater than or equal to 10 grams per deciliter. Language is being removed that seemed to imply that it was safe to continue treating patients until their hemoglobin rose to 12 grams per deciliter.

The FDA ordered the labeling changes because several studies have shown that Procrit and other ESAs increased tumor growth and shortened survival time in some cancer patients.

FDA Forces New Labeling for Procrit, Aranesp and Epogen

Thu, 31 Jul 2008 00:00:00 -0700

Federal regulators have decided that the anemia drugs Aranesp, Epogen and Procrit need to have additional safety-related changes to their labels. The changes mandated by the Food & Drug Administration (FDA) would restrict the use of the drugs in some cancer patients.

Procrit, Aranesp and Epogen are known as erythropoiesis-stimulating agent (ESA). All are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. When Procrit was first approved in 1989, the drug was touted as a treatment to lessen fatigue and improve quality of life among cancer and HIV patients with anemia. But since then Procrit has been forced to undergo five label changes, and the label now states that there was no evidence to back that claim.

This past March, Amgen and Johnson & Johnson announced that they would be including another black box warning on the drug’s labels. The black box warned of the medications’ association with increased tumor growth and shortened survival time in some cancer patients. The warning came on the heels of the PREPARE breast cancer study. That breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. PREPARE showed patients had a higher risk of death on Aranesp. The warning also noted danger for patients with cervical cancer, based on results in December from a study called GOG-191.

That same month, an FDA advisory panel recommended new limits be placed on the drugs. Yesterday's announcement that the agency was requiring further label changes and restrictions is the first time FDA using authority granted to it in 2007 to force a drug maker to change a drug's label. Apparently, the FDA and Amgen were not able to reach agreement over the label changes. According to The New York Times, Amgen had wanted the label to give doctors discretion to initiate therapy before hemoglobin levels dropped to 10 in patients who could not tolerate that degree of anemia. And it wanted mention of the 12 gram upper limit for stopping therapy.

The new label will say that say that the drugs shouldn't be used in cancer patients receiving chemotherapy when a cure of their cancer is anticipated. The FDA also ordered inclusion of a statement that the drugs aren't to be administered when hemoglobin levels are greater than or equal to 10 grams per deciliter. Language is being removed that seemed to imply that it was safe to continue treating patients until their hemoglobin rose to 12 grams per deciliter.

Despite the FDA's tough stance regarding the anemia drug's, the new labeling does not incorporate all of the recommendations the advisory panel made in March. The panel had also advised that patients with advanced breast cancer and head-and-neck cancer shouldn't get the medicines.

Study Says Genetic Tests May Predict if Procrit, Aranesp or Epogen Will Speed Tumor Growth

Tue, 03 Jun 2008 00:00:00 -0700

Some cancer patients treated with the anemia drugs Procrit, Aranesp and Epogen could experience increased tumor growth. However, researcher recently reported that there may be a way to predict which cancer patients are at risk for this devastating side effect.

Procrit, Aranesp and Epogen are known as an erythropoiesis-stimulating agent (ESA). All are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. Over the past 18 months, eight late-stage clinical trials have shown that treatment with ESAs can have an adverse impact on cancer survival.

In March, Amgen and Johnson & Johnson announced that they would be including a black box warning on the drug’s labels about their association with increased tumor growth and shortened survival time in some cancer patients. The latest black box to be included on the labeling of Procrit, Aranesp and Epogen came on the heels of the PREPARE breast cancer study. That breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. The new black box will cite information from PREPARE which showed patients had a higher risk of death on Aranesp. It also notes danger for patients with cervical cancer, based on results in December from a study called GOG-191.

A week later, an FDA advisory panel voted 13 to 1 in favor of allowing the continued sale of the ESAs for use in cancer patients undergoing chemotherapy. However, the panel voted 11 to 2 in recommending that the drugs not be used in cancer patients who are likely to be cured from their treatments, which suggests the drugs should only be used as part of a best-supportive care regimen for patients with advanced cancer or those expected to die from the cancer. The panel also voted 9 to 5 that the shouldn’t be used in patients with breast cancer as well as patients with head and neck cancer.

Sales of the anemia drugs have slumped amid the safety concerns. But on Sunday, researchers from the University of Washington presented a study at the American Society of Clinical Oncology in Chicago that indicated a genetic test may help predict whether giving cancer patients anemia drugs could make their cancer worse. In the study, the research group measured levels of erythropoietin receptor messenger RNA in tumor samples from 101 patients with head and neck cancer who took part in a trial of Aranesp. The aim was to test whether the drug might be acting on tumor blood vessels and other membranes as well as red blood cells.

Among patients treated with radiation therapy alone, without prior surgery, tumors with high-levels of this type of RNA messenger progressed faster in patients who received the anemia drug compared with patients given a placebo. Testing for the RNA messenger gene could allow the anemia drugs to be used in a target way, the researchers said.

However, the researchers emphasized that the findings were preliminary and need to be confirmed with a larger analysis of tumor specimens.

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.

Congress Investigates Procrit, Epogen and Aranesp Marketing

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

Two members of Congress are looking into to allegations that the marketing of Procrit, Aranesp and Epogen encouraged overuse of the anemia drugs, placing some patients in danger. Reps. John Dingell and Bart Stupak, both Michigan Democrats, sent letters to Amgen and Johnson & Johnson on Monday, suggesting their marketing campaigns for Procrit, Aranesp and Epogen convinced physicians to prescribe the drugs at unsafe dosages.

Procrit, Aranesp and Epogen are known as an erythropoiesis-stimulating agent (ESA). All are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. Procrit, Aranesp and Epogen have been touted as treatments to lessen fatigue and improve quality of life among cancer and HIV patients with anemia. But since then the drugs has been forced to undergo five label changes, and the labels now state that there was no evidence to back that claim. Rather, the drugs are only approved to raise red blood cell counts high enough to avoid transfusions.

Last March, the Food & Drug Administration (FDA) added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. This past November, that black box warning was modified to include more specific dosing information.

Last month, Amgen and Johnson & Johnson announced that they would be including another black box warning on the drug’s labels. The latest black box warned of the medications’ association with increased tumor growth and shortened survival time in some cancer patients. A week after those warnings were added, the FDA cancer-drugs advisory committee voted 13 to 1 in favor of allowing the continued sale of the ESAs for use in cancer patients undergoing chemotherapy. However, the panel voted 11 to 2 in recommending that the drugs not be used in cancer patients who are likely to be cured from their treatments. The panel also voted 9 to 5 that the shouldn’t be used in patients with breast cancer as well as patients with head and neck cancer. The FDA is not bound by the recommendations of its advisory panels, however, it usually does follow them.

