September 2008

Process Validation Guidance to Focus on Testing Upfront

FDA News Source

The FDA will emphasize more oversight and batch testing in the early stages of drug commercialization in its revised guidance on process validation, according to Brian Hasselbalch, a consumer safety officer in CDER’s Division of Manufacturing and Product Quality.

Prescription Drug Advertising Subject of New FDA Web Site for Consumers

PR News Wire Source

EthicAd, a nonprofit organization devoted to improving public health through consumer education, announces the launch of a new FDA Web site created to help the general public better understand direct-to-consumer (DTC) advertising of prescription medications. The site, "Be Smart About Prescription Drug Advertising," is hosted by the FDA's Center for Drug Evaluation and Research and was developed by the FDA in partnership with EthicAd. For details, visit EthicAd.

Michael S. Shaw, M.D., executive director of EthicAd, notes that the primary goal of the new site is to help the public obtain accurate, science-based information about prescription drugs and to understand the role and nature of DTC advertising.

"People are often confused about DTC advertising, which is one of the most controversial areas of pharmaceutical marketing," Shaw says. "FDA's new Web site helps clarify the issues by outlining the different types of DTC advertising, explaining what information people should expect to see in DTC ads, and what additional information they should seek out about advertised products."

The easy-to-navigate site includes a practical "Ask Yourself" checklist summarizing information consumers should obtain in order to have knowledgeable conversations with their physicians about advertised products. The new Web site also includes a section for public feedback, which will be used to shape the direction of future FDA consumer-oriented initiatives.

"We share the FDA's commitment to developing innovative and relevant education programs," Shaw says. "By helping consumers obtain factual and reliable information about prescription drugs and have empowered conversations with their healthcare providers about treatment options, EthicAd and the FDA hope to improve individual patient outcomes as well as improve the public health at large."

EthicAd is a volunteer nonprofit organization whose goal is maximizing the public health benefits of DTC advertising by promoting the development of ads that provide substantive, understandable and reliable information about pharmaceutical products. The organization was founded by noted heart surgeon and Congressional Gold Medal recipient Dr. Michael E. DeBakey.

EthicAd does not receive any funding from the pharmaceutical industry.

FDA to List Drugs Under Review for Safety Issues

Wall Street Journal Source Wave 3 Source

Conference with Gerald Dal Pan, M.D., M.P.H., director, Office of Surveillance and Epidemiology, CDE and Paul Seligman, M.D., M.P.H., associate director of Safety Policy and Communication, CDER, both with U.S. FDA

The U.S. Food and Drug Administration has started listing on its Web site drugs being evaluated for potential safety issues, the agency said Friday.

"If a drug appears on a quarterly report, it means we have begun analysis to determine whether there is a safety problem that requires further evaluation," Dr. Gerald Dal Pan, director of the FDA's Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, said during a Friday teleconference.

This information is being posted as part of the 2007 Food and Drug Administration Amendments Act. Under the act, the agency must post quarterly information on potential drug risks, based on the agency's review of adverse-event reports submitted by doctors.

The list contains only the drug's name and the potential problem associated with it; it doesn't reveal the extent of the problem or how many adverse reports have been filed.

The list also doesn't include all the drugs the FDA is currently reviewing for safety problems, Dal Pan said. "This list is derived from issues identified in the adverse-event reporting system," he said.

The current list covers January to March 2008. The appearance of a drug on the list doesn't mean the FDA has concluded that there's a problem with it. A drug only appears on the list because the agency has identified a potential safety problem, Dal Pan said.

The initial list, released Friday on the Web site, includes 20 drugs. The drugs range from the anesthetic Desflurane, which has been linked to cardiac arrest, to nitroglycerin (Nitrostat) which is used to treat angina. A confusing label could result in overdose, the agency said. Other drugs on the list include natalizumab (Tysabri), which is used to treat multiple sclerosis and Crohn's disease and has been linked to melanoma, and telbivudine (Tyzeka), which treats hepatitis B and has been linked to damage to the nervous system, the FDA said.

