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WILL THE NEW CROP OF DRUGS RESTORE A MEASURE OF CREDIBILITY TO THE PHARMACEUTICAL INDUSTRY OR MERELY EXPOSE THE PUBLIC TO ANOTHER ROUND OF RUSSIAN ROULETTE? (Part I Fifty Potential Successes)Mar 1, 2005 Introduction:
For the past several months, we have examined a number of problems associated with the pharmaceutical industry including: (a) several potentially unsafe prescription drugs; (b) highly questionable conduct and practices by drug manufacturers; and (c) whether the FDA is truly committed to protecting the public from both of these dangers or simply acting as a pawn of the drug industry.
Very little has happened in the past decade to give the American public any reason to believe that the FDA’s practice of “fast tracking” drugs to market has been anything but a complete failure. In fact, in less than nine years, 17 drugs have been withdrawn from the market. (Tysabri, Vioxx, Duragesic, Ephedra, Baycol, Raplon, Duract, Posicor, Rezulin, Fen-Phen, Pondimin, Redux, Seldane, Hismanal, Propulsid, Lotronix, and Raxar)
This extremely negative track record strongly supports the conclusion that the current drug approval and monitoring process is seriously flawed. It also explains why many experts recommend years of successful marketing before a drug is declared safe. Public Citizen (http://www.citizen.org) now suggests that a seven year waiting period be observed before taking any new drug. What must be remembered is that no drug is completely safe and even the most successful drugs can have serious side effects. Thus, a “risk versus benefit” analysis must be applied in order to make an informed judgment as to whether the potential side effects of a new drug are acceptable or make it more suitable than existing alternatives.
At this point, we would like to present a discussion of 50 new drugs and drugs currently in development which have already demonstrated some measure of success or the potential to be successful in the future. Next month, we will examine a number of new drugs that have not succeeded or that have run into problems either in the research and development process or shortly after their approval.
RECENTLY RELEASED DRUGS
Lyrica, also known as pregabalin, was approved by the FDA on December 31, 2004 to treat neuropathic pain caused by nerve damage from conditions such as diabetes and shingles. Pfizer is currently looking to have it approved for treating pain related to epilepsy as well. While this drug was not approved as a treatment for generalized anxiety as Pfizer originally had hoped, potential annual sales are still estimated to be $1 to $2 billion range. Lyrica is a new drug in an existing class of medications.
Lunesta, manufactured by Sepracor, is the first sleeping pill to be approved by the FDA for long-term use. Approved on December 1, 2004, this new pill is a time-release version of a sleep aid previously sold only outside the United States and, its release here, would allow Sepracor to have a stake in the sleep aid market currently dominated by Ambien.
Unlike other sleeping pills, Lunesta will not restrict users to a seven-to-ten day prescription, making it an attractive option to those who suffer from chronic sleeplessness. It is a new drug within an existing class of medications and is estimated to have potential annual sales of $500 million to $1 billion.
Manufactured by Eli Lilly, this long-awaited successor to Prozac was approved for the treatment of depression on August 4, 2004. Cymbalta, or duloxetine, may prove to be more effective than other existing antidepressants because it works by inhibiting two neurotransmitters instead of one. In addition, Cymbalta is currently being tested to treat of stress-induced urinary incontinence and approval is expected this year under a different brand name. A new drug in an existing class of medications, Cymbalta’s annual sales as both a treatment for depression and urinary incontinence are projected at up to $2 billion.
Approved on November 18, 2004, Tarceva is a promising new cancer drug which extends survival in late-stage, non-small-cell lung cancer by anywhere from 2 to 6.7 months. Manufactured by the tiny OSI Pharmaceuticals and the much larger Genentech and Roche Pharmaceutical companies, Tarceva could have a decent marketing advantage over AstraZeneca’s Iressa due to the extended survival rate in patients. Considered to be a significant advance over existing medications, Tarceva stands to generate annual sales of anywhere from $500 million to $1 billion.
Approved a little over a year ago (2/26/04), Avastin is the first of its kind – an anti-angiogenesis drug which works by starving tumors of the blood they need to survive. This is a dramatic advance over existing therapies.
Avastin, manufactured by Genentech, has yielded encouraging results for colon cancer patients. When accompanied by chemotherapy, Avastin extended survival in patients whose colon cancer had spread to other organs by up to five months. Priced at $4,400 per month, this breakthrough medication has the potential to become the best-selling cancer drug ever with annual sales reaching between $1 and $2 billion.