Reps. Dingell and Stupak want Johnson & Johnson to turn over information regarding its promotion of Procrit. Some of the company's television advertisements suggested Procrit improved quality of life by showing patients who appeared healthy and active. The Congressmen said such promotions encouraged "excessive and dangerous off-label use of the drug." Prior to last year's warnings on dosage, many doctors would prescribe unapproved high doses of the drugs. Johnson & Johnson stopped direct-to-consumer Procrit ads in 2005.

For its part, Amgen never engaged in direct-to-consumer marketing of Aranesp or Epogen. However, the Congressmen's letter questioned whether the company's practice of granting higher rebates to doctors who ordered more vials of Amgen drugs might have led to overuse.

Procrit, Aranesp, Epogen Should Be Allowed for Cancer Patients, With Some Restrictions, FDA Panel Says

Thu, 13 Mar 2008 00:00:00 -0700

An advisory panel has weighed in on the safety issues surrounding Procrit, Aranesp and Epogen, anemia drugs used to treat chemotherapy patients and others. While the Food and Drug Administration (FDA) advisory panel did not call on the agency to rescind the approval of Procrit, Aranesp and Epogen to treat cancer patients, it did recommend more limited restrictions on the drugs.

Procrit, Aranesp and Epogen are known as an erythropoiesis-stimulating agent (ESA). All are made by Amgen, but Procrit is sold by Johnson & Johnson subsidiary Ortho Biotech under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. When Procrit was first approved in 1989, the drug was touted as a treatment to lessen fatigue and improve quality of life among cancer and HIV patients with anemia. But since then Procrit has been forced to undergo five label changes, and the label now states that there was no evidence to back that claim.

Last Friday, Amgen and Johnson & Johnson announced that they would be including another black box warning on the drug's labels. The latest black box warned of the medications' association with increased tumor growth and shortened survival time in some cancer patients. The latest black box to be included on the labeling of Procrit, Aranesp and Epogen came on the heels of the PREPARE breast cancer study. That breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. The new black box will cite information from PREPARE which showed patients had a higher risk of death on Aranesp. It also notes danger for patients with cervical cancer, based on results in December from a study called GOG-191.

Last March, the FDA also added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. This past November, that black box warning was modified to include more specific dosing information.

Today, the FDA convened a meeting of its cancer-drugs advisory committee to recommend what additional action the regulator should take in regards to Procrit, Aranesp and Epogen. The panel ultimately voted 13 to 1 in favor of allowing the continued sale of the ESAs for use in cancer patients undergoing chemotherapy. However, the panel voted 11 to 2 in recommending that the drugs not be used in cancer patients who are likely to be cured from their treatments, which suggests the drugs should only be used as part of a best-supportive care regimen for patients with advanced cancer or those expected to die from the cancer. The panel also voted 9 to 5 that the shouldn't be used in patients with breast cancer as well as patients with head and neck cancer. The FDA is not bound by the recommendations of its advisory panels, however, it usually does follow them.

Procrit, Aranesp, Epogen Could be Restricted by FDA

Wed, 12 Mar 2008 00:00:00 -0700

Procrit, Aranesp and Epogen, anemia drugs used to treat chemotherapy patients, could soon have new restrictions imposed on them by the Food and Drug Administration (FDA). Late last week, the FDA announced a new black box warning for Procrit, Aranesp and Epogen regarding their association with shortened survival and increased tumor growth in some cancer patients. Now there is speculation that the FDA is getting ready to rescind it approval of Procrit, Aranesp and Procrit to treat anemia in cancer patients.

Aranesp, Epogen and Procrit are known as erythropoiesis-stimulating agents (ESAs). All are made by Amgen, but Procrit is sold by Johnson & Johnson under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. Approved uses of ESAs are for the treatment of anemia in patients with chronic kidney failure; for cancer patients whose anemia is caused by chemotherapy; and for those infected with the human immunodeficiency virus (HIV) whose anemia is caused by the HIV drug AZT (zidovudine). ESAs are also approved to reduce the number of transfusions during and after major surgery.

The latest black box to be included on the labeling of Procrit, Aranesp and Epogen came on the heels of the PREPARE breast cancer study. That breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. The new black box will cite information from PREPARE which showed patients had a higher risk of death on Aranesp. It also notes danger for patients with cervical cancer, based on results in December from a study called GOG-191.

That warning followed the addition of two other black box warnings for the drugs. The FDA ordered a black box warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. Last March, the FDA also added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. This past November, that black box warning was modified to include more specific dosing information.

Tomorrow, the FDA's cancer-drugs advisory committee will recommend what action the regulator should take. According to The Wall Street Journal, the FDA will ask the advisory panel to consider several restrictions on Procrit, Aranesp and Epogen beyond the black box warnings. According to documents made public by the FDA yesterday, this could include eliminating their approval for cancer patients. If that happened, the drugs would remain on the market for other uses, particularly in kidney failure. And doctors could still choose to prescribe Procrit, Aranesp and Epogen for cancer patients as an off-label use, as physicians are free to use approved drugs in any way they see fit.

Other restrictions the FDA could impose on Procrit, Aranesp and Epogen include requiring cancer patients to sign informed consents before they take the medicines, confining distribution of the drugs, or asking the drugs' makers to voluntarily limit their advertising and promotion. The FDA is also asking advisors to weigh targeted limits, such as recommending the drugs' use only in small-cell-lung-cancer patients.

Aranesp, Epogen, Procrit Get Another Black Box Warning

Mon, 10 Mar 2008 00:00:00 -0700

Aranesp, Epogen and Procrit, drugs used to treat anemia in patients undergoing chemotherapy, will soon bear new black box warnings that they may shorten survival time in patients with certain types of tumors. Amgen's Aranesp and Epogen, and Johnson & Johnson's Procrit, have been under scrutiny for some time after several studies showed some patients treated with the drugs die sooner than others. In addition to the warning on survival time, the new black box warning for Aranesp, Epogen and Procrit will also say that tumors may spread more quickly in patients on the drugs.

Aranesp, Epogen and Procrit are known as erythropoiesis-stimulating agents (ESAs). All are made by Amgen, but Procrit is sold by Johnson & Johnson under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. Approved uses of ESAs are for the treatment of anemia in patients with chronic kidney failure; for cancer patients whose anemia is caused by chemotherapy; and for those infected with the human immunodeficiency virus (HIV) whose anemia is caused by the HIV drug AZT (zidovudine). ESAs are also approved to reduce the number of transfusions during and after major surgery.

A year ago, the Food & Drug Administration (FDA) ordered a “black box” warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. Last March, the FDA added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. This past November, that black box warning was modified to include more specific dosing information.

The new black box warnings on Aranesp, Epogen and Procrit come on the heels of the PREPARE breast cancer study. That breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. The new black box will cite information from PREPARE which showed patients had a higher risk of death on Aranesp. It also notes danger for patients with cervical cancer, based on results in December from a study called GOG-191.