The list includes a wide array of drugs, from Eli Lilly & Co.'s antidepressant Cymbalta to Purdue Pharma LP's painkiller Oxycontin. It also addresses a range of adverse reactions, including cardiac arrest, cancer and Purple Glove Syndrome, which can result in patients having their arms amputated. (See the FDA's list of drugs that are under investigation.)

Drugs under investigation before 2008 or after March aren't included on the current list. Dal Pan said he wasn't sure when an updated list would be posted.

FDA officials emphasized that people taking drugs on the list should not overreact and stop taking them.

"As always, we are very sensitive to the potential misinterpretation or over-interpretation of any potential unintended consequences because the drug is on the list," Dr. Paul Seligman, the associate director of Safety Policy and Communication at the FDA's Center for Drug Evaluation and Research, said during the teleconference.

"There is always the risk that anytime you put something in writing and post it on an official FDA Web site that people will read into it more than that we are just conducting a review," Seligman said. "We are expecting people not to take actions simply based on the fact that we are evaluating a particular drug."

In addition to providing the public with more information, the agency thinks the list will encourage more reporting of adverse events.

M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals

FDA Source

Updated draft

FDA Bioequivalence Guidelines Updated for Several Drugs

FDA News Source

The FDA has updated its bioequivalence guidelines for several drugs as part of an effort to develop a full set of online product-specific bioequivalence recommendations that generic drug applicants can use instead of submitting requests for assistance in bioequivalence study design.

Amrubicin Receives FDA Fast Track Designation for the Treatment of Small Cell Lung Cancer after First-Line Chemotherapy

Amrubicin Receives FDA Fast Track Designation for the Treatment of Small Cell Lung Cancer after First-Line Chemotherapy SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ: CELG) today announced that Amrubicin has been granted Fast Track product designation by the U.S. Food and Drug Administration (FDA) for the treatment of small cell lung cancer after first-line chemotherapy. A drug designated as a Fast Track product is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to provide a therapy where none exists or provide a therapy which may offer a significant improvement in safety and/or effectiveness over existing therapy. Fast track designation, which was authorized by the FDA Modernization Act of 1997, can potentially facilitate development and expedite the review of an approval application. This fast track status is meant to bring valuable new treatments to the patient earlier. “This designation is another example of the increasing focus on the clinical potential of Amrubicin as a treatment for small cell lung cancer,” said Graham Burton M.D., SVP, Global Regulatory Affairs and Pharmacovigilance for Celgene Corporation. “It further validates the considerable scientific data being presented at major medical meetings for this critical disease.” About Amrubicin Amrubicin is a third-generation, synthetic anthracycline analogue that has demonstrated substantial clinical efficacy in the treatment of small cell lung cancer. Amrubicin is a potent topoisomerase II inhibitor and is being studied as a single agent and in combination with anti-cancer therapies for a variety of solid tumors, including lung cancer. Amrubicin is currently approved and marketed in Japan for the treatment of lung cancer by Nippon Kayaku, a Japanese pharmaceutical firm focused on oncology, which licensed Japanese marketing rights from Dainippon Sumitomo Pharma, the original developer of the therapy. Dainippon Sumitomo Pharma also licensed the North American and European Union rights of Amrubicin to Pharmion Corporation, which was acquired by Celgene Corporation in March 2008. Amrubicin has been granted orphan-drug designation for the treatment of small cell lung cancer in both the U.S. and European Union. About Small Cell Lung Cancer Small cell lung cancer is a disease in which malignant cells form in the tissues of the lung, and which occurs almost exclusively in people who smoke. While small cell lung cancer constitutes approximately 15 percent of all lung cancers, SCLC tends to be more aggressive and fast growing than the more common non-small cell lung cancer. An estimated 65,000 patients are diagnosed with SCLC each year in the US and EU. About Celgene Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

Business Wire Source

Celgene Corporation (NASDAQ: CELG) today announced that Amrubicin has been granted Fast Track product designation by the U.S. Food and Drug Administration (FDA) for the treatment of small cell lung cancer after first-line chemotherapy.

