Amgen Cuts 100 Jobs at Washington Manufacturing Plant

SEATTLE --An Amgen Inc. spokeswoman confirms that the drugmaker is cutting 100 jobs at its clinical drug manufacturing site in the Seattle suburb of Bothell, Wash.

Carol Pawlak says the cutbacks are not part of any larger companywide reductions. The biotechnology company has 17,000 employees worldwide.

Pawlak said Thursday the company is merging clinical drug trial work at its Bothell facility with operations at its company headquarters in Thousand Oaks, Calif.

She says laid-off employees can reapply for other positions within the company.

Xconomy, a business and technology news site that reported the job cuts, says the cutbacks leave about 70 employees in Bothell, and nearly 900 in Washington state. Pawlak confirms those figures

Scar-Reducing Drug Shows Promise

A drug designed to reduce scarring after surgery or injury has shown promising results in early human trials, UK researchers say.

Study links the Pill to increased lupus risk

It found women taking birth control pills, especially those who have just started taking them, may be 2 1/2 times more likely to contract the autoimmune disease.

The link between the two has been debated for some time. This new study in Arthritis Care and Research adds weight to earlier studies that have shown a connection.

Researchers speculate that estrogen from oral contraceptives could be responsible for the increased risk. Estrogen can affect the body's immune response which could then trigger a genetic predisposition to the disease. They add that the newer oral contraceptives are substantially less likely to increase the risk of lupus. But other experts say the risk is quite small.

Pharmaceuticals Provide a Takeover Tonic

Merger and acquisition activity has slowed dramatically as the global financial crisis restricts the ability of companies to put together debt-financed deals.
FT.com

FDA Rebuffs Teva’s Citizen Petition on Generic Copaxone Filings

The FDA has declined to review a citizen petition submitted by Teva Neurosciences asking the agency not to accept applications for generic versions of the Copaxone multiple sclerosis treatment until certain conditions are met. The agency told Teva that it would be “premature and inappropriate” to review the Copaxone (glatiramer acetate) petition filed last September. In addition, the FDA didn’t address or take action on Teva’s requests in the petition, the company says in a statement.
Generic Line

Supreme Court Asked to Review Prescriber Data Case

IMS Health and SDI Health have asked the U.S. Supreme Court to review lower court decisions on whether states may prohibit data mining — the collection and publication of prescribing trends, which drugmakers use to identify physicians who treat particular conditions for marketing purposes. Many doctors object to the tracking of their history of dispensing prescriptions. Drug companies use that information to discuss the medical benefits of products with physicians. The same data can be used by drugmakers to track the competition.

FDA Reverses Course, Drugmakers Allowed to Make Morphine Solution

Patient and hospice groups’ concerns have prompted the FDA to reverse its decision that manufacturers of morphine sulfate 20-mg/mL oral solution must stop producing the pain drug. The FDA sent nine warning letters telling companies to halt production of unapproved versions of morphine, hydromorphone and oxycodone products. The FDA is now amending those letters to allow companies to make the 20-mg/mL oral solution to meet the needs of hospice patients with severe pain, CDER Deputy Director Douglas Throckmorton said.

Medtronic Wraps Up Buy of CoreValve

US medical device company Medtronic said it has closed the acquisition of local company CoreValve, which develops products that provide an alternative to heart valve replacement surgery.

Panel Rejects Stryker OP-1 Bone Putty for PMA Approval

An FDA advisory committee voted 6–1 last week against recommending premarket approval (PMA) of Stryker Biotech’s OP-1 putty for use in an expanded patient population. The Orthopedic and Rehabilitation Devices Advisory Committee cited lingering concerns of whether the device promoted bone growth and pointed to safety issues regarding immunogenicity and maternal and fetal antibody transfer.

Minimally Invasive Technologies Expected to Be Boom Market

With the market for minimally invasive devices expected to boom over the next several years, industry is pushing government regulators to study the technology, and analysts recommend that devicemakers develop products for this market. “Over the next decade, it’s expected that all surgeries will be minimally invasive,” Lazard Capital Markets analyst Sean Lavin said. “Virtually all device companies are working toward developing products that are less invasive. … If you’re not doing something minimally invasive, you’re probably not doing business.”