The new warning for the anemia drugs is being added to precautions outlined in a black box at the top of prescribing information for the medicines. Amgen and Johnson & Johnson are also sending a letter to doctors informing them of the added warning.

The FDA has scheduled an advisory panel meeting for March to further discuss the safety issues surrounding Aranesp, Epogen and Procrit. At that meeting, the FDA could place more restrictions on the drugs, including a recommendation to lower the dose or that doctors stop prescribing the drugs for certain cancers.

Epogen, Aranesp and Procrit Linked to Potentially Fatal Blood Clots

Wed, 27 Feb 2008 00:00:00 -0800

Epogen, Aranesp and Procrit, anemia drugs used to treat cancer patients, have been linked to a higher risk of a potentially fatal type of blood clot. According to a review published in the February 27 issue of the Journal of the American Medical Association, anemia drugs—medications designed to fight fatigue and other symptoms associated with cancer treatment-related anemia—significantly increase the risk of death and serious side effects in cancer patients. The risk of death is increased by 10 percent when taking ESAs — erythropoiesis-stimulating agents—and the risk of blood clots—venous thromboembolisms (VTE)—increased by 57 percent. "What we've done here is put together the totality of the evidence and found two things that are concerning: The increased risk of VTE and the increased risk of mortality," said the review's lead author, Dr. Charles Bennett, the A.C. Beuhler professor of geriatric medicine at Northwestern University's Feinberg School of Medicine.

The U.S. National Institutes of Health explains that ESAs—erythropoietin (Epogen, Procrit) and darbepoetin (Aranesp)—work by stimulating bone marrow to produce new red blood cells. Epogen, Aranesp and Procrit are used in the treatment of chemotherapy-related anemia and to treat anemia in people with chronic kidney disease who are also on dialysis.

Health experts have raised concerns about Epogen, Aranesp and Procrit before. In kidney patients, past research showed that if ESAs are used to raise hemoglobin levels above 12 grams per deciliter of blood, the risk of death increases. Also, past cancer research revealed that ESAs may be associated with more rapid tumor growth in addition to an increased risk of death. Because of this, the U.S. Food and Drug Administration (FDA) last year had the drugs' manufacturers add a "black box" warning to the medications. The black box—the strongest drug warning—indicates that the medications should be used at the lowest possible doses to avoid risks such as blood clots, heart attacks, stroke, congestive heart failure, increased tumor growth, and an increased risk of death. The FDA also recommended that ESAs be prescribed at the lowest possible doses since trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.

But there are critics to these findings. "If you use ESAs the way they're supposed to be used, I really don't see clinically what they're talking about in the trials," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, Louisiana. "Many of the trials that changed the FDA prescribing guidelines were done in Europe and outside the guidelines of the US. I still think ESAs are extraordinarily useful and safe medications when used in an efficacious manner. I would be treated with these agents if I had cancer," Brooks said.

The study included 51 phase 3 clinical trials completed in the 20-year period between 1985 and 2005. Survival was evaluated in 13,613 cancer patients; the risk of VTE was evaluated in 8,172 people with cancer. The type of cancer varied widely from study to study. "At the end of the day, these data are very provocative and it's important for people [that] make clinical guidelines to review the data," said Bennett, who's also a hematologist/oncologist at Northwestern Memorial Hospital and the Jesse Brown VA Medical Center in Chicago. "Patients should be informed of the risks and benefits of these drugs," he added.

Aranesp, Epogen and Procrit Policy Justified, Medicare Official Says.

Mon, 11 Feb 2008 00:00:00 -0800

More trouble for Aranesp, Epogen and Procrit. Senior Medicare official Dr. Barry Straube said evidence—including two studies—is mounting in the case for cutting the use of controversial anemia drugs sold by Amgen Inc. and Johnson & Johnson. Medicare cut payments for the use of those drugs in cancer patients last year and the U.S. Centers for Medicare and Medicaid Services (CMS) is reviewing its decision following criticism from cancer doctors and drug makers.

Studies continue to question the drugs' safety and back the policy Straube, chief medical officer at CMS, enacted. "I think that our national coverage decision has been shown, with even more evidence coming out since we made it, to have been the right thing to do," Straube said. The drugs are erythropoietin-stimulating agents, also known as ESAs, and include Amgen's Aranesp and Johnson & Johnson's Procrit. Both medications are multi-billion-dollar selling drugs. CMS issued payment restrictions in 2007 after four large studies raised safety concerns and the Food and Drug Administration (FDA) required a stronger warning on the drugs' labels. The drugs can boost risk of heart problems and even death, especially at high doses.

Labels for Aranesp, Epogen, and Procit were updated to include revised dosage guidelines and information on the drugs’ cardiovascular side effects. The modifications followed the FDA ordering of a black box warning—the strongest drug labeling—about cardiovascular problems and other safety issues. Amgen manufactures all three medications although Johnson & Johnson sells Procrit under a licensing agreement. The drugs are part of a class of drugs known as ESAs that treat anemia in patients with kidney disease or certain cancers by boosting red blood cells. Several studies linked the drugs to cardiovascular problems and deaths and have been tied to worsening tumors when used in cancer patients. Soon after Epogen was introduced, some doctors attempted to use it to increase patients’ hemoglobin—the part of the blood cell that carries oxygen—to levels as high as those in healthy patients (14). Two clinical trials showed the large dosage required to reach these levels could lead to heart problems and death and the black box warning cautioned doctors that the medications should be administered at the lowest dose possible to bring blood counts to the lowest level needed to avoid transfusions. The modified black box warning has more specific dosing information stating dosing should be individualized. For kidney patients, the revised warning reads that patients experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher versus lower hemoglobin levels in two clinical studies’ rather than the more generic warning that risks were seen when hemoglobin levels of greater than 12 were targeted. Following the revised warning, Medicare announced it would not pay for Aranesp, Epogen, and Procrit in patients whose hemoglobin levels were at 10 grams per deciliter.

Straube said he believes the FDA will consider restricting use of the drug in some cancer patients. The entire drug class has been under review as debates continue over whether anemia drugs increase the risk of heart attack and stroke and fuel the growth of cancer.

Procrit, Aranesp and Epogen to See More FDA Scrutiny After Two Studies Show Increased Tumor Growth in Some Cancer Patients Treated with ESAs

Thu, 03 Jan 2008 00:00:00 -0800

Two new studies suggest that Procrit, Aranesp and Epogen could carry more risks than first thought, prompting the Food & Drug Administration (FDA) to consider subjecting the anti-anemia drugs to even more regulatory action. The FDA already strengthened warnings on Procrit, Aranesp and Epogen twice last year and will hold another advisory panel meeting in the next few months to discuss the new studies. The two new studies were not included in the most recent label update of the drugs on Nov. 8, the FDA said.