Erbitux was approved by the FDA on February 12, 2004 for the treatment of patients whose colon cancer has spread to other parts of the body and who have failed other treatments. It can be prescribed alone or in conjunction with chemotherapy. Erbitux, manufactured by Bristol-Meyers Squibb, is also being tested on tumor of the lung, pancreas, head, and neck and is expected to represent a significant advance over existing therapies. Its market potential is placed at $500 million to $1 billion annually.
Alimta, manufactured by Eli Lilly, is the first treatment for lung cancer caused by asbestos exposure. This rare cancer occurs in only 2,000 annually in the U.S. In addition, Alimta may also be effective against the most common form of lung cancer and may have less serious side effects than other available treatments. It is considered to be a significant advance over existing therapies and was approved on February 5, 2004. It is estimated that Alimta could generate $500 million to $1 Billion in annual sales for Eli Lilly.
Ketek, manufactured by Aventis, is a revolutionary new treatment for respiratory bacterial infections. More than one-third of the bacteria that cause pneumonia are resistant to macrolides, a class of antibiotics currently used to treat such infections. Ketek works because it gets around the resistance.
Although some experts remain concerned about heart and liver related risks, Ketek was approved on April 1, 2004 after a two year delay. Sales could reach $500 million to $1 billion annually.
Approved on September 12, 2003, Cubicin, formerly known as Cidecin, was the first antibiotic in a new class to be approved by the FDA in five years. Cubicin treats the drug-resistant bacteria that cause infections in hospitals. Presently, sales estimates for Cubicin remain low (up to $500 million). However, the number could change drastically if Cubicin is also approved for the treatment of heart infections.
Cialis (approved on November 21, 2003), manufactured by Eli Lilly, treats erectile dysfunction by blocking the same enzyme as competitors Levitra and Viagra. Cialis, however, works for up to 36 hours, earning it the nickname “the weekend pill.” For this reason, its annual sales are already between $1 and $2 billion annually and it continues to hold its own against Viagra, which held a monopoly on the field for years.
PROMISING DRUGS IN DEVELOPMENT
Although none of these drugs has gained final approval from the FDA, they appear to be the most promising medicines now under development. (Names in parentheses refer to the drug’s manufacturer unless otherwise indicated).
This compound is a gene-based medication that blocks the enzyme called lipoprotein-associated phospholipase which hangs from cholesterol particles, creating a risk for cardiovascular disease. Glaxo is hopeful the drug will prevent atherosclerosis and heart attacks, making it an important and entirely new class of medications. It is currently in late-stage trials. If approved, sales could reach $500 million to $1 billion annually.
Another prototype class of drugs, Acomplia is designed to help patients lose weight and quit smoking while almost minimizing the risk of heart disease. The drug has had extremely promising preliminary results, cutting 3.5 inches off patients’ waistlines, helping them lose an average of 20 pounds, and doubling their likelihood of quitting smoking within 10 weeks.
Acomplia may also reduce the risk of heart disease by working directly on fat cells. It is expected to be submitted to the FDA for approval later this year and has blockbuster potential in terms of annual sales ($2 billion).
AGI-1067 is the first drug aimed at reducing cardiac inflammation which can cause blood clots which lead to heart attacks. Mid-stage trial results were unclear and inconclusive and this has delayed the application process until Atherogenics can raise the number of patients in a large-scale trial from 4,000 to 6,000. Estimated annual sales are in the $500 million to $1 billion range.
DG031 (DeCode Genetics, Bayer)
Although originally designed to be an asthma treatment, if approved, this drug would be marketed to combat artery inflammation. DeCode has offered evidence that artery inflammation and heart attacks can be attributed to the same genetic mechanism involved in asthma. Second–stage trials were promising and a large-scale final-stage trial is currently in progress. Potential sales are estimated at $500 million to $1billion annually.
This is an experimental medicine that involves injecting good cholesterol (HDL) into the body. It is based on a potent form of HDL cholesterol discovered in a population of Italians outside Milan. In November, a small preliminary trial showed that ETC-216 did cause an unparalleled reduction in the amount of plaque in patients’ arteries but further trials are on hold until next year or whenever Pfizer manufactures more of the protein which is difficult to reproduce. Potential sales could be $500 million to $1 billion annually.