A drug designated as a Fast Track product is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to provide a therapy where none exists or provide a therapy which may offer a significant improvement in safety and/or effectiveness over existing therapy. Fast track designation, which was authorized by the FDA Modernization Act of 1997, can potentially facilitate development and expedite the review of an approval application. This fast track status is meant to bring valuable new treatments to the patient earlier.

“This designation is another example of the increasing focus on the clinical potential of Amrubicin as a treatment for small cell lung cancer,” said Graham Burton M.D., SVP, Global Regulatory Affairs and Pharmacovigilance for Celgene Corporation. “It further validates the considerable scientific data being presented at major medical meetings for this critical disease.”

Amrubicin is a third-generation, synthetic anthracycline analogue that has demonstrated substantial clinical efficacy in the treatment of small cell lung cancer. Amrubicin is a potent topoisomerase II inhibitor and is being studied as a single agent and in combination with anti-cancer therapies for a variety of solid tumors, including lung cancer.

Amrubicin is currently approved and marketed in Japan for the treatment of lung cancer by Nippon Kayaku, a Japanese pharmaceutical firm focused on oncology, which licensed Japanese marketing rights from Dainippon Sumitomo Pharma, the original developer of the therapy. Dainippon Sumitomo Pharma also licensed the North American and European Union rights of Amrubicin to Pharmion Corporation, which was acquired by Celgene Corporation in March 2008. Amrubicin has been granted orphan-drug designation for the treatment of small cell lung cancer in both the U.S. and European Union.

Small cell lung cancer is a disease in which malignant cells form in the tissues of the lung, and which occurs almost exclusively in people who smoke. While small cell lung cancer constitutes approximately 15 percent of all lung cancers, SCLC tends to be more aggressive and fast growing than the more common non-small cell lung cancer. An estimated 65,000 patients are diagnosed with SCLC each year in the US and EU.

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

FDA staff note deaths in Pfizer bone drug study

Reuters Source

Osteoporosis patients who received a low dose of an experimental Pfizer Inc pill were more likely to die within five years than others who got a placebo, U.S. drug reviewers said in an analysis released on Thursday.

An increased death rate for women given the highest dose of the Fablyn drug was not statistically significant in the company study and therefore could have been due to chance, Food and Drug Administration reviewers said.

The drug, which the FDA rejected for osteoporosis in 2005, was developed with technology from Ligand Pharmaceuticals Inc.

The FDA staff also said it was "of concern" that Fablyn patients had more than double the chance of developing a blood clot in a vein. Blood clots are a known risk of similar drugs.

The agency will ask a panel of outside advisers that meets on Monday if Fablyn offers acceptable safety, the staff summary said. The reviewers said the once-a-day pill was effective for preventing fractures in post-menopausal women with osteoporosis, which weakens bones.

Pfizer said in a separate summary: "Overall (Fablyn) was not associated with an increased mortality risk."

The higher rate seen for the low-dose patients "appears to be due to an unusually low mortality rate in the placebo group" in people treated in Mexico and in Central and South America, Pfizer said. Nearly 80 percent of patients were in other regions.

The causes of death were consistent with the leading killers of elderly people, including cancer and heart disease, Pfizer said.

Fablyn belongs to a class of drugs known as selective estrogen receptor modulators, or SERMs, which includes Eli Lilly and Co's osteoporosis drug Evista.

Pfizer said Fablyn "affords a unique benefit among SERMs" by reducing more types of fractures.

The FDA will weigh the advisory panel's input before deciding whether to approve Fablyn. The agency usually follows panel recommendations, but is not required to.