Crofelemer, First-in-Class Anti-Diarrheal Agent, Positive Clinical Results to be Discussed at 13th Annual US-Japan CMSP in Kolkata, India

OUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Napo Pharmaceuticals, Inc., (“Napo”) announces that oral presentations regarding the safety, efficacy and mechanism of action of crofelemer in clinical trials in severe acute dehydrating watery diarrhea and cholera, as well as the preclinical results for other small molecule cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel blockers, will be presented at the upcoming U.S. - Japan CMSP: 13th International Conference on Emerging Infectious Diseases (EID) in the Pacific Rim – Focused on Enteric Diseases, April 6-9 in Kolkata, India. Data will also be presented on other pre-clinical anti-secretory agents. Glenmark Pharmaceuticals Limited (“Glenmark”) is currently undertaking clinical trials on crofelemer in India and anticipates introduction in the country in 2010. Glenmark has both developmental and marketing rights for the molecule in 140 countries around the world including India.

Pradip K. Bardhan of the International Center for Diarrheal Disease Research (“ICDDR”) in Bangladesh will be summarizing the results from two clinical studies that evaluated the safety and efficacy of Napo’s novel anti-secretory anti-diarrheal agent, crofelemer (NP-303), in the treatment of adult acute infectious diarrhea (conducted in India by Glenmark) and cholera (conducted at the ICCDR in Bangladesh). The study of the effects of crofelemer in adult infectious diarrhea, predominantly from enterotoxigenic Escherichia coli (ETEC) infection, was conducted without the use of any antibiotics, while the study in adult patients suffering from cholera infection was conducted in combination with a single oral dose of azithromycin. These results collectively show that crofelemer represents a first-in-class treatment option as an antisecretory agent for the treatment of acute dehydrating watery diarrhea, with or without the use of antibiotics.

Perhaps the most important application of crofelemer is to address the devastating morbidity and mortality of ~2.5 million children under 5 who die each year primarily in developing countries, from the devastation of diarrhea and dehydration of cholera and watery diarrhea due to multiple etiologies and the global crisis in access to clean water. Cholera, for example, results in death for >50% of its victims without adequate rehydration. Current standard-of-care therapy focuses on rehydration therapy and antibiotic therapy to target the infectious agent. There are no current therapies for cholera which decrease the secretion of fluid into the small intestine. Patients are at maximum risk during the first 6-18 hours. Crofelemer demonstrated significant reduction (approximately 32%) in stool volume output in the first 6 hours, a trend which continued through the first 24 hours of observation — the period of time where patients are often in a life-threatening situation due to severe dehydration. In the severe acute watery diarrhea study, overall clinical success was achieved in about 75% of the crofelemer group, including statistically significant results on all seven measurements of diarrhea symptoms. Both these studies was conducted in adults.

A separate presentation will be given by Dr. Alan S. Verkman of the Departments of Medicine and Physiology at the University of California, San Francisco, California, discussing the mechanism of action of crofelemer as a first-in-class, small molecule dual inhibitor of CFTR chloride channel and calcium activated chloride channel (“CaCC”). Furthermore, this presentation will provide some of the preclinical results with other novel small molecule inhibitors of CFTR (“second gen CFTR”), which have been exclusively licensed by Napo from the University of California regents.

(See Abstracts below)

Lisa A. Conte, CEO of Napo Pharmaceuticals, Inc. commented: "Napo is thrilled that the important results of the trials of crofelemer for cholera and for severe adult acute infectious diarrhea are being presented in such a forum and I would like to thank Glenmark, Dr. Bardhan and the ICDDR for their contributions. We look forward to Glenmark’s anticipated introduction of crofelemer in India in 2010 and in other countries thereafter. Napo is committed to the development of crofelemer for pediatric populations and collaboration with both crofelemer and second gen CFTR to address the global impact of diarrhea diseases.”

Napo’s commercial licensee for crofelemer in the United States, Salix Pharmaceuticals, Inc., expects to file an NDA for the indication of chronic diarrhea in people living with HIV/AIDS in the first half of 2010. Crofelemer is in the final Phase 3 study for this indication and has been fast-tracked by the FDA.