Lipitor is one of the most powerful drugs for reducing bad cholesterol and the best-selling medicine in the world. Adding torcetrapib, which would raise HDL, should only increase its blockbuster status. Pfizer is currently spending $800 million in late-stage trials to prove that the “combo” pill prevents heart attacks (in early studies, high doses raised some patients’ blood pressure). If the drug proves to be successful sales could even exceed $9 billion, Pfizer’s current income from Lipitor.
Pactimibe (Sankyo Pharmaceuticals)
Pactimibe would work differently than existing “statins” Lipitor and Zocor (which inhibit cholesterol production) by keeping cholesterol from sticking to the artery wall (by inhibiting an enzyme called acyl-CoA cholesterol acyl-transferase) (ACAT). Development of a similar drug by Pfizer was halted in 2003 when it failed to perform as intended. If successful, Pactimibe could have annual sales in the $1 billion to $2 billion range.
Other Cardiovascular Drugs on the Horizon
Thelin (Encysive Pharmaceuticals) – A treatment for pulmonary hypertension that is in late-stage trials.
SPP100 (Novartis) – High blood pressure medication in late-stage trials.
PPAR alpha agonist (Eli Lilly, Ligand Pharmaceuticals) – Designed to raise good cholesterol and lower triglycerides. In mid-stage trials.
Exenatide (Amylin Pharmaceuticals, Eli Lilly)
Exenatide, based on a protein found in the saliva of the venomous Gila monster, is an injection which lowers blood sugar when it is too high and is marketed towards those with Type 2 diabetes. A New Drug Application has been accepted by the FDA based on a June 30, 2004 submission and a decision is expected by the end of April 2005. Potential annual sales could be between $500 million and $1 billion.
Exubera (Pfizer, Aventis, Nektar Therapeutics)
Exubera is the first drug of its kind – inhaled insulin. Preliminary trials have shown that it is as effective as injected insulin for both Type 1 and Type 2 diabetes. Concerns about potential pulmonary problems have delayed this drug for a long time. Pfizer reports, however, that a two-year lung function study found little difference between Exubera and injected insulin.
If approved, this drug could revolutionize the market and have potential annual sales of around $2 billion. A New Drug Application could be forthcoming soon. Eli Lilly and Alkermes are currently developing a similar drug. Such a drug could have annual sales between $1 billion and $2 billion.
Galida has the potential to control both cholesterol and blood sugar for patients with Type 2 diabetes. The race to market this type of drug is currently one of the hottest competitions in the industry since such a drug could have annual sales between $1 billion and $2 billion.
Galida may already be fading out of that race, however, since there are concerns about potential kidney problems and two recent studies produced cancer in laboratory animals. These problems have prompted additional testing and a delay in filing a New Drug Application until 2007.
This drug is in a race (with Merck’s MK-0431) to become the first pill to raise the protein called glucagons-like peptide. The benefit of such a drug would be that it would control blood sugar only when it is too high thereby reducing the risk of hypoglycemia. This feature would make the drug a potential blockbuster with annual sales between $1 billion and $2 billion. Novartis should be submitting a New Drug Application to the FDA in 2006.
Merck has been less forthcoming than Novartis with information concerning this revolutionary form of insulin-control drug. However, a New Drug Application is also expected to be filed in 2006.
Muraglitazar (Bristol-Meyers Squibb, Merck)
This drug targets more than one of the cellular signals called peroxisome proliferation activation receptors (PPARs) and could control both cholesterol and blood sugar in Type 2 diabetics. Although there were results of the drug causing cancer in laboratory rats, the drug (which is similar to Galida) was submitted for FDA approval in December 2004.
Cerovive (Renovis, AstraZeneca)
Cerovive represents a completely new paradigm in its field. It has the potential to protect brain cells for up to four, or even six, hours after a stroke by blocking toxic free radicals. While annual sales are projected at only about $500 million, this drug stands to make much more if final-stage trials are highly positive. Even though many such drugs have been tested, only one (Genentech’s tPA) has been approved and it works up to three hours after a stroke.
Clioquinol (Prana Biotechnology)
This Alzheimer’s medication, like others, focuses on proteins that make tangles in the brain which then inhibit mental function. Clioquinol is actually an anti-parasite drug which can help keep copper and zinc from becoming involved in proteins tangle formation. This drug is still a long way off, however.
Gaboxadol (Merck, Lundbeck)
This sleeping pill has the potential to eliminate the problems of addiction that are associated with other sleep aids. Merck has licensed the drug from Danish drug giant Lundbeck, but it probably will not be available until 2006 or 2007. By that time, competitors may be able to beat Merck to market with similar drugs.