The drug's generic name is lasofoxifene. The previous proposed brand name was Oporia.

If the drug is approved, Ligand will receive a milestone payment and royalties of 3 percent of net sales.

Pfizer shares fell 1.5 percent to $18.92 in afternoon New York Stock Exchange trading, while Ligand dropped 2 cents to $3.32 on Nasdaq.

FDA orders stronger warnings for 4 arthritis drugs

AP Source

The Food and Drug Administration ordered stronger warnings Thursday on four medications widely used to treat rheumatoid arthritis and other serious illnesses, saying they can raise the risk of possibly fatal fungal infections.

The drugs - Enbrel, Remicade, Humira and Cimzia - work by suppressing the immune system to keep it from attacking the body. For patients with rheumatoid arthritis, the treatment provides relief from swollen and painful joints, but it's "a double-edged sword," said the FDA's Dr. Jeffrey Siegel. That's because the drugs also lower the body's defenses to various kinds of infections.

Siegel, who heads the office that oversees arthritis drugs, said the FDA became concerned after discovering that doctors seemed to be overlooking a particular kind of fungal infection called histoplasmosis. Of 240 cases reported to the FDA in which patients taking one of the four drugs developed this infection, a total of 45 died - about 20 percent.

The infection, which mimics the flu, is prevalent in much of the middle part of the country. It can have particularly grave consequences if it isn't caught early and spreads beyond the respiratory system to other organs of the body.

Siegel said the investigation began with a single case of a woman taking one of the drugs who died of histoplasmosis. Delving into the case, doctors at the FDA found that the woman had been sick with the fungal infection for a long time. "This case led us to be concerned that there may be other situations in which physicians may not recognize histoplasmosis," said Siegel.

FDA officials searched the agency's database and found the 240 cases of patients taking the medications who had also developed the fungal infection. Of those, at least 21 appeared to involve a late diagnosis, and 12 of them - more than half - ultimately died.

Siegel said the FDA's order Thursday means that the risk of histoplasmosis will be flagged in a "black box," the strongest warning information in a drug's prescribing literature. The four medications already have black box warnings about the risk of infections, but the language varies from drug to drug.

Patients should call their doctors if they develop persistent fever, cough, shortness of breath or fatigue, which can be signs of the fungal infection.

And the FDA is also urging doctors to consider aggressive use of antifungal drugs in patients who develop such symptoms, even if the infection has not been confirmed by a laboratory test. Siegel said such a decision should not be taken lightly, since antifungal drugs can also have dangerous side effects. Doctors should consider stopping treatment with the immune-suppressing drugs if patients develop infections.

The four drugs belong to a class known as TNF-alpha blockers, and are considered a mainstay for treating rheumatoid arthritis, a disabling disease in which the immune system attacks the joints. They are also used to treat Crohn's disease, juvenile arthritis, certain types of psoriasis, and other immune system disorders. All are taken by injection.

Separately, the FDA is investigating a possible link between the four medications and cancer in young patients. The agency said earlier this year it has received 30 reports of cancers, mainly lymphomas, in patients who began taking the medications when they were 18 or younger. That investigation is expected to take the rest of the year.

Three of the drugs, Enbrel, Humira and Remicade, are considered blockbusters, with sales of over $1 billion annually for each. Cimzia is newer and less widely used.

Humira is made by North Chicago, Ill.-based Abbott Laboratories Inc; Cimzia by Belgium-based UCB; Enbrel by Thousand Oaks, Calif.-based Amgen Inc. and Madison, N.J.-based Wyeth; and Remicade by Horsham, Pa.-based Centocor, a unit of Johnson & Johnson.

Abbott shares fell $1.29, or 2.3% to $56.64 Thursday afternoon; Amgen fell $1.73, or 2.7 percent, to $61.37; Wyeth fell $1.12, or 2.6 percent to $41.47; and Johnson & Johnson fell 79 cents to $70.73.