Aranesp, Epogen and Procrit are known as erythropoiesis-stimulating agents (ESAs). All are made by Amgen, but Procrit is sold by Johnson & Johnson under a licensing agreement. ESAs are a bioengineered version of a natural protein made in the kidney that stimulates the bone marrow to produce more red blood cells. FDA-approved uses of ESAs are for the treatment of anemia in patients with chronic kidney failure; for cancer patients whose anemia is caused by chemotherapy; and for those infected with the human immunodeficiency virus (HIV) whose anemia is caused by the HIV drug AZT (zidovudine). ESAs are also approved to reduce the number of transfusions during and after major surgery.

Recently, several studies have linked the anemia drugs to cardiovascular problems and deaths. They have also been tied to worsening tumors when used in cancer patients. A year ago, FDA ordered a “black box” warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. In March, the FDA added another black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. Last month, that black box warning was modified to include more specific dosing information.

The latest ESA studies showed that patients with breast or advanced cervical cancers who received ESAs to treat anemia caused by chemotherapy died sooner or had more rapid tumor growth than similar patients who didn't receive the anemia drug. The agency said the two new studies, along with six that are included in the current drug labels "show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid or cervical cancers received ESAs compared to patients who did not receive this treatment.” The FDA said ESAs were administered in an attempt to achieve a hemoglobin level of 12 grams per deciliter or greater in the studies, which is higher than current dosing recommendations.

Aranesp, Epogen and Procrit Linked to Leukemia in Some Patients

Tue, 11 Dec 2007 00:00:00 -0800

Aranesp, Epogen and Procrit have been linked to yet another deadly side effect. New research suggests that the anemia drugs, known as erythropoiesis-stimulating agents (ESAs), might play a role in the development of a form of leukemia when they are used to treat people with a rare blood disorder known as myelofibrosis. This is just the latest bit of bad news related to Aranesp, Epogen and Procrit this year, which have been the subject of an ongoing Food & Drug Administration (FDA) safety review. Just last month, the FDA strengthened safety warnings on the drugs amid concerns that they increase the risk of death, heart attack, stroke and the progression of other cancers.

Myelofibrosis is a bone marrow disorder that interrupts the body's normal production of blood cells, leading to severe anemia and enlargement of the spleen. While myleofibrosis can progress to leukemia on its own, researchers at the Mayo Clinic found that patients treated with ESAs were far more likely to develop the blood cancer. They examined the records of 311 patients with primary myelofibrosis from 1976 to 2006 to see what factors led some of them to advance to acute leukemia. They found that patients in the study who took ESAs tended to be sicker, and were more likely to develop leukemia.

ESAs like Aranesp, Epogen and Procrit treat anemia in patients with kidney disease or certain cancers by boosting red blood cells. However, several studies have linked the anemia drugs to cardiovascular problems and deaths. They have also been tied to worsening tumors when used in cancer patients. A year ago, the FDA ordered that a “black box” warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. In March, the FDA added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. Last month, that black box warning was modified to include stronger language and more specific dosing information.

Last week, Amgen, the manufacturer of all three drugs, said a study done on breast cancer patients treated with the Aranesp showed that it offered them little help, and also placed them at a higher risk of death. Amgen said it was considering further warnings for the drugs. Aranesp and Epogen are marketed by Amgen, while Procrit is sold by Johnson & Johnson under a licensing agreement with Amgen.

Following the release of the Aranesp breast cancer study, the FDA announced that it would be holding yet another advisory panel meeting in March to discuss the safety of Aranesp, Epogen and Procrit. The March meeting will be the fourth time the FDA has held such a meeting to discuss ESAs. Following one of these meetings in May, the Centers for Medicare and Medicaid Services changed the reimbursement policy for Aranesp and other ESAs. Now doctors will only be paid for using a low dose of the drug.

Since safety concerns over Aranesp, Epogen and Procrit first surfaces, Amgen has lost nearly $19 billion in market value.

Amgen Warns of More Aranesp Lable Changes

Mon, 10 Dec 2007 00:00:00 -0800

Aranesp, an anemia drug often used to treat chemotherapy patients, could soon have safety information on its label updated yet again, the drug’s maker announced last week. Amgen Inc. announced that it was considering label changes for Aranesp after the results of a study done on breast cancer patients treated with the drug showed that it offered them little help, and also placed them at a higher risk of death.

The Aranesp breast cancer study was one of 5 clinical trials that Amgen had agreed to after the safety of Aranesp was called into question. Aranesp, and two other drugs made by Amgen, Epogen and Procrit, are all part of a class of drugs known as erythropoiesis-stimulating agents (ESAs). Procrit is marketed by Johnson & Johnson under a licensing agreement with Amgen.

ESAs treat anemia in patients with kidney disease or certain cancers by boosting red blood cells. However, several studies have linked the anemia drugs to cardiovascular problems and deaths. They have also been tied to worsening tumors when used in cancer patients. A year ago, the Food & Drug Administration (FDA) ordered a “black box” warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. In March, the FDA added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. Last month, that black box warning was modified to include more specific dosing information.

Following the release of the Aranesp breast cancer study, the FDA announced that it would be holding yet another advisory panel meeting in March to discuss the safety of Aranesp, Apogent and Procrit. The March meeting will be the fourth time the FDA has held such a meeting to discuss ESAs. Following one of these meetings in May, the Centers for Medicare and Medicaid Services changed the reimbursement policy for Aranesp and other ESAs. Now doctors will only be paid for using a low dose of the drug.

None of this is good news for Amgen, as Aranesp is its biggest selling product. Amgen, based in Thousand Oaks, Calif., has lost about $19 billion in market value this year after studies showed its anemia drugs raised the risk of heart attack, stroke and death at high doses. Last week, after it announced that it was considering more label changes, Amgen stock dropped more than 5 percent. The worst possible outcome for Amgen would be if the latest breast cancer data convinced the FDA panel to vote to recommend against using ESAs to treat other cancers where there's been negative data as well, such as neck and head cancer.

Aranesp Study Shows Little Benefit for Breast Cancer Patients, Possibly Higher Rates of Death, Tumor Growth

Mon, 03 Dec 2007 00:00:00 -0800

Aranesp, an anemia drug, does not appear to benefit breast cancer patients. Amgen Inc., maker of Aranesp, recently said interim results from an independent study involving breast cancer patients found Aranesp did not enhance the effect of chemotherapy prior to surgery. The study involved over 700 patients and evaluated whether Aranesp prevented anemia and augmented the therapeutic effects of chemotherapy regimens.

Amgen also reported that participants who received Aranesp had numerically more deaths and reports of tumor growth than control group patients. Amgen cautioned that the results-revealed amid concerns about the overuse and safety of the anemia drug class-were preliminary and conclusions should not be made until completion of the final study report. A formal statistical analysis of survival is anticipated in early 2009. The interim analysis shows the use of Aranesp to support neo-adjuvant chemotherapy has no significant impact on tumor response to chemotherapy at the time of surgery. There were no deaths during the treatment period, researchers said; however, preliminary long-term, follow-up data revealed more deaths in the group receiving Aranesp, with more tumor progression events versus the control group.