J&J Cutting About 900 Jobs From Pharma Unit

NEW YORK-Diversified health care products company Johnson & Johnson said Thursday it will cut about 900 jobs, mainly from its Ortho-McNeil-Janssen Pharmaceuticals unit.

The cuts include a mix of attrition and hiring freezes. They are part of the company's strategy to trim its U.S. sales force and refocus its approach in the market, according to Kara Russell, spokeswoman for the Ortho-McNeil-Janssen Pharmaceuticals unit.

The cuts amount to about 6 percent of J&J's overall pharmaceutical sales force.

In January, the maker of baby shampoo, contraceptives and other health items forecast weaker results in 2009, blaming the global recession, unfavorable currency exchange rates and intensified pressure from both generic drugs and competitors' new products.

Pfizer's Oncology Business Unit Appoints Vice President of Medical Affairs

EW YORK--(BUSINESS WIRE)--Apr 10, 2009 -

Pfizer Inc announced today the appointment of Martine J. George, M.D., M.Sc, to Vice President of Medical Affairs for its Oncology Business Unit. Dr. George will be responsible for managing external relationships with cancer agencies, organizations and specialists around the world.

“We are delighted that Dr. George – with her impressive record as a leader in global pharmaceutical organizations – will be joining Pfizer's Oncology Business Unit and look forward to her contributions in advancing science needed to bring innovative medicines to patients,” said Mace L. Rothenberg, M.D., senior vice president, Clinical Development and Medical Affairs for the Oncology Business Unit.

Dr. George possesses 20 years of experience in leading pharmaceutical organizations with expertise in medical affairs, clinical research and regulatory affairs. Most recently, she held the position of Senior Vice President of Drug Development and Chief Medical Officer atGPC Biotech, Inc. where she was responsible for the strategy and development activities for satraplatin and all early development compounds.

Her previous experience includes serving as Senior Vice President and Head of Oncology for Johnson & Johnson and as Vice President of Clinical Affairs at Ortho Biotech, Inc. Additionally, she has led the medical affairs group at Rhone-Poulenc Rorer (Sanofi-Aventis), worldwide clinical research and regulatory affairs at Gencell, and clinical research and development at Sandoz Pharmaceuticals Corporation (Novartis). Prior to joining industry she held an academic position at Institute Gustave Roussy, Villejuif, France for several years.

Dr. George received her M.Sc in Pharmacology from Montreal University in 1973, her M.D. from Paris University in 1975, and is board certified in Medical Oncology.

the Impact of the Withdrawal of Raptiva (efalizumab) on the Psoriasis Market

EXTON, Pa., April 10 On April 8th, 2009, Genentech and Roche announced the voluntary withdrawal of Raptiva (efalizumab, marketed by Genentech/Roche and Xoma) from the US market. The withdrawal comes after recent post-marketing reports of PML associated with Raptiva treatment.

BioTrends will field its fourth annual TreatmentTrends(TM): Psoriasis survey on April 13th with a special section dedicated to the impact of the Raptiva withdrawal. The on-line survey will be completed by 150 clinical dermatologists and is structured to assess treatment prevalence and brand use for topical, oral, and biologic agents. A comprehensive attribute analysis is provided for each class to indicate areas of unmet need and market share projections for the next six months. In addition, awareness and interest in products in late stage development, such as Centocor's STELARA (ustekinumab) and Abbott's ABT-874 is assessed. The report will be published in early May.

A second report offered by BioTrends, ChartTrends(TM): Biologics in Psoriasis, is a report that is based on actual patient level audit data collected through a proprietary audit tool. In this report, 1000 patients who are currently being treated with biologic agents will be reviewed to analyze the treatment algorithm that culminates in the use of biologic agents, patient demographics/co-morbidities associated with specific biologic brand use, product switching incidence and rationale, and concomitant medications. A special section focused on switches from Raptiva will be included to understand if these patients migrate to other biologic brands or are discontinued altogether from biologic therapy. This report will be published in early June.

