Amgen's new osteoporosis drug cuts fracture risk

Thursday is a big day for Amgen Inc., as company officials meet with a Food and Drug Administration advisory panel in Washington to discuss their licensing application for a new drug that’s critical to the company’s future success.

So it came as welcome news when the Thousand Oaks-based drug manufacturer saw positive findings published Tuesday in the New England Journal of Medicine.

The studies, paid for by Amgen, found that the company’s osteoporosis drug denosumab considerably reduces fractures, findings that might buttress Amgen’s application.

Amgen Chief Medical Officer Sean Harper said they are pleased with the results.

“We really are excited about the opportunity to review our data and hear the discussion of the panel,” he said. “These are always big events and it’s exciting for everybody, but we’re certainly looking forward to it.”

Panel to look at drug

The Reproductive Health Drugs Advisory Committee will review Amgen’s application for FDA approval to use denosumab to treat osteoporosis in post-menopausal women and to prevent and treat bone loss in cancer patients undergoing hormone therapy.

The FDA uses such committees to get independent expert advice, though it does not have to follow a committee’s recommendation.

The FDA could make an approval decision in October. Most analysts think Amgen’s drug has a good chance of approval, with analysts at Morningstar giving it a 70 percent chance to get approval for those two indications on schedule.

Amgen hopes denosumab will reach well beyond those two treatment areas and has put it in trials that include cancer-related bone damage, prevention of bone metastases in prostate cancer and treatment of rheumatoid arthritis. It could be the company’s next drug to break $1 billion in sales. Analyst sales projections reach as high as $3.5 billion, though some are more conservative.

Drug is vital to company

There’s a lot riding on this drug.

Mitra Thompson, a research analyst with IHS Global Insight in London, writes in an e-mail that other drugs in Amgen’s portfolio are “either losing money or are simply not selling enough to curb the overall slump in turnover.”

“So denosumab’s approval by the FDA is doubly important for the company’s long-term prospects. If the FDA chooses not to approve denosumab, Amgen won’t have many other options left in its pipeline, and it could become a prime target for a takeover.”

How denosumab functions

Denosumab works by inhibiting the process that naturally breaks down bone in the body. The body regularly breaks down and builds up bone. By inhibiting the breakdown, denosumab leads to stronger, denser bones less susceptible to fracture.

For the Journal’s studies, researchers injected 60 milligrams of denosumab twice a year for three years into more than 7,800 post-menopausal women with osteoporosis. Compared with the placebo, denosumab reduced the women’s vertebral fractures by 68 percent, their hip fractures by 40 percent and nonvertebral fractures 20 percent. The Journal concludes that the reduction is “significant.”

In a second, smaller study of more than 1,400 elderly men undergoing hormone treatment for prostate cancer, researchers found a 62 percent decrease in new vertebral fractures.

Denosumab has a strong safety profile. The major concern about long-term use noted in the Journal relates to possible effects on the immune system, but researchers did not observe an increased rate of serious infections related to denosumab. They did report, however, significant increases in eczema and hospitalizations for cellulitis, a skin infection.

The FDA panel is expected to address Thursday whether there should be additional safety restrictions or studies. Regulators also have concerns about whether the drug may hasten tumor growth.

New alternative

Amgen has stressed that the twice-yearly injection is easier for patients than taking pills.

The early detection and treatment of those at risk of osteoporosis complications has created great strides in the past 15 years, said Dr. Felicia Cosman, clinical director for the National Osteoporosis Foundation.

In addition to lifestyle, nutrition and exercise guidelines, there have been dramatic changes in treatments, with several medications available.

“One of the big problems that we have in the field is that, for many reasons, people don’t seem to stay on their medication,” she said.

That’s why new drugs, such as denosumab, which offer another alternative for patients are welcome, she said.

Impact on stock price

Amgen’s stock rose $1.57 to close at $62.81 Tuesday.

Denosumab already has played heavily into Amgen’s share value. On July 8, a day after positive trial data were released, the company’s stock jumped 14 percent.

Denosumab was initially discovered about 15 years ago and the first studies in people began in 2001. The proposed trade name is “Prolia.”

According to Amgen’s annual filing, it expects growing competition among drug manufacturers working on new bone loss treatments, and “if denosumab is approved, we would need to significantly expand our sales and marketing capabilities to support its successful launch.”

