Regulatory Blog and News

FDA Takes New Regulatory Action Against Ranbaxy’s Paonta Sahib Plant in India

FDA Source

Agency halts review of drug applications from plant due to evidence of falsified data; invokes Application Integrity Policy

The U.S. Food and Drug Administration today announced that a facility owned by India-based Ranbaxy Laboratories falsified data and test results in approved and pending drug applications. The facility, Paonta Sahib, has been under an FDA Import Alert since September 2008.

The FDA is continuing to investigate this matter to ensure the safety and efficacy of marketed drugs associated with Ranbaxy’s Paonta Sahib site. To date, the FDA has no evidence that these drugs do not meet their quality specifications and has not identified any health risks associated with currently marketed Ranbaxy products.

In the meantime, the FDA recommends that patients not disrupt their drug therapy because this could jeopardize their health. Individuals who are concerned about their medications should talk with their health care professional.

The affected applications are for drugs that fall into three categories:

* Approved drugs made at the Paonta Sahib site for the U.S. market;

* Drugs pending approval at the FDA that are not yet marketed; and

* Certain drugs manufactured in the United States that relied on data from the Paonta Sahib facility.

“Companies must provide truthful and accurate information in their marketing applications,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research (CDER). “The American public expects and deserves no less.”

To address the falsified data, the FDA has invoked its Application Integrity Policy (AIP) against the Paonta Sahib facility. The AIP is invoked when a company’s actions raise significant questions about the integrity of data in drug applications. This AIP covers applications that rely on data generated by the Paonta Sahib facility only.

Under the AIP, the FDA has asked Ranbaxy to cooperate with the agency to resolve the questions of data integrity and reliability. This would include implementing a Corrective Action Operating Plan (CAOP) to provide assurance of the integrity and reliability of data from the Paonta Sahib facility. A CAOP includes, but is not limited to, conducting a third-party independent audit of applications associated with Paonta Sahib.

When the AIP is implemented, the FDA stops all substantive scientific review of any new or pending drug approval applications that contain data generated by the Paonta Sahib facility.

“The FDA’s investigations revealed a pattern of questionable data raising significant questions regarding the reliability of certain applications, and this warrants applying the Application Integrity Policy,” said Deborah Autor, director of CDER’s Office of Compliance. “Today’s action reflects the FDA’s continued vigilance and its steadfast commitment to safeguarding the public’s health.”

On Sept. 16, 2008, the FDA issued two warning letters and instituted an Import Alert barring the entry of all finished drug products and active pharmaceutical ingredients from Ranbaxy’s Dewas, Paonta Sahib and Batamandi Unit facilities due to violations of U.S. current Good Manufacturing Practices requirements. That action barred the commercial importation of 30 different generic drugs into the United States and remains in effect.

FDA Requires Boxed Warning and Risk Mitigation Strategy for Metoclopramide-Containing Drugs

FDA Source

Agency warns against chronic use of these products to treat gastrointestinal disorders

The U.S. Food and Drug Administration announced today that manufacturers of metoclopramide, a drug used to treat gastrointestinal disorders, must add a boxed warning to their drug labels about the risk of its long-term or high-dose use. Chronic use of metoclopramide has been linked to tardive dyskinesia, which may include involuntary and repetitive movements of the body, even after the drugs are no longer taken.

Manufacturers will be required to implement a risk evaluation and mitigation strategy, or REMS, to ensure patients are provided with a medication guide that discusses this risk.

“The FDA wants patients and health care professionals to know about this risk so they can make informed decisions about treatment,” said Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “The chronic use of metoclopramide therapy should be avoided in all but rare cases where the benefit is believed to outweigh the risk.”

Current product labeling warns of the risk of tardive dyskinesia with chronic metoclopramide treatment. The development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time.

Tardive dyskinesia is characterized by involuntary, repetitive movements of the extremities, or lip smacking, grimacing, tongue protrusion, rapid eye movements or blinking, puckering and pursing of the lips, or impaired movement of the fingers. These symptoms are rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.