The entire drug class, called erythropoiesis-stimulating agents (ESAs), has been under a microscope as debates rage over whether anemia drugs increase the risk of heart attack and stroke, and whether they may play a role in fueling the growth of cancer.

Labels for Aranesp, Epogen, and Procit had been updated to include revised dosage guidelines and information on the drugs' cardiovascular side effects. The modifications followed the Food and Drug Administration's (FDA) ordering of a black box warning-the strongest drug labeling-about cardiovascular problems and other safety. Amgen manufactures all three medications although Johnson & Johnson sells Procrit under a licensing agreement. The drugs are part of a class of drugs known as erythropoiesis-stimulating agents (ESAs) that treat anemia in patients with kidney disease or certain cancers by boosting red blood cells. Several studies linked the drugs to cardiovascular problems and deaths and have been tied to worsening tumors when used in cancer patients. Soon after Epogen was introduced, some doctors attempted to use it to increase patients' hemoglobin-the part of the blood cell that carries oxygen-to levels as high as those in healthy patients (14). Two clinical trials showed the large dosage required to reach these levels could lead to heart problems and death and the black box warning cautioned doctors that the medications should be administered at the lowest dose possible to bring blood counts to the lowest level needed to avoid transfusions. The modified black box warning now has more specific dosing information and states dosing should be individualized. For kidney patients, the revised warning read that patients experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher versus lower hemoglobin levels in two clinical studies' rather than the more generic warning that risks were seen when hemoglobin levels of greater than 12 were target. Following the revised black box warning, Medicare announced it would not pay for Aranesp, Epogen and Procrit in patients whose hemoglobin levels were at 10 grams per deciliter.

Aranesp, Epogen, Procrit Label Updated Over Safety Concerns

Thu, 08 Nov 2007 00:00:00 -0800

The labels of Aranesp, Epogen and Procrit, drugs used to treat anemia, are being updated to include new dosage guidelines and specific information on the drugs’ cardiovascular side effects.   The label modifications come less than a year after the Food & Drug Administration (FDA) ordered a “black box” warning regarding cardiovascular problems and other safety issues posed by the drugs be included on their labels. All three medications are manufactured by Amgen, although Procrit is sold by Johnson & Johnson under a licensing agreement.

Aranesp, Epogen and Procrit are all part of a class of drugs known as erythropoiesis-stimulating agents (ESAs). ESAs treat anemia in patients with kidney disease or certain cancers by boosting red blood cells. However, several studies have linked the anemia drugs to cardiovascular problems and deaths. They have also been tied to worsening tumors when used in cancer patients. Soon after Epogen was introduced, some doctors attempted to use it to increase patients’ hemoglobin (the part of the blood cell that carries oxygen) to levels as high as14 grams.   A healthy person would normally have a hemoglobin level between 13.5 and 14. Two clinical trials showed that the large dosage required to attain such high hemoglobin levels could lead to heart problems and death. In March, the FDA added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. The warning labels said hemoglobin levels should not be allowed to go above 12 grams per deciliter of blood.

The modified black box warning on Aranesp, Epogen and Procrit now has more specific dosing information. It now states that dosing should be individualized to "achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL."   For kidney patients, the new warning now reads that “patients experienced greater risks for death and serious cardiovascular events when administered ESAs to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies' rather than the more generic warning that risks were seen when hemoglobin levels of greater than 12 were target.

Amgen also announced that it planned to ask the Centers for Medicare and Medicaid Services to loosen payment restrictions for Aranesp, Epogen and Procrit. Shortly after the FDA added the black box warning in March, Medicare announced that program would not pay for Aranesp, Epogen and Procrit in patients whose hemoglobin levels were at 10 grams per deciliter.

Proposed Aranesp, Epogen, Procrit Dosage Limit Rejected by FDA Advisory Panel

Wed, 12 Sep 2007 00:00:00 -0700

An advisory panel has concluded that Amgen's anemia medications should not be subject to a new dosage limit proposed by the Food & Drug Administration (FDA). Yesterday, the panel voted 15-4 against a new limit for Aranesp, Epogen and Procrit, which are used to treat anemia in patients experiencing kidney failure. All three are manufactured by Amgen, although Procrit is sold by Johnson & Johnson under a licensing agreement.

Several studies have linked the anemia drugs to cardiovascular problems and deaths. They have also been tied to worsening tumors when used in cancer patients. The drugs improve anemia by increasing red blood cells, something that had previously been accomplished with blood transfusions. But soon after Epogen was introduced, some doctors attempted to use it to increase patients’ hemoglobin (the part of the blood cell that carries oxygen) to levels as high as 14 grams. A healthy person would normally have a hemoglobin level between 13.5 and 14. Two clinical trials showed that the large dosage required to attain such high hemoglobin levels could lead to heart problems and death. In March, the FDA added a black box warning to the drugs’ labels cautioning doctors that the medications should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. The warning labels said hemoglobin levels should not be allowed to go above 12 grams per deciliter of blood.

Shortly after the FDA added the black box warning, Medicare announced that program would not pay for Aranesp, Epogen and Procrit in patients whose hemoglobin levels were at 10 grams per deciliter. That decision sparked controversy among doctors and members of Congress. As a result, Medicare had been waiting for the outcome of yesterday’s advisory panel meeting before enforcing its new dosing regulations.

Prior to the meeting, the FDA had proposed setting a target hemoglobin level of 11 for the medications. The panel heard from representatives from Amgen, as well as patient representatives and kidney specialists. They expressed fears that the proposed limit would leave many patients under-treated, and at risk for blood transfusions. Many panelists who voted against the proposed level of 11 said that more flexibility in dosing was needed, although most agreed that some guidelines were necessary. Several backed Amgen’s proposed hemoglobin range of 10- to-12 grams. While higher than the FDA proposed limit, that range is still lower than the 11-to-13 range found in some kidney treatment guidelines. At least one panel member expressed concern that 18 years after Epogen received its approval, dosage was still as subject of controversy. He criticized Amgen for not conducting more clinical trails.

Despite the vote in Amgen’s favor, Aranesp, Epogen and Procrit could still face additional changes to their labels. The FDA says that claims made on the labels that the drugs improve patient’s quality of life did not stand up to clinical scrutiny. The FDA is considering removing those statements from the products’ labels; however the advisory panel was not asked to vote on that issue.

Proposed Aranesp, Epogen, Procrit Dosage Limit Rejected by FDA Advisory Panel

Wed, 12 Sep 2007 00:00:00 -0700

Controversy over Aranesp, Epogen and Procrit to Be Addressed by FDA Panel

Mon, 10 Sep 2007 00:00:00 -0700

Aranesp, Epogen and Procrit, drugs given to anemia patients suffering end-stage kidney failure, will be taken up by a Food & Drug Administration (FDA) advisory panel tomorrow.   Earlier this year, the FDA added a black box warning to the products’ labels recommending that the drugs be used at the lowest dose possible. But what constitutes the minimum dose for these medications has been a subject of controversy.