According to last year's TreatmentTrends(TM): Psoriasis report, market share for Raptiva had steadily declined since 2006 and only 44% of the dermatologists surveyed were using the product in their practices in April 2008. Amgen/Wyeth's Enbrel and Abbott's Humira, the most frequently prescribed biologics in psoriasis, were rated significantly higher than Raptiva on nearly all of the most important attributes. However, Raptiva held a competitive advantage over all biologic competitors on its efficacy in palmo-plantar psoriasis.

New drug shows promise in treating drug-resistant prostate cancer

A new therapy for metastatic prostate cancer has shown considerable promise in early clinical trials involving patients whose disease has become resistant to current drugs.

Chemists and biologists at UCLA and colleagues at several other institutions, including Memorial Sloan-Kettering Cancer Center, have created a new drug to treat a particularly lethal form of the disease, known as castration-resistant prostate cancer, or CRPC. Also referred to as hormone-refractory prostate cancer, CRPC is resistant to further treatment by anti-hormone drugs such as Casodex and Eulexin.

In an article published April 9 in the advanced online edition of the journal Science, the scientists describe the development and testing of two novel compounds, MDV3100 and RD162, which block the androgen receptor (AR) in CRPC cells, and report results from clinical trials in which MDV3100 was found to lower prostate-specific antigen (PSA) levels — a marker for tumor growth — in men with CRPC.

The new, small organic molecule MDV3100 was "designed as a very strong antagonist of the androgen receptor to stop the growth of any prostate cancer that requires the AR for propagation, which includes most forms of prostate cancer," said Michael Jung, UCLA professor of chemistry and biochemistry and a researcher at UCLA's Jonsson Comprehensive Cancer Center, whose research group synthesized both MDV3100 and RD162.

The biology research was carried out in the UCLA departments of medicine, urology and pharmacology by Charles Sawyers and his research group; Sawyers has since moved to Memorial Sloan-Kettering Cancer Center in New York, where he serves as chair of the human oncology and pathogenesis program. The UCLA patents for both compounds were licensed by the pharmaceutical company Medivation Inc., which chose to test MDV3100 in clinical trials.

The drug has successfully completed Phase 1 and Phase 2 clinical trials, and the Food and Drug Administration has agreed to allow Medivation to begin what Jung described as "the pivotal Phase 3 clinical trials."

The results of clinical studies with MDV3100 were described at the 2009 ASCO Genitourinary Cancer Symposium in February by the trials' principal investigator, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center. In general, the drug, at 240 mg once a day, was very effective at lowering PSA levels and also in reducing the number of circulating tumor cells, without any significant toxicity.

"I think it is quite likely that the exciting results seen in the smaller population will also be evident in the larger Phase 3 trial and that the drug could be approved for use in the next few years," said Jung, who is also a member of the California NanoSystems Institute (CNSI) at UCLA.

Of 30 men with anti-androgen–resistant prostate cancer who received low doses of MDV3100 in the multisite Phase 1/2 trial designed to evaluate safety, 22 showed a sustained decline in PSA levels, an indication that their cancer was responding favorably to the drug. This trial is still underway, and results from a total of 140 patients receiving higher doses of the drug will be reported within the next year, Sawyer said.

The Phase 3 clinical trial will evaluate the drug's effect on survival in a large group of patients with metastatic prostate cancer.

MDV3100 and RD162 are second-generation anti-androgen therapies that prevent male hormones from stimulating the growth of prostate cancer cells. These new compounds appear to work well even in prostate cells that have a heightened sensitivity to hormones; that heightened sensitivity makes prostate cancer cells resistant to existing anti-androgen therapies.

Approximately 186,000 new cases of prostate cancer are diagnosed each year in the United States. The male hormones testosterone and dihydrotestosterone, which are also known as androgens, spur the growth of prostate cells, and drugs that block the receptors for these hormones are the most common treatment for the disease in its advanced, metastatic stage. Anti-androgen drugs, such as bicalutamide (Casodex), suppress the growth of cancer cells temporarily, but in most patients, the cancer ultimately develops resistance to drugs. Approximately 29,000 men in the United States die each year from the disease.