Indiplon (Neurocrine Biosciences, Pfizer)
This medication for sleeplessness works in a similar way to Ambien but is ten-times more powerful in clinical trials. It has been submitted to the FDA for approval and a decision is expected this year. Lunesta (above), however, has already been approved and could be on the market soon. Since some 40 million Americans suffer from sleep disorders, this market is particularly attractive to many of the pharmaceutical companies.
Pheserine is designed to improve memory but, like other Alzheimer’s drugs, does not slow the disease’s progression. Some animal data, however, indicates that Phenserine may actually slow the disease to some extent as well. A six-month trial has been completed and the results are due out this month.
Varenicline (Pfizer) – A smoking addiction medication in late-stage trials.
BAY-43-9006 (Onyx Pharmaceuticals, Bayer)
Originally, this drug was designed to neutralize a protein (RAF kinase) which helps cause cells to divide. However, the drug also exhibits the ability to block proteins that responsible for the growth of blood vessels that feed tumors. The drug shows promise as a treatment for kidney cancer which is resistant to most other cancer medications.
In a second-stage trial, the drug shrunk or stabilized tumors in 70% of 202 kidney cancer patients. This figure far exceeds the 15% response rate to existing cancer therapies. As a result, the completion of a final-stage trial involving 800 kidney cancer patients is being eagerly awaited to see if this drug offers an increased life expectancy over a placebo. If all goes well, this promising drug could be on the market sometime in 2006. Since it is a limited application drug, its potential annual sales would probably be up to $500 million.
BMS-354825 (Bristol-Meyers Squibb)
Although Gleevec (Novartis) has been very successful in the treatment of chronic myelogenous leukemia (CML), a disease that causes uncontrollable production of certain white blood cells, many patients eventually develop resistance to the drug. This new medication, however, showed promise in an early-stage test when it normalized white blood cell counts in 31 of 36 leukemia patients who were unable to be treated with Gleevec. BMS-354825 attacks five “bad” proteins including the one (BCR/ABL) that goes awry in CML.
Second-stage trials have recently started. This drug, like some of the other cancer medications, will have narrow application if approved. This would limit its potential annual sales to the $500 million range. It should be noted that Novartis is working on a successor to Gleevec called AMN107.
CP-675,206 (Pfizer, Abgenix) and
MDX-010 (Medarex, Bristol-Meyers Squibb)
Both of these drugs are potentially significant advances in the science of activating the body’s “killer” T-cells to seek out and destroy cancer cells. This type of drug is called a monoclonal antibody. In early testing, each of these medications produced dramatic shrinkage in some patients with advanced melanoma, the most serious type of skin cancer. CP-675,206 has recently entered second-stage testing while MDX-010 is already in final-stage testing. As with other limited application drugs the potential annual sales are estimated to be in the $500 million range.
Difficult cancers require several genes to be targeted at the same time. This drug is designed to do just that with respect to breast, bladder, and other cancers by combining the mechanisms of two existing drugs (Iressa and Herecptin) into a single pill. Final-stage testing is in progress and a New Drug Application could be filed by the end of 2005. This drug could be in the $500 million to $1 billion annual sales range.
Other Promising Cancer Drugs in Late-Stage Testing
Telcyta (Telik) – Ovarian cancer treatment.
SU11248 (Pfizer) – Stomach cancer treatment.
Revlimid (Celgene) – Treatment for myelodysplastic syndromes.
Provenge (Denderon) – Prostate cancer treatment.
PTK-787 (Novartis) – Colon cancer treatment.
Panitumumab (Abgenix, Amgen) – Treatment for colon cancer and other tumors.
Miscellaneous Drugs in Late-Stage Trials or Awaiting FDA Approval
Abatacept (Bristol-Meyers Squibb)
This drug is designed to treat rheumatoid arthritis by the novel mechanism of preventing the activation of immune system T-cells. It is seen as an alternative for patients who failed to respond to existing RA drugs such as Enbrel. The drug is currently under review by the FDA but how it will be positioned in the highly competitive area of RA medications remains to be seen.
AMG 162 (Amgen)
Osteoporosis is now a $4 billion “market” and growing every year as the “baby boomer” generation reaches 50 and over. Right now, Merck’s Fosamax is the undisputed leader in sales. AMG162 may help restore the body’s own bone-maintaining mechanisms. Unlike some other osteoporosis drugs that can cause gastrointestinal side effects, Amgen’s drug might only need to be given twice a year. If successful, potential annual sales could be in the $1 billion to $2 billion range. However, this drug is still several years away.