Aranesp, Epogen and Procrit are all erythropoiesis-stimulating agents (ESAs) given to anemia patients suffering kidney failure and undergoing chemotherapy treatment.   Prior to the development of these drugs, such anemia was treated with blood transfusions. In March, a black box warning was added to the drugs’ labels after the FDA discovered that doctors were using the medications to increase red blood cell counts to unsafe levels.   The new warning labels advised that the ESAs should be administered at the lowest dose possible in order to bring red blood cell counts to the lowest level necessary to avoid transfusions. The warning labels said hemoglobin (red blood cell) levels should not be allowed to go above 12 grams per deciliter of blood.   But the label recommendation did not specify what the lowest hemoglobin should be.   Now, no one can agree on what the lowest possible hemoglobin level is, and the FDA is looking to the advisory panel for answers.

The FDA has not pinpointed a proper dosing for ESAs, but has said that there is evidence that a minimum hemoglobin level of 11 could benefit patients. However, an FDA review of the drugs’ safety found that more research focusing on proper dosing is needed. Amgen, the maker of Aranesp and Epogen, claims that a target hemoglobin range should be 11 to 12 grams per deciliter for kidney patients, and that hemoglobin in kidney failure patients should not be allowed to fall below 10.

The dispute over proper ESA dosing came to head a month after the black box warning was added.   Because the treatment of kidney patients is a major expense for Medicare, the addition of the warning prompted the program to decide that it would not pay for Aranesp, Epogen and Procrit in patients whose hemoglobin levels were at 10 grams per deciliter. That decision sparked controversy among doctors and members of Congress. As a result, Medicare has been waiting for the outcome of tomorrow’s FDA advisory panel meeting before enforcing its new dosing regulations.

Muddying the waters even more, the FDA says that studies indicating that ESAs significantly improved a patient’s quality of life did not “supply sufficient evidence of efficacy to retain these claims” on the drug labels. The FDA also said that those studies may not meet current regulatory guidelines. But Amgen insists that the data involving quality of life is conclusive.

FDA Panel Highlights Safety Concerns of Anemia Drugs in Cancer Patients

Fri, 11 May 2007 00:00:00 -0700

In a high-profile meeting this week, an expert panel of the U.S. Food and Drug Administration (FDA) raised significant concerns about the use of the anemia drug erythropoietin in treating cancer patients. According to the findings of the Oncologic Drugs Advisory Committee, the drug, sold by Amgen as Aranesp and by Johnson & Johnson as Procrit, is severely overused in cancer patients and should have new restrictions and guidelines placed on its administration.

Erythropoietin is in a class of drugs known as erythropoiesis-stimulating agents, or ESAs, which are intended to reduce the need for red blood cell transfusions in patients suffering from anemia. (Transfusions are considered a high-risk treatment.) The drug was initially approved for patients suffering from kidney failure, but its approved usage was expanded in 1993 to include cancer patients who were suffering from chemotherapy-induced anemia.

However, in a briefing document released by the FDA ahead of the meeting, the agency said, "Based on data provided to the FDA, there is no evidence that ESAs improve quality of life or cancer outcomes" in these chemotherapy patients. They also note that "data continue to accumulate regarding the increased risks of mortality and of possible tumor promotion from the use of ESAs." They cite a number of recent studies that have found "increased mortality" in ESA patients with cancer. "Given the data from recent clinical studies," the document notes, "it is appropriate to re-assess the safety of ESAs in patients with cancer and to re-evaluate the net clinical benefit of ESAs in this setting."

"As of March 2007," the FDA says, "there are five randomized clinical trials that demonstrated decreased survival times in cancer patients receiving ESAs compared with those receiving transfusion support. There are three randomized studies that demonstrate poorer tumor outcomes in cancer patients receiving ESAs compared with those receiving transfusion support." The FDA also noted that the risks of blood transfusions have lessened significantly since 1993, when it first approved ESAs for use in chemotherapy patients.

In light of these findings, the advisory committee voted to ban the use of these drugs on patients with certain types of cancer. The committee also recommended placing greater restrictions on its overall usage, including stopping the use of ESAs once chemotherapy treatments are over. The committee unanimously decided that more studies were necessary because most of the previous research was conducted on patients receiving higher than recommended dosages of the drug.

There are about a million cancer patients receiving chemotherapy in the Unites States every year, and nearly half of them receive ESAs to treat chemotherapy-induced anemia. When the drugs were approved for use in anemic cancer patients in 1993, their effects on overall survival rates and on tumor promotion were not tested at all. The only test at the time was to see whether or not the drugs reduced the need for blood transfusions.

Over-prescription of Procrit, Aranesp, and a third drug, Epogen, has become a major health-care problem in the United States. In March, a warning was added to labels to make sure that only the minimum dosage necessary to avoid transfusions would be prescribed. "Recently completed studies describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses," the FDA said in March. "In other studies, more rapid tumor growth occurred in patients with head and neck cancer who received these higher doses.

"In studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopedic surgery."

The labeling change was the fourth time in the past decade that the products' label warnings were forced to be updated. At the time, Dr. Steven Galson, director of FDA's Center for Drug Evaluation and Research, said, "The new studies provide significant new information for both prescribers and patients, and the new information applies to all ESAs, which share the same mechanism of action. The safety of these products will be discussed when the Oncologic Drugs Advisory Committee (ODAC) meets in May and further revisions to the labeling may occur after that meeting." A meeting addressing the risks of ESAs on kidney patients will take place later this year.

ESAs are "genetically engineered forms of the naturally occurring human protein, erythropoietin." Erythropoietin is produced by the kidneys and increases red-blood-cell levels. Currently, the FDA has only approved these drugs for treating anemia in patients with chronic kidney failure and in patients whose anemia is a result of chemotherapy. Combined domestic sales of ESAs reached approximately $10 billion last year alone. Anemia drugs are currently Medicare's largest drug expenditure.

FDA panel wants more anemia drug studies

Thu, 10 May 2007 00:00:00 -0700

Two months after federal regulators ordered additional warnings be added to the labels of blockbuster anemia drugs, government advisers said Thursday Amgen Inc. and Johnson & Johnson should be required to add more warnings and conduct additional safety studies.

The Food and Drug Administration's outside panel of experts voted overwhelmingly in favor of expanding warnings about the risks of death, blood clots and other side effects for Amgen's Aranesp and Johnson & Johnson's Procrit.

Wall Street analysts said prior to the meeting that the biggest threat to the revenue the companies get from these drugs would be if panelists wanted to add warning labels that would limit prescribing the drugs to certain patients.