Prostate cancer becomes resistant to anti-androgen drugs when cancer cells begin to increase production of the androgen receptor, Sawyers said. When the level of androgen receptors on the cells' surface reaches a certain level, the drugs that originally suppressed the cancer actually begin to stimulate cancer growth.

Because of this backlash effect, many scientists have questioned whether blocking the androgen receptor is a wise course of action. Sawyers and his colleagues, however, believe that blocking the receptor is critical to successful treatment. They set out to design a new generation of drugs that can block the androgen receptor without unwanted side effects, even when levels of the receptor are high.

Researchers in Jung's and Sawyers' laboratories based their designs on a drug that tightly attaches to the site on the androgen receptor that binds with testosterone. If that site is blocked, the hormone cannot bind to prostate cells and tell the receptor to stimulate growth. Using this initial drug as a chemical scaffold, the researchers synthesized nearly 200 slightly different versions of the drug. They tested each one in the laboratory on prostate cancer cells that had been engineered to produce high levels of androgen receptor.

This screening yielded MDV3100 and RD162, molecules which tightly bind to the androgen receptor and do not show the cancer-stimulating effect of bicalutamide and other current anti-androgen drugs. The molecules were good candidates for drugs, because they are readily absorbed into the blood when taken orally and they persist in the bloodstream. The researchers tested the new drugs' effectiveness in mice with tumors derived from drug-resistant prostate cancer cells.

"To our delight, we found that these compounds caused very dramatic shrinkage of tumors in the mice," Sawyers said. "While treating these animals with bicalutamide produced a modest effect on their tumors, the new drugs caused the tumors to shrink dramatically, and in some animals almost completely."

Sawyers said the new drugs bind tightly enough to the natural hormone-binding site on androgen receptors to prevent most of them from functioning, even in cells with many androgen receptors.

The promising laboratory studies led Medivation to license the drugs for commercial development.

Medivation has received permission from the FDA for a large Phase 3 clinical trial of MDV3100 on about 1,200 patients with anti-androgen-resistant disease. This study will assess MDV3100's effect on cancer survival and will take several years.

While the preliminary results are promising, Sawyers said his laboratory will continue to seek further improvements in drug therapy for prostate cancer.

"There were some men in the initial trial in which the drug didn't work at all, and we want to find out why," he said. "It may be because the drug is not potent enough to overcome resistance due to androgen receptor over-expression. Or it may be that the cancers in these men are not driven by the androgen receptor anymore. Also, there were men who initially received benefit from the drug but then relapsed, and their PSA levels came back up. We want to understand the mechanism of that relapse and to try to develop drugs that prevent that renewed resistance."

For years, no treatment was available for CRPC; recently paclitaxel — a strongly cytotoxic drug — was approved.

'Unapproved' morphine to stay on market, FDA rules

WASHINGTON (CNN) -- A form of liquid morphine used by terminally ill patients will remain on the market even though it is an "unapproved drug," according to a decision by the Food and Drug Administration.

After talking with hospital and hospice organizations, which expressed concern that taking the product off the market would result in hardship for terminally ill patients and their caregivers, the agency decided to extend the usage of morphine sulfate oral solution 20 mg/ml.

The agency wants to ensure there is shortage of the drug while patients wait for an approved product to take its place.

"While the FDA remains committed to ultimately ensuring that all prescription drugs on the market are FDA approved, we have to balance that goal with flexibility and compassion for patients who have a few alternatives for the alleviation of their pain," Dr. Douglas Throckmorton, deputy director of the FDA's Center for drug Evaluation and Research, said Thursday.

"In light of the concerns raised by these patients and their health-care providers, we have adjusted our actions with regard to these particular products."

Last month, the FDA sent warning letters to nine companies telling them to stop manufacturing 14 unapproved narcotics that are widely used to treat pain.

Seven of those companies made or distributed the oral morphine.

The morphine elixir is widely used by terminal patients in hospital and home hospice care settings and is manufactured by Lehigh Valley Technologies Inc., Mallinckrodt Inc. Pharmaceuticals Group, Boehringer Ingelheim Roxane Inc. and Cody Laboratories, Inc.

In its warning letter last month, the agency gave the companies 60 days to stop manufacturing the drug before enforcement action was taken.