With bacteria becoming increasingly resistant to even the strongest antibiotics (like vancomycin), a new approach is needed. This novel antibiotic is used to treat bloodstream infections such as Staphylococcus aureus (a hospital killer) and other serious bacterial infections. It even outperformed vancomycin in treating bloodstream infections. Vicuron expects to file for FDA approval to treat skin and soft-tissue infections by the end of 2005.
HPV Vaccine (Merck)
The human papilloma virus (HPV) is responsible for causing 70% of all cervical cancer cases. Each year, 4,000 women die from cervical cancer in the United States alone. In a mid-stage trial, this vaccine (which represents a potentially new paradigm) prevented infection in every woman who received it (as opposed to a 4.1% infection rate for women taking the placebo). Since the vaccine would need to be administered before a child became sexually active, parents would have to take an active role in seeing that this is done. HPV vaccine has the potential for annual sales in the $500 million to $1 billion range.
Lucentis (Genentech, Novartis)
Macular degeneration is an age-related disorder that afflicts 10 million people and is the leading cause of blindness in older Americans. Since the baby boomer generation has swelled the percentage of the population over 50, this disease is rapidly on the rise.
Lucentis works by blocking the buildup of blood vessels in the eyes of those who have the bad (wet) form of macular degeneration which represents about 10% of the total number of those afflicted. Lucentis is in late-stage testing but, even if approved, it would have a limited market (up to $500 million in annual sales) as a result of stiff competition from Pfizer’s recently approved Macugen.
This intravenous antibiotic is a bacteria killer with great potential. It is a significant advance in the class of drugs known as glycyclines and may be effective against a wide spectrum of bacteria. Presently, Tygacil is anticipated as a treatment for skin and abdominal infections. It has been under review (for approval) by the FDA and other regulatory agencies worldwide since December15, 2004. Sales could be in the $500 million to $1 billion range or higher.
UK-427, 857 (Pfizer)
There is no secret about the fact that new drugs are desperately needed to combat resistant strains of HIV. One drug, Fuzeon (Roche), while effective, is extremely expensive and must be injected. UK-427,857 is a revolutionary pill that blocks the HIV virus' ability to enter immune system cells. It is one of a new class of compounds called CCR5 inhibitors. (CCR5 is a receptor on immune cells that HIV receptors dock with.) The drug appears to be effective against resistant strains of the virus and is currently in final-stage trials. Two other companies, Shering-Plough and GlaxoSmithKline, are also in human trials with similar drugs and may only be slightly behind Pfizer in this race.
These 50 drugs represent the best of the crop of new drugs which have been recently approved or which are getting close to the application stage. While every pharmaceutical expert and public watchdog organization hopes all of these drugs will be able to safely and successfully treat the conditions they were designed for, the reality is that many of them will either fail to reach or fall short of that goal.
In at least some of these cases the drug will turn out to have dangerous side effects which will require it to be pulled from the market or be labeled with a “black box” warning. As in the case of Tysabri (see next month’s Newsletter), a promising MS drug which was on the market for only four months before being pulled, short-term success will give way to failure once the drug is put to the test of long-term use by a wide range of actual patients. The “fast tract” approval system and lack of longitudinal trials during most testing phases make it impossible to predict what the ultimate fate of a drug will be. Some of the most highly anticipated remedies have gone from “miracle drug” or “blockbuster” to public health catastrophe in a matter of months, weeks, or even days.
Hundreds of millions of dollars are bet every year on the potential success of new drugs with the goal of reaping billions of dollars in profits. This high stakes balance-sheet approach to marketing produces everything from misleading advertising to questionable testing and reporting procedures.
Sadly, the public is the final test subject for every one of these gambles. As a result, innocent, trusting, and desperate patients become little more than laboratory animals. Catastrophic injuries and death are regarded as collateral damage and paying for such harm is regarded as a necessary operating expense. This is precisely why the FDA must be above reproach and fully committed to protecting the public’s health and safety. Regrettably, as we have repeatedly pointed out in previous Newsletters, this is not nearly the case.
As always, we here at Parker & Waichman hope that this information has been of help to our clients and subscribers. If you have questions regarding a potential case involving any prescription drug, do not hesitate to contact us at http://www.yourlawyer.com. Next month we will examine a number of new drugs that have recently been pulled from the market or that have fallen short of expectations while in development.