Metoclopramide works by speeding up the movement of the stomach muscles, thus increasing the rate at which the stomach empties into the intestines. It is used as a short-term treatment of gastroesophageal reflux disease in patients who have not responded to other therapies, and to treat diabetic gastroparesis (slowed emptying of the stomach’s contents into the intestines). It is recommended that treatment not exceed three months.

Metoclopramide is available in a variety of formulations including tablets, syrups and injections. Names of metoclopramide-containing products include Reglan Tablets, Reglan Oral Disintegrating Tablets, Metoclopramide Oral Solution, and Reglan Injection. More than two million Americans use these products.

Recently published analyses suggest that metoclopramide is the most common cause of drug-induced movement disorders. Another analysis of study data by the FDA showed that about 20 percent of patients in that study who used metoclopramide took it for longer than three months. The FDA has also become aware of continued spontaneous reports of tardive dyskinesia in patients who used metoclopramide, the majority of whom had taken the drug for more than three months.

Consumers and health care professionals are encouraged to report adverse events to the FDA's MedWatch program at 800-FDA-1088, by mail at MedWatch, HF-2, FDA, 5600 Fishers Lane, Rockville, Md. 20852-9787, or online at: www.fda.gov/medwatch/report.htm

Elite Announces Drug Application Filing For Synthetic Narcotic Analgesic Accepted by FDA

Globes News Wire Source

Elite Pharmaceuticals, Inc. ("Elite" or the "Company") (AMEX:ELI) in collaboration with ThePharmaNetwork, LLC., announced today the acceptance by the U.S. Food and Drug Administration (FDA) of the Abbreviated New Drug Application (ANDA) for a generic equivalent of a synthetic narcotic analgesic drug product. The product had annual sales of approximately $36 million in 2007. Elite will manufacture the product and will receive a share of the profits from the sale of the product upon commercialization.

"We are pleased to reach this milestone and look forward to working with ThePharmaNetwork in this venture," commented Bernard Berk, Chairman and CEO for Elite. "With the revenue generated from the Lodrane(r) products along with the proceeds of our recent capital raise, Elite continues to move forward with the development of our two lead pain products, ELI-216, our abuse resistant oxycodone, and ELI-154, our once daily oxycodone product and will complete the work necessary for initiating Phase III clinical studies. Prescription drug abuse is a national crisis and abuse resistant drugs, like those being developed by Elite, are aimed at making a significant impact on this problem. ELI-216 is differentiated from other abuse resistant products in development by being the only once daily oxycodone using a pharmacological approach for abuse resistance. The pharmacological approach, we believe, compared to other technologies can provide a higher barrier for those recreational drug users trying to use these prescription drugs inappropriately to achieve a euphoric high and the once daily delivery provides a more consistent blood levels of the drug for these chronic indications as compared to the current sustained release oxycodone products. Elite will continue to prosecute the patents it has filed for this product and is preparing to file additional patents to strengthen our intellectual patent estate. Elite has also improved its financial condition by restructuring its workforce which, together with the growth in Elite's Lodrane revenues (approximately $1.3 million in last 6 months), is expected to significantly reduce Elite's operating losses. Lodrane 24(r) and Lodrane 24D(r) are products manufactured by Elite and sold and distributed by our partner ECR Pharmaceuticals. We will continue to seek out additional partnering prospects and other venture opportunities to leverage our proprietary opioid abuse technology and our unique drug delivery systems."

U.S. Food & Drug Administration Approved the use of REYATAZ® (atazanavir sulfate) Boosted with Ritonavir, in Combination Therapy, for Previously Untreated HIV-1 Infected Adult Patients

Business Wire Source

Bristol-Myers Squibb Company (NYSE: BMY) announced today that the U.S. Food & Drug Administration (FDA) approved the use of REYATAZ® (atazanavir sulfate) 300 mg once-daily boosted with ritonavir 100 mg as part of combination therapy in previously untreated (treatment-naive) HIV-1 infected patients. REYATAZ boosted with ritonavir (REYATAZ/r) taken once daily with food is recognized by the U.S. Department of Health and Human Services (DHHS) as a preferred component of combination HIV therapy for treatment-naive patients1.