Thursday's announcement did not prompt immediate reactions from the companies. A spokesman for Cody Laboratories said the firm did not have all the details of the decision. Other companies did not immediately return calls from CNN.

The FDA estimates there are several thousand drugs, mostly older products, marketed illegally without FDA approval in this country. Once an illegally marketed drug is identified, enforcement action begins because the agency does not have information on the quality of these drugs and has not had an opportunity to approve their labeling. In 1976 the agency began a program to bring companies manufacturing these drugs into compliance.

Thursday's announcement applies only to the morphine sulfate elixir 20mg/ml, and the warning letters sent to the other product manufacturers are still in effect.

Currently there are no approved morphine sulfate oral solution 20mg/ml products on the market. Until there are, the FDA says it will allow companies making and distributing the unapproved drugs to continue, until 180 days after any company receives approval to manufacture a new morphine replacement drug of the same dosage.

The FDA says it expects all companies marketing unapproved drugs to submit the necessary applications to get approval for those drugs

Test quickly assesses whether Alzheimer's drugs are hitting their target

A test developed by physician-scientists at Washington University School of Medicine in St. Louis may help assess more quickly the ability of Alzheimer's drugs to affect one of the possible underlying causes of Alzheimer's disease in humans, accelerating the development of new treatments.

Scientists used the test to show that an Alzheimer's drug given to healthy volunteers reduced production of a substance known as amyloid beta (A-beta), a normal byproduct of human metabolism that builds to unhealthy levels forming brain plaques in Alzheimer's patients. The drug candidate, LY450139, which is also known as semagacestat, is being studied in clinical trials by Eli Lilly and Company.

Ongoing clinical trials are studying the effect that semagacestat may have on cognitive function and biochemical and brain imaging biomarkers in patients with Alzheimer's disease. Washington University researchers wanted to see whether the new measurement technique, stable isotope-linked kinetics (SILK), could detect the study drug's impact on A-beta synthesis in healthy volunteers.

"Bringing an Alzheimer's disease drug into clinical trials from tests in animal models has always been challenging," says study director Randall Bateman, M.D., a Washington University neurologist who treats patients at Barnes-Jewish Hospital. "We haven't had a way to quickly and accurately assess a drug's effects, and that meant there always had to be some degree of educated guesswork when it came to setting the optimal dosage for humans. SILK may help to eliminate much of that guesswork."

The results appear online in Annals of Neurology on April 10.

Scientists are unsure whether increased A-beta production, reduced clearance or a combination of the two lead to the A-beta buildup in the brain, a process that many believe triggers Alzheimer's disease. Bateman and his colleagues are currently using SILK to try to answer this question.

Until SILK, there has not been a way to directly measure the production or clearance of A-beta. The efficacy of potential new Alzheimer's drug candidates has been assessed by monitoring the cognitive functions of patients with the disease for extended periods of time, which require large, lengthy and expensive studies.

In their double-blind study, scientists gave 20 healthy volunteers varying doses of either a study drug or a placebo. At the start of the SILK test, volunteers were connected to an intravenous drip that gave them a slightly altered form of the amino acid leucine, which is a component of A-beta.

Over the course of several hours, cells in the brain picked up the labeled leucine and incorporated it into the new copies made of A-beta and other proteins. The scientists took periodic samples of the subjects' cerebrospinal fluid to determine how much of the A-beta included altered leucine.

Tracking the rise of the percentage of labeled A-beta over time reveals the A-beta production rate. Scientists then stop the leucine labeling but continue analyzing spinal fluid samples. As the body removed old A-beta and made new A-beta, the percentage of A-beta containing altered leucine dropped, revealing the A-beta clearance rate.

The results suggest a dose-dependent drop in A-beta production, with an 84 percent reduction in A-beta production being measured with the highest study drug dose.

The SILK procedure takes 36 hours, but provides scientists a more detailed assessment of amyloid beta production and clearance levels than they can obtain through conventional methods.

"You could use a spinal tap to look directly at the amount of A-beta present in the cerebrospinal fluid, but we've shown that natural processes cause A-beta levels to change dynamically," says Bateman. "Such changes make it more difficult to assess the effects of a drug in that fashion."