The drug already is driving Amgen to grow in certain areas — hiring new staff and expanding its facilities in Puerto Rico to handle production.

Company spokeswoman Sarah Reines declined to speculate about whether the drug’s approval would result in new jobs. At the end of 2008, Amgen had 16,466 employees globally, about 6,500 of whom work in Thousand Oaks.

Amgen will handle its own commercialization for osteoporosis and oncology in the U.S., but the company has created an agreement with Daiichi Sankyo Co. to give that company exclusive rights to develop and commercialize denosumab in Japan, and recently announced it will work with GlaxoSmithKline to commercialize denosumab for osteoporosis in Europe, Australia, New Zealand and Mexico.

Source : www.venturacountystar.com

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FDA approves new drug indication for FORTEO

Eli Lilly and Company announced the Food and Drug Administration (FDA) has approved a new use for its osteoporosis drug FORTEO to treat osteoporosis associated with sustained, systemic glucocorticoid therapy in men and women at high risk of fracture. Glucocorticoid therapy is the most common cause of secondary osteoporosis, leading to bone loss and an increased risk for fracture, according to a statement from Eli Lilly.

Glucocorticoid-induced osteoporosis, or GIO, is associated with chronic use of glucocorticoid medications, which are often prescribed for inflammatory conditions such as rheumatoid arthritis and obstructive pulmonary disease. Data indicate that glucocorticoid medications are used by up to three out of every 100 adults over age 50.

Approximately 50 percent of individuals who are prescribed chronic glucocorticoid therapy will eventually have an osteoporotic fracture. The use of glucocorticoid medications can lead to a reduction in bone formation, the company said said. FORTEO has been shown to counter this effect by stimulating bone formation.

In the course of the FDA’s review of the new indication, Lilly provided data from a clinical study which showed that in patients with glucocorticoid-induced osteoporosis, FORTEO increased bone mineral density (BMD) from baseline to 18 months of treatment by 7.2 percent at the lumbar spine, 3.6 percent at the total hip, and 3.7 percent at the femoral neck.

“Until now, physicians and patients had only one class of approved therapy for the treatment of glucocorticoid-induced osteoporosis,” said Kenneth G. Saag, M.D., MSc, professor of medicine and epidemiology at the University of Alabama in Birmingham. “The approval of teriparatide for this new indication offers healthcare providers and patients a new treatment option that effectively increases bone mineral density in a different way than anti-resorptives.”

Source : www.modernmedicine.com

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MDRNA gets FDA nod for generic osteoporosis nasal spray

Shares of MDRNA Inc more than doubled after the company said U.S. health regulators approved its generic nasal spray to treat osteoporosis, adding that its partner Par Pharmaceutical Cos Inc had launched the product.

The calcitonin-salmon nasal spray is the copycat version of Miacalcin nasal spray that is marketed by Novartis (NOVN.VX) in the United States.

The nasal spray is indicated for the treatment of osteoporosis in females who have low bone mass, after five years or more of menopause, relative to healthy premenopausal females, Par Pharma said in a statement.

U.S. sales of Miacalcin were about $112 million in 2008, the company said, citing IMS Health data.

In March, Par agreed to buy MDRNA's abbreviated new drug application for the generic nasal spray and its cGMP manufacturing facility in Hauppauge, New York, for an upfront cash payment and profit sharing on sales of the drug for five years.

"Any revenue generated from that product will go into our RNA interference research programmes," MDRNA's spokesman Matthew Haines said.

However, Haines declined to give more details about the nuances of the profit-sharing agreement.

RNAi or gene silencing as a way to fight disease, is one of the hottest areas of biotechnology research and has attracted investment from a range of major drugmakers.

MDRNA currently has a liver cancer programme in preclinical stage development.

MDRNA shares touched a high of $3.55 before paring some gains to trade up about 90 percent at $2.94 Tuesday morning on Nasdaq. Shares of Par Pharma were up 1 percent at $14.70 on the New York Stock Exchange.