For treatment-naive patients who are unable to tolerate ritonavir, REYATAZ 400 mg (without ritonavir), taken once daily with food, is recommended.

This use of once-daily REYATAZ/r in HIV-1 infected treatment-naive adult patients is based on 48-week results from the CASTLE study, which demonstrated similar antiviral efficacy of REYATAZ/r to twice-daily lopinavir/ritonavir (lopinavir/r), each as part of HIV combination therapy, in treatment-naive HIV-1 infected adult patients.

Within the CASTLE study, the REYATAZ/r arm was associated with low increases from baseline in total cholesterol (13 percent), LDL cholesterol (14 percent), HDL cholesterol (29 percent), and triglycerides (15 percent). The lopinavir arm was associated with 25 percent increase in total cholesterol, 19 percent increase in LDL cholesterol, 37 percent increase in HDL cholesterol, and 52 percent increase in triglycerides. Two percent of patients in the REYATAZ® (atazanavir sulfate)arm and eight percent of patients in the lopinavir arm required lipid-lowering therapy in the study, compared to 1 percent in each arm at baseline.

Safety events in this study were consistent with prior experience. Grade 2-4 treatment-related adverse events that occurred in two percent or greater of patients in the CASTLE study included jaundice (4 percent and zero percent), nausea (4 percent and 8 percent), diarrhea (2 percent and 11 percent) and rash (3 percent and 2 percent) in the REYATAZ/r and lopinavir/r arms, respectively. Grade 3–4 increases in total bilirubin were seen in 34 percent of patients in the REYATAZ/r arm and in less than 1 percent of patients in the lopinavir/r arm.

"Bristol-Myers Squibb is committed to developing medicines that enhance the care of people living with HIV and AIDS," said Elliott Sigal, M.D., Ph.D., Executive Vice President, Chief Scientific Officer and President, Research and Development, Bristol-Myers Squibb. "Boosted REYATAZ provides health care professionals a newly approved, once-daily dosing option as part of combination therapy for patients naive to HIV therapy."

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.

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.

Effectiveness Summary Preparation Detailed in Guidance

FDA News Source

The integrated summary of effectiveness (ISE) required in NDAs and encouraged in BLAs should include a detailed analysis of study results rather than just a summary of individual trials, according to an FDA draft guidance.

FDA Wants More Information on J&J Antibiotic

FDA News Source

Johnson & Johnson (JNJ) received a complete response letter from the FDA requesting additional information before it approves the company's antibiotic Doribax as a treatment for hospital-acquired pneumonia, including the ventilator-related form of the disease.

Doribax (doripenem), which is in the carbapenem class of antibiotics, is approved in the U.S. for the treatment of complicated intra-abdominal infections and complicated urinary tract infections.

J&J is reviewing the letter and will work to resolve questions from the FDA, the company says in a written statement. Although the firm would not say whether it would have to conduct an additional clinical trial to secure approval, the outcome of an advisory committee meeting on the product earlier this year indicated new clinical data would be necessary.

In July, the FDA's Anti-Infective Drugs Advisory Committee voted 8-5 that the product was safe and 7-6 that it was effective. However, the committee voted 9-4 that there was not sufficient scientific justification for the design of noninferiority clinical trials J&J used to support approval of the indication. The design included a noninferiority margin of 20 percent, and the FDA said it needed to be roughly 10 percent.

During the meeting, committee member Thomas Fleming, professor of biostatistics at the University of Washington, said J&J might need to use other endpoints or conduct a superiority trial.