A drop in anemia drug sales would pose a much larger challenge to biotech maker Amgen than to diversified competitor Johnson & Johnson. Last year Aranesp was Amgen's best-selling product with sales of $4.1 billion, or nearly 30 percent of full-year revenue. When combined with Epogen, a version of the drug used only in kidney failure patients on dialysis, the medication accounts for more than half of Amgen's annual sales.

The panel of experts, at a meeting in a hotel here, also voted unanimously that the companies should be required to conduct new studies to definitively prove the safety of the two widely prescribed drugs. Anemia drugs accounted for $10 billion in revenue for these two companies last year alone.

The FDA is not required to follow the panel's recommendations although it typically does.

Johnson & Johnson and Amgen have conducted more than a dozen studies of the drugs to date although panelists Thursday said what is needed is a large, comprehensive study of whether people who take the drugs die sooner than those who don't.

In March, the FDA ordered warnings be added to the drugs' labels after recent studies showed using the drugs outside of approved guidelines could increase the growth of tumors and the risk of death in some patients.

It was not made clear during Thursday's meeting whether the additional warnings favored by panelists would apply to all uses of the drugs or just non-approved use.

Many physicians prescribe anemia drugs aggressively to raise their patients' red blood cell levels to that of a healthy person, believing the higher red blood cell levels improves quality of life.

In presentations to the panel Thursday, FDA staff focused on four studies suggesting overprescribing or prescribing for unapproved uses could in fact increase a patient's risk of death.

Still, a majority of panelists voted against requesting that product packaging be changed to recommended lower dosing levels.

"We will be working with the FDA as they consider the committee's recommendations," said Amgen spokeswoman Tricia Hawkins.

A spokeswoman for Johnson & Johnson stressed that the company has not seen negative side effects from its drug when used as directed.

"When used according to the label, Procrit is safe and effective, and has an acceptable risk-benefit profile," said J&J's Stephanie Fagan.

Aranesp and Procrit are man-made versions of a naturally occurring protein that increases production of red blood cells. The drugs are approved to treat the blood disorder anemia when it is caused by chemotherapy and kidney disease.

FDA's meeting did not address use of the drugs in kidney patients. The agency said it would hold a seperate meeting on that issue in the fall.

Aftershocks from the newest recommendations could be felt later this year as the Center for Medicare and Medicaid Services reconsiders when and how much it pays for anemia drugs. The agency, which provides health care to more than 80 million Americans, has said it will use FDA's analysis of the drugs' safety in its reassessment.

Medicare officials have already told local plan providers they can stop paying for Aranesp and Procrit when used in cancer patients who are not on chemotherapy because that use is not government approved. Amgen said last month that action alone would probably cost the company $500 million in sales this year.

While it's difficult to predict what additional payment changes might be made, analysts worry the agency could stop paying for the drugs under certain circumstances. Medicare officials are scheduled to release preliminary guidelines in September.

FDA issues new warnings on anemia drugs

Fri, 09 Mar 2007 00:00:00 -0800

Federal health officials issued stern new warnings Friday for doctors to more carefully prescribe widely used anemia drugs that can increase the risk of death and other serious problems in patients with cancer and kidney disease.

At issue are drugs sold under the brand names Procrit, Epogen and Aranesp. These drugs are genetically engineered versions of a natural protein, erythropoietin, that increases the number of red blood cells.

Anemia is common with certain forms of kidney disease, especially once a patient is on dialysis, and when cancer patients take chemotherapy.

But the Food and Drug Administration pointed to recent studies that found using too much of the drugs increased the risk of death, blood clots, strokes and heart attacks in patients with chronic kidney failure. In other studies, patients with head and neck cancer had more rapid tumor growth if they used higher-than-recommended doses.

Even when the anemia drugs were used at FDA-recommended doses, giving them to cancer patients not on chemotherapy increased the risk of death, the agency warned. Moreover, some doctors have begun giving the drugs to patients following orthopedic surgery, also increasing the risk of blood clots, FDA said.

Friday, the agency added stern warnings to each of the drug's labels urging that:

doctors monitor patients' levels of red blood cells and use the lowest possible dose to avoid the need for blood transfusions.
doctors and patients carefully weigh the risks of using anemia drugs vs. the risk of a transfusion if anemia gets too bad.

Amgen Inc. and Johnson & Johnson, companies that manufacture and market the drugs, both said they would work to inform doctors about the new warnings, outlined in a so-called "black box." The warnings are the most serious a drug label can bear.

"Amgen is committed to providing timely and appropriate communications to physicians and patients whenever we become aware of new safety information that could affect clinical practice," said Dr. Roger Perlmutter, Amgen' s executive vice president of research and development.

The FDA also said it would take a new look at how the drugs are marketed, including claims they can improve the quality of life of cancer patients. The Web site for Procrit, for example, says the drug "helps you find the strength you need."

"With the new label being revised today, we will certainly evaluate any marketing claims and revise them as needed," said Stephanie Fagan, a spokeswoman for J&J's Ortho Biotech Products LP.

A panel of FDA advisers is scheduled to discuss the drugs at a May 10 meeting. Their recommendations could lead to further revisions of the drugs' labels, FDA officials said.

In December, lawmakers and some experts raised concerns that Medicare's payment system encouraged overuse of Epogen, endangering patient lives and wasting taxpayer money. FDA officials said they would forward the recent data on the class of drugs to the Centers for Medicare and Medicaid Services.

The three drugs are huge sellers, with combined 2006 U.S. sales of $10 billion, according to IMS Health Inc.

FDA Strengthens Safety Information for Erythropoiesis-Stimulating Agents (ESAs)

Fri, 09 Mar 2007 00:00:00 -0800

The U.S. Food and Drug Administration (FDA) today issued a public health advisory outlining new safety information, including revised product labeling about erythropoiesis-stimulating agents (ESAs), widely-used drugs for the treatment of anemia. The drugs affected by the safety update are darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). (ESAs are genetically engineered forms of the naturally occurring human protein, erythropoietin. Natural erythropoietin is made by the kidney and increases the number of red blood cells).

FDA and the manufacturer of these products have agreed on revised product labeling that includes updated warnings, a new boxed warning, and modifications to the dosing instructions. The new boxed warning advises physicians to monitor red blood cell levels (hemoglobin) and to adjust the ESA dose to maintain the lowest hemoglobin level needed to avoid the need for blood transfusions. Physicians and patients should carefully weigh the risks of ESAs against transfusion risks.

Recently completed studies describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses. In other studies, more rapid tumor growth occurred in patients with head and neck cancer who received these higher doses.

In studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopedic surgery.

"The agency is in the process of re-evaluating the safety of Aranesp, Epogen, and Procrit on the basis of the results of recent clinical studies," said Steven Galson, M.D. director of FDA's Center for Drug Evaluation and Research. "The new studies provide significant new information for both prescribers and patients, and the new information applies to all ESAs, which share the same mechanism of action. The safety of these products will be discussed when the Oncologic Drugs Advisory Committee (ODAC) meets in May and further revisions to the labeling may occur after that meeting."