Source : www.reuters.com

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Fablyn Approved in Europe for the Treatment of Osteoporosis

Ligand Pharmaceuticals Incorporated today announced that its partner, Pfizer, Inc. has received approval from the European Commission(EC) for FABLYN® (lasofoxifene) Tablets, a selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in post-menopausal women at increased risk of fracture. FABLYN was submitted for approval in Europe in January 2008. This is the first regulatory approval for FABLYN, a product that stems from a 1991 research collaboration with Ligand.

As a result of the first approval of FABLYN in a major market, Ligand has earned a $3 million milestone payment. Pursuant to the 1991 research agreement and 1996 settlement agreement with Pfizer, Pfizer has elected to pay the milestone payment by returning 323,338 shares of stock it owns in Ligand. The shares are valued as of the date of the settlement agreement adjusted for Ligand's 2007 return of capital paid to Ligand shareholders. After the payment of this milestone, Pfizer owns a remaining 674,230 shares in Ligand.

Pfizer is responsible for the registration and worldwide marketing of FABLYN. Ligand is entitled to receive royalty payments on net sales of the product. In January 2009, Pfizer received a complete response letter from the FDA requesting additional information for FABLYN. On September 8, 2008, the FDA's Advisory Committee for Reproductive Health Drugs voted 9-3 (with one abstention) that there is a population of postmenopausal women with osteoporosis in which the benefits of lasofoxifene likely outweigh the risks. FDA is not required to follow the advice of the panel.

“Today's announcement is an exciting development for Ligand as the European approval of FABLYN marks the fourth drug associated with Ligand's research platform that has been approved and the second to be approved in just the past six months. This milestone payment reduces Ligand's outstanding shares and paves the way for potential future royalty payments and cash flow following the launch of the product,” said John L. Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. “We applaud Pfizer for its commitment and diligence in advancing the product to approval and developing an alternative treatment option for patients in Europe with osteoporosis.”

Osteoporosis Prevalence

The International Osteoporosis Foundation (IOF) reports that more than 75 million people suffer from osteoporosis in Europe, Japan and the U.S. About 30% of all post-menopausal women have osteoporosis in Europe and in the U.S., and at least 40% of them will suffer osteoporotic fractures in their lifetime. In Europe alone, 3.78 million osteoporosis-related fractures were reported in 2000, with an estimated cost of 32 billion euros. In the U.S., the National Osteoporosis Foundation projects an estimated 10 million American women to have osteoporosis in 2010 and almost 26 million to have osteopenia (low-bone mass), placing them at increased risk of osteoporosis.

About Ligand Pharmaceuticals

Ligand discovers and develops new drugs that address critical unmet medical needs of patients with muscle wasting, frailty, hormone-related diseases, osteoporosis, inflammatory diseases, anemia, asthma, rheumatoid arthritis and psoriasis. Ligand's proprietary drug discovery and development programs are based on advanced cell-based assays, gene-expression tools, ultra-high throughput screening and one of the world's largest combinatorial chemical libraries. Ligand has strategic alliances with major pharmaceutical and biotechnology companies, including Bristol-Myers Squibb, Celgene, Cephalon, GlaxoSmithKline, Schering-Plough, Pfizer and Wyeth Pharmaceuticals. With nine pharmaceutical deals and more than twenty different molecules in various stages of development, Ligand utilizes proprietary technologies for identifying drugs with novel receptor and enzyme drug targets.

Caution Regarding Forward-Looking Statements

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These statements include those regarding timing and results of clinical data for FABLYN and other drug candidates, data analysis and evaluation of FABLYN, utility or potential benefits to patients, the potential commercial market for FABLYN and plans for continued development and further studies of FABLYN. Actual events or results may differ from Ligand's expectations. For example, there can be no assurance that other trials or evaluations of FABLYN or other SERM-related product candidates will be favorable or that they will confirm results of previous studies, that data evaluation will be completed or demonstrate any hypothesis or endpoint, that FABLYN or other SERM-related product candidates will provide utility or benefits to certain patients, that any presentations will be favorably received, that FABLYN or other SERM-related product candidates will be useful as a single agent or in combination with other drugs, that marketing applications will be filed or, if filed, approved, or that clinical or commercial development of these product candidates will be initiated, completed or successful or that our rights to FABLYN and other SERM-related product candidates will not be successfully challenged. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases available at www.ligand.com as well as in public periodic filings with the Securities and Exchange Commission, available via www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this press release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Source : http://www.drugs.com/

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