BioDelivery Sciences Anticipates First Half 2009 Approval of BEMA Fentanyl (ONSOLIS)

Business Wire Source

BioDelivery Sciences International, Inc. (Nasdaq:BDSI) today announced receipt of a Complete Response letter from the U.S. Food and Drug Administration (FDA) regarding the Company’s New Drug Application (NDA) for BEMA™ Fentanyl, which will be marketed in the United States as ONSOLIS (fentanyl buccal soluble film). The FDA has requested that the Company make modifications to the submitted risk management program. All aspects of the review were complete and no deficiencies were noted in chemistry, manufacturing and controls, nonclinical, or clinical efficacy/safety. The Company will submit the requested information and anticipates a first half 2009 approval.

The FDA requested conversion of the risk minimization action plan (RiskMAP) submitted as part of the NDA for ONSOLIS into a Risk Evaluation and Mitigation Strategy (REMS). REMS is a new term for a strategy and plan aimed at ensuring the benefits of a drug outweigh its risks. The REMS requested of BDSI is believed to be the result of the FDA's recent experience with other high-potency opioid products and the new authority granted under the Food and Drug Administration Amendment Act (FDAAA) enacted in March of 2008. This followed BDSI’s submission of its ONSOLIS NDA in October 2007.

"We are pleased with this significant and extremely positive development for our Company,” stated Dr. Mark A. Sirgo, President and Chief Executive Officer of BDSI. “We have been anticipating the REMS request and have been proactively evaluating a series of options that will enable us to mitigate any delay in approval. All other aspects of our ONSOLIS NDA were reviewed positively and with no deficiencies noted. I want to congratulate the entire team at BDSI for this tremendous accomplishment."

Dr. Sirgo continued, "We believe that FDA approval of ONSOLIS and its U.S. commercial launch should add considerable value to BDSI based on the aggregate $30 million in approval and launch milestone payments, sales-based milestone payments, and double-digit royalty on sales, which provide the means to accelerate development of our pipeline. In addition, the outcome of the ONSOLIS NDA review validates the BEMA drug delivery platform and should immediately enhance the value of other BEMA products in development, particularly BEMA Buprenorphine, our second pain product. We believe that the future of BDSI continues to be very promising."

According to Dr. Andrew Finn, Executive Vice President, Product Development, "We have been working over the last several months with Meda AB, our partner for the commercialization of ONSOLIS, to prepare for a potential REMS requirement. These activities have put us in a position to respond rapidly to FDA’s request. Depending on FDA review time, approval could occur as early as the first quarter or as late as 2Q09."

"With respect to our financial position, we have managed our cash prudently over the course of 2008 and have a few months of cash in reserve," said Dr. Sirgo. "We have a financial plan that includes several choices to bridge the gap to approval and the receipt of milestone payments from Meda totaling $30 million. Importantly, we will seek to only raise the capital required to reach the anticipated approval, with little or no dilution to our stockholders. It should be noted that the costs associated with finalization and implementation of the REMS for ONSOLIS™ will be the responsibility of Meda."

BDSI’s lead product under development is ONSOLIS (fentanyl buccal soluble film) a potential treatment for "breakthrough" pain (i.e., episodes of severe pain which "break through" the medication used to control the persistent pain) in opioid tolerant patients with cancer. ONSOLIS consists of a small, dissolvable, polymer film, formulated with the opioid narcotic fentanyl for application to the buccal mucosa (inner lining of the cheek). Fentanyl belongs to the group of medicines called narcotic analgesics, which are used to relieve pain. The BEMA delivery technology is particularly well suited for the delivery of products where rapid onset of activity and convenient administration are important. BDSI believes there is a clear need and growing market for additional narcotic agents in alternative dosage forms to provide rapid and convenient pain relief.

