Investors await bone drug data from Amgen

BOSTON (Reuters) - Results due next week from a trial of Amgen Inc's experimental osteoporosis drug denosumab will represent a pivotal moment for the world's biggest biotechnology company as it struggles with declining sales of its flagship anemia drugs.

Data to be presented next Tuesday at a meeting of the American Society of Bone Mineral Research in Montreal will likely determine whether the drug is a multi-billion dollar product or an also-ran. Expectations are running high.

"Denosumab is a mega-blockbuster opportunity and will now emerge as the principal long-term value driver," said Steven Harr, an analyst at Morgan Stanley, in a recent research note. "We see a high probability of regulatory success given data to date."

Earlier this year, Amgen said denosumab significantly reduced the risk of spine fracture in a three-year trial of 7,800 post-menopausal women. The company did not say exactly how much the risk was reduced. On Tuesday it will.

Investors will be looking to see how the drug, which is given twice a year by injection, stacks up in a competitive, $6 billion-odd osteoporosis market dominated by a group of drugs known as bisphosphonates that include Merck & Co Inc's Fosamax, Sanofi-Aventis SA and Procter & Gamble Co's Actonel, Novartis AG's Reclast, and Boniva, from Roche Holding AG and GlaxoSmithKline Plc.

Currently the most effective drug in reducing vertebral fracture risk over a three-year period is Reclast, known in Europe as Aclasta, which reduced the risk by 70 percent in clinical trials. That is the benchmark against which denosumab will be measured.

"We view any comparable risk reduction of 65 percent to 70 percent or greater as a success for denosumab and believe it could eventually become the dominant treatment for osteoporosis," said Joel Sendek, an analyst at Lazard Capital Markets, in a research report.

A reduction in fracture risk of between 50 percent and 60 percent would place it roughly on a par with Fosamax, Boniva, and Eli Lilly and Co's Evista, which is a member of a different class of drugs known as selective estrogen-receptor modulators.

Any figure under 50 percent would be considered a serious disappointment, Sendek said.

Amgen's shares have risen roughly 18 percent since the company reported the initial positive results on July 25; but the devil will lie in the details of the full results, and also in the safety profile.

Thousand Oaks, California-based Amgen has said the most common side effects seen in the trial, known as FREEDOM, were mild joint and muscle aches. Investors will be closely watching to see whether there is any increase in the rate of infection in patients taking denosumab. An earlier trial showed an increase in the infection rate.

If the infection rate were not significantly higher than for the placebo, denosumab's safety profile could be significantly better than that of bisphosphonates, which bind to the bone and can stay in the body for years after treatment is stopped.

Earlier this year, the U.S. Food and Drug Administration said it is reviewing hundreds of cases of patients taking bisphosphonates who reported severe and even incapacitating pain in muscles, joints and bones. The pain occurred days, months or years after starting the bisphosphonate.

In addition, the agency said last year that it would study bisphosphonates after two reports in the New England Journal of Medicine found increased rates of serious atrial fibrillation in patients who took either Fosamax or Reclast.

A study published earlier this year in the Archives of Internal Medicine showed that Fosamax was linked with an 86 percent higher risk of newly detected atrial fibrillation than patients who never used the drug.

Merck has said it found no increased link in its clinical trials.

Merck said in an e-mail that a causal association has not been established between the use of bisphosphonates and reports of bone, muscle and joint pain. And the company said detailed analysis has not shown any statistically significant increase in atrial fibrillation in patients taking Fosamax. The Merck pill is also sold as a generic.

Amgen says denosumab does not stay in the body after treatment is stopped, meaning any side effects are more likely to be reversible. That is because unlike bisphosphonates, which bind to the bone, denosumab inhibits proteins that activate bone-destroying cells. When treatment is stopped, the drug leaves the body. That could give the drug a significant advantage over its rivals.

Roughly 10 million people in the United States and 200 million worldwide suffer from osteoporosis.

(Reporting by Toni Clarke, editing by Gerald E. McCormick, Bernard Orr)