Safety concerns from earlier ESA studies were discussed during a 2004 meeting of the ODAC. Product labeling was previously revised in 1997, 2004, and 2005 to reflect new safety information.

The three drugs are approved to treat anemia in patients with chronic kidney failure and in patients with cancer whose anemia is caused by chemotherapy. Epogen and Procrit are approved for patients scheduled for major surgery to reduce potential blood transfusions and for the treatment of anemia due to zidovudine therapy in HIV patients. ESAs are not approved to treat the symptoms of anemia including fatigue in cancer patients, surgical patients, or those with HIV.

All three drugs are manufactured by Amgen Inc. of Thousand Oaks, California. Procrit is marketed and distributed by Ortho Biotech LP, a subsidiary of Johnson & Johnson.

FDA Warns of Serious Side Effects Related to Popular Anemia Drugs

Fri, 09 Mar 2007 00:00:00 -0800

FDA Warns of Serious Side Effects Related to Popular Anemia DrugsThe U.S. Food and Drug Administration (FDA) has issued a new warning about erythropoiesis-stimulating agents (ESAs), which are drugs that are used to treat anemia. The warnings relate to darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). All three of the drugs are made by Amgen Inc., although Procrit is distributed and marketed by a Johnson & Johnson subsidiary.

“Recently completed studies describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses,” the FDA said. “In other studies, more rapid tumor growth occurred in patients with head and neck cancer who received these higher doses.

“In studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopedic surgery.”

This new labeling change marks the fourth time in the past decade that the products’ label warnings were forced to be updated. “The agency is in the process of re-evaluating the safety of Aranesp, Epogen, and Procrit on the basis of the results of recent clinical studies,” said Dr. Steven Galson, director of FDA’s Center for Drug Evaluation and Research. “The new studies provide significant new information for both prescribers and patients, and the new information applies to all ESAs, which share the same mechanism of action. The safety of these products will be discussed when the Oncologic Drugs Advisory Committee (ODAC) meets in May and further revisions to the labeling may occur after that meeting.”

The FDA is asking the drug makers to add a black-box warning, the agency’s most serious alert, that “advises physicians to monitor red blood cell levels (hemoglobin) and to adjust the ESA dose to maintain the lowest hemoglobin level needed to avoid the need for blood transfusions.”

According to the FDA, ESAs are “genetically engineered forms of the naturally occurring human protein, erythropoietin.” Erythropoietin is produced by the kidneys and increases red-blood-cell levels. Currently, the FDA has approved these drugs for treating anemia in patients with chronic kidney failure and in patients whose anemia is a result of chemotherapy. Combined domestic sales of the three drugs reached approximately $10 billion last year alone.

In January, Amgen sent a letter to medical professionals warning them of an elevated risk of fatalities associated with the use of Aranesp in cancer patients. Amgen conducted a clinical trial to test the safety and efficacy of Aranesp on patients whose anemia was caused by the cancer itself, not by chemotherapy. While the drug is not currently approved for this usage, corporate estimates say that approximately 10 to 12 percent of all Aranesp sales are for that exact off-label (unapproved) usage.

The safety of Epogen has also been questioned by the medical community. Last November, two studies in the New England Journal of Medicine cited the overuse of anemia drugs in the treatment of kidney patients. Scientists have found that anemic kidney patients are susceptible to heart problems or death when aggressively treated with these drugs. Epogen has also been under attack by Congress because of the strain it places on Medicare. Anemia drugs are currently Medicare’s largest drug expenditure.

Anemia Drugs Procrit & Epogen May Do More Harm Than Good

Thu, 30 Nov 2006 00:00:00 -0800

Two studies in the New England Journal of Medicine this month have called into question the overuse of drugs in the treatment of anemia in kidney patients. The two most popular anemia drugs, Amgen’s Epogen and Johnson and Johnson’s Procrit are at the center of the controversy, as researchers try to determine whether they’ve been over-prescribed by medical professionals. Sales of anemia drugs are approaching $10 billion annually.

Scientists have found that anemic kidney patients are susceptible to heart problems or death when aggressively treated with these drugs. The drugs are intended to boost hemoglobin in anemic patients, but the increase in hemoglobin is apparently associated with other serious risks.

Before the advent of these anemia treatments, patients had to undergo transfusions to keep their red blood cell counts at healthy levels. The new drugs have been very successful in boosting red blood cell counts, but the fear today is that doctors have become too reliant on the drugs and that they aren’t sufficiently aware of the risks related to boosting hemoglobin (a main component of red blood cells) in kidney patients, which can include heart attack, stroke, and high blood pressure.

Also at issue is Medicare’s payment structure for the anemia drugs. The drugs are currently an enormous profit generator for dialysis clinics around the country. Most dialysis patients receive the drugs, and the drugs generate significantly more cash for the clinics than the dialysis treatments themselves.

Earlier this month, the Boston Globe reported that California Congressmen Bill Thomas and Pete Stark, both members of the House Ways and Means committee, wrote a letter to Medicare, accusing it of failing to “stem the systemic abuse of Epogen, resulting in costs to taxpayers and potential health dangers to patients.” Epogen is Medicare’s largest drug expenditure.

Procrit Anemia Drug Heart Problem Death Attorney

Thu, 30 Nov 2006 00:00:00 -0800

Injured by Procrit?

Latest Procrit Drug Warning

On November 30, 2006, reports came out that two studies in this month’s New England Journal of Medicine have called into question the overuse of drugs in the treatment of anemia in kidney patients. Johnson & Johnson’s Procrit and Amgen’s Epogen are the two most popular anemia drugs which are at the center of the controversy, as researchers try to determine whether they’ve been over-prescribed by medical professionals. Sales of anemia drugs are nearing $10 billion annually. Procrit (Generic: Epoetin alfa) was granted approval in 1999 by the FDA.

According to the above studies, Scientists established that anemic kidney patients are susceptible to heart problems or death when aggressively treated with Epogen or other anemia drugs. The drugs are intended to boost hemoglobin in anemic patients, but the increase in hemoglobin is apparently associated with other serious risks. Prior to the arrival of these anemia treatments, patients had to undergo transfusions to keep their red blood cell counts at healthy levels.

These new drugs have been very successful in boosting red blood cell counts, but the fear today is that doctors have become too reliant on the drugs and that they aren’t sufficiently aware of the risks related to boosting hemoglobin (a main component of red blood cells) in kidney patients, which can include heart attack, stroke, and high blood pressure.

Legal help for Procrit Users
If you or a loved has taken Procrit and suffered heart problems or death, please fill out the form at the right for a free case evaluation by a qualified defective drugs attorney.