BDSI is a specialty pharmaceutical company that is focused on developing innovative products to address growing market opportunities, including conditions such as pain. The company utilizes its owned and licensed patented drug delivery technologies to develop, partner, and commercialize new products using proven therapeutics. BDSI’s pain franchise currently consists of two products in development utilizing the company's patented BEMA oral adhesive film technology: ONSOLIS, a potential treatment for "breakthrough" pain in opioid tolerant patients with cancer, and BEMA Buprenorphine, a second analgesic with at least one potential target indication for the treatment of moderate to severe pain. The company is working with its BEMA technology and its patented Bioral cochleate technology on products targeted at conditions common to oncology and surgical patients such as pain and infections. The company headquarters is located in Raleigh, North Carolina, and its principal laboratory is located in Newark, New Jersey. For more information please visit www.bdsinternational.com.

Heparin Contamination Has Wide Scope

Philadelphia Injury Board Source

Contamination of the blood thinner heparin was discovered earlier this year. One of the largest US suppliers of heparin is Baxter International, and Baxter recalled most of its heparin in February 2008 after patient deaths were linked to the product. Accorinding to the FDA, US deaths linked to contaminated heparin has increased to 81, up from the earlier count of 62. Twelve companies in China are the sources of the contaminated raw product that was part of the heparin linked to deaths. According to Chinese officials, even though the contaminated product came from China, they do not believe that the contamination caused the deaths. The contaminated product affected several countries, including France, Germany, Canada, Italy, and the US. According to the FDA, the contaminated product entered the global market in 2007. Testing has found contaminated heparin in IV drug products and some diagnostic tests. It is still unclear how the contaminated raw product became mixed with heparin.

Cytokinetics Announces Completion of Interim Safety Analysis in Ongoing Phase IIa Clinical Trial of CK-1827452

Market Wire Source

Cytokinetics, Incorporated (NASDAQ: CYTK) announced the completion of a protocol-defined interim analysis in an ongoing Phase IIa clinical trial evaluating the safety of CK-1827452 in patients with ischemic cardiomyopathy and angina. Based on the Safety Review Committee's review of safety data from the first cohort of patients, the Committee has recommended that the company open the second cohort of this clinical trial for enrollment. To date, no serious adverse events have been reported in this ongoing clinical trial. Cytokinetics also reiterated that it expects to conclude this trial by the end of 2008. CK-1827452, a novel cardiac myosin activator, is being developed for the potential treatment of patients with either acutely decompensated or chronic heart failure. CK-1827452 is the subject of a collaboration and option agreement between Cytokinetics and Amgen Inc.

"Based on our careful review of safety data from this trial, I am comfortable recommending that the trial proceed to enroll patients in the second cohort, in which patients randomized to treatment with active CK-1827452 will receive a higher dose than in Cohort 1," stated Barry H. Greenberg, M.D., Chair of the Safety Review Committee for this clinical trial and Director, Advanced Heart Failure Treatment Program, University of California, San Diego Medical Center.

The company announced that 46 patients were enrolled and completed treatment in the first cohort of this trial and that, as per protocol, safety data from the first 31 of these patients were presented to the committee. No serious adverse events were reported for any patients in the first cohort and analyses of safety data from patients included in the interim analysis revealed no additional safety concerns.

"We look forward to sharing these data with the medical community at an appropriate scientific and medical forum and are now pleased to proceed forward with the next stage of this clinical trial," stated Andrew A. Wolff, M.D., F.A.C.C., Cytokinetics' Senior Vice President of Clinical Research and Development and Chief Medical Officer. "We believe these data, and data reported recently from other clinical trials, support the advancement of CK-1827452 in continuing trials."

In June 2008, at the Heart Failure Congress, the annual meeting of the Heart Failure Association of the European Society of Cardiology in Milan, Italy, Cytokinetics announced results from an interim analysis of its first and ongoing Phase IIa clinical trial of CK-1827452 in patients with stable heart failure. At the time of the analysis, 22 patients had been evaluated in this clinical trial. The safety data from this analysis suggested that CK-1827452 was well-tolerated with no serious adverse events reported in heart failure patients exposed to the intended range of doses and plasma concentrations. A pharmacodynamic-pharmacokinetic analysis of data from these 22 patients showed that when compared to placebo, CK-1827452 produced statistically significant and clinically relevant increases in Doppler-derived stroke volume and fractional shortening as a consequence of statistically significant prolongations of systolic ejection time. In this interim analysis, statistically significant correlations were observed between the increases in the three indices of cardiac ventricular function and increases in the plasma concentration of CK-1827452. Doppler-derived systolic ejection time and stroke volume measured during the second hour of infusion were the most sensitive indicators of effect. Changes in left ventricular ejection fraction, a measurement with high variability in patients with ventricular disease, did not reach statistical significance in that dataset. Across the range of plasma concentrations evaluated, the pharmacokinetics of CK-1827452 were generally linear with respect to dose and similar to those observed in the healthy volunteers in the first-time-in-humans Phase I trial of CK-1827452. Heart rate declined slightly at higher concentrations and there were no dose-related changes in blood pressure in this interim analysis. Cytokinetics plans to present additional data from these same 22 patients at the European Society of Cardiology 2008 Congress in Munich, Germany and also plans to present interim data including additional patients who have completed treatment in this ongoing trial in as part of the Late Breaking Clinical Trials Session at the Annual Meeting of the Heart Failure Society of America in Toronto, Ontario, Canada.

In addition to these two ongoing Phase IIa clinical trials, in April 2008, Cytokinetics opened enrollment in an open-label, non-randomized Phase IIa clinical trial designed to evaluate an intravenous formulation of CK-1827452 administered to patients with stable heart failure undergoing clinically indicated coronary angiography in a cardiac catheterization laboratory. Cytokinetics has conducted five Phase I clinical trials of CK-1827452 in healthy subjects: a first-time-in-humans study evaluating an intravenous formulation, an oral bioavailability study evaluating both intravenous and oral formulations, and three studies of oral formulations: a drug-drug interaction study, a dose proportionality study and a study evaluating modified-release formulations. Data from each of these trials have been reported previously.

Cytokinetics is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule drugs that may address areas of significant unmet clinical needs. Cytokinetics' cardiovascular disease program is focused to cardiac myosin, a motor protein essential to cardiac muscle contraction. Cytokinetics' lead compound from this program, CK-1827452, a novel small molecule cardiac myosin activator, entered Phase II clinical trials for the treatment of heart failure in 2007. Under a strategic alliance established in 2006, Cytokinetics and Amgen Inc. are performing joint research focused on identifying and characterizing activators of cardiac myosin as back-up and follow-on potential drug candidates to CK-1827452. Amgen has obtained an option for an exclusive license to develop and commercialize CK-1827452, subject to Cytokinetics' development and commercial participation rights. Cytokinetics' cancer program is focused on mitotic kinesins, a family of motor proteins essential to cell division. Under a strategic alliance established in 2001, Cytokinetics and GlaxoSmithKline (GSK) are conducting research and development activities focused on the potential treatment of cancer. Cytokinetics is developing two novel drug candidates that have arisen from this program, ispinesib and SB-743921, each a novel inhibitor of kinesin spindle protein (KSP), a mitotic kinesin. Cytokinetics is sponsoring a Phase I/II clinical trial of ispinesib as monotherapy as a first-line treatment in chemotherapy-naïve patients with locally advanced or metastatic breast cancer. In addition, Cytokinetics is conducting a Phase I/II trial of SB-743921 in patients with non-Hodgkin or Hodgkin lymphomas. GSK has obtained an option for the joint development and commercialization of ispinesib and SB-743921. Cytokinetics and GSK are conducting collaborative research activities directed to the mitotic kinesin centromere-associated protein E (CENP-E). GSK-923295, a CENP-E inhibitor, is being developed under the strategic alliance by GSK; GSK began a Phase I clinical trial with GSK-923295 in 2007. In April 2008, Cytokinetics announced the selection of a potential drug candidate directed towards skeletal muscle contractility which may be developed as a potential treatment for skeletal muscle weakness associated with neuromuscular diseases or other conditions. All of these drug candidates and potential drug candidates have arisen from Cytokinetics' research activities and are directed towards the cytoskeleton. The cytoskeleton is a complex biological infrastructure that plays a fundamental role within every human cell. Additional information about Cytokinetics can be obtained at www.cytokinetics.com.

Cell Genesys Halts VITAL-2 GVAX Trial in Advanced Prostate Cancer

Business Wire Source

Cell Genesys, Inc. (Nasdaq:CEGE) today announced that it has terminated VITAL-2, the second of two Phase 3 clinical trials of GVAX immunotherapy for prostate cancer, which compares GVAX immunotherapy in combination with Taxotere® (docetaxel) to Taxotere plus prednisone in patients with advanced-stage prostate cancer. The Company ended the trial as recommended by its Independent Data Monitoring Committee (IDMC) which, in a routine safety review meeting held this week, observed an imbalance in deaths between the two treatment arms of the study. To date, VITAL-2 enrolled 408 patients. The IDMC based its recommendation on 114 deaths of which 67 occurred in the GVAX plus Taxotere combination treatment arm and 47 deaths occurred in the Taxotere control arm. At this time, a specific cause for the imbalance in deaths has not been identified and the IDMC reported no new safety issues for GVAX when administered in combination with Taxotere. The Company plans to fully analyze the clinical data from these patients to attempt to understand the potential cause for the higher rate of deaths observed in the GVAX immunotherapy plus Taxotere combination arm, including an assessment of potential imbalances between the two arms of the study such as baseline characteristics and prognostic factors, as well as other treatment variables. In light of the IDMC’s observation with respect to VITAL-2, the Company has requested that the IDMC perform a previously unspecified futility analysis of VITAL-1, the other Phase 3 clinical trial of GVAX immunotherapy for prostate cancer. The Company expects the results of the VITAL-1 futility analysis in approximately one month.

GVAX immunotherapy for prostate cancer is comprised of two prostate tumor cell lines that have been modified to secrete GM-CSF (granulocyte-macrophage colony-stimulating factor), an immune stimulatory cytokine that plays a key role in stimulating the body's immune response, and then irradiated for safety. GVAX immunotherapy for prostate cancer is designed to be administered through intradermal injections on an outpatient basis.

Cell Genesys (Nasdaq: CEGE) is focused on the development and commercialization of novel biological therapies for patients with cancer. The company's lead product platform is GVAX® immunotherapy for cancer, which holds the potential to treat multiple types of cancer including prostate cancer, leukemia, pancreatic cancer and lung cancer. Cell Genesys continues to hold an equity interest in its former subsidiary, Ceregene, Inc., which is developing gene therapies for neurodegenerative disorders. Cell Genesys is headquartered in South San Francisco, California, and has manufacturing operations in Hayward, California. For additional information, please visit the company’s website at www.cellgenesys.com.

According to Cutting Edge Information Research, Patient Recruitment Costs Having Greater Impact on Clinical Development

Market Wire Source

The difficulty of recruiting suitable patients for clinical trials has been a greater factor in rising trial costs, according survey data collected from pharmaceutical companies. A new study by pharmaceutical business intelligence leader Cutting Edge Information, "Streamlining Clinical Trials," finds that on a cost-impact scale of 1-5, patient recruitment received a mark of 4.1, a 6% increase from a similar study conducted in 2006.

The report explores reasons behind the growing challenge of patient recruitment and retention, such as more stringent FDA regulations, budgetary constraints, and timeline overrun. Another challenge that impacts recruitment is overlap of patients for various studies at a single site. The sample populations in this case are lowered, making it difficult to find the necessary candidates to conduct trials. This challenge results in cost increase.

David Richardson, project leader of the study said, "Companies are continuing to encounter development challenges, and increased patient recruitment costs make it more difficult to run a trial smoothly."

A complementary brochure is available for download at http://cuttingedgeinfo.com/clinicaltrialbenchmarking/index.htm#body.