A first-of-its-kind osteoporosis drug lowers the risk of bone fractures as well as or better than current medicines, studies in older women and men with prostate cancer suggest.
Advisers to the Food and Drug Administration will review those studies and other data on the safety and effectiveness of Amgen Inc.'s denosumab Thursday, then recommend whether the agency should approve the genetically engineered drug.
Wall Street sees it as a potential blockbuster crucial to Amgen's future. But given the crowded market of treatments for the bone-thinning disease, doctors see its expected high cost as a big drawback.
"It'll find a particular niche where it'll be used, but I don't see it as taking over the market," said Dr. Sundeep Khosla, a professor and osteoporosis researcher at the Mayo Clinic not involved in the studies.
Still, he called the drug a "tour de force of modern molecular medicine" because it is potent and was designed specifically to block one pathway involved in the natural breakdown of bone cells.
Denosumab, an injection just under the skin given only twice a year, would have to compete against eight pills and injected medicines, including estrogen and generic and brand-name Fosamax, the first drug approved for osteoporosis.
Most of those must be given more often, with pills swallowed once a day, week or month, a nasal spray inhaled daily, and one injection under the skin given daily. But another injection given intravenously is only needed once a year and estrogen, while out of fashion because of its link to breast cancer, is available in skin patches changed once or twice a week.
Those drugs' prices can range from about $120 a year for generic Fosamax to a few thousand dollars a year — still well below the typical price for a genetically engineered drug.
Dr. Lenore Buckley, a professor at Virginia Commonwealth University, said all these drugs carry some risks. The studies found denosumab caused eczema in some patients, and a dozen of the women got a serious skin infection, cellulitis, that sometimes required hospitalization for intravenous antibiotics.
"Because this drug affects the immune system, the long-term effects on cancer risk or immune function is still unknown," she warned, saying she expects FDA will require Amgen to track risks over time if the drug is approved.
The effectiveness of denosumab and existing drugs appears to plateau after two or three years, she added.
About 10 million Americans have osteoporosis, and another 44 million are at increased risk because of low bone density.
The two studies were released online Tuesday by the New England Journal of Medicine.
Both were paid for by Amgen, of Thousand Oaks, Calif. Nearly all the researchers receive consulting, advisory and other fees from the company and competitors, or are Amgen employees. The biotech company designed the studies, handled data collection and analysis, and helped write the journal reports.
One study included 7,868 women, aged 60 to 90, with moderate to severe osteoporosis. Half got denosumab injections every six months for three years. They had 68 percent fewer spine fractures and 40 percent fewer hip fractures than the other study participants who were given dummy shots.
The second study included 912 men with prostate cancer at increased fracture risk due to cancer hormone therapy. Denosumab cut the risk of spine fractures 62 percent over three years compared to dummy shots. Spine bone density loss was far smaller for those given the drug.
Until recent years, studies of osteoporosis drugs just measured changes in bone density, assumed to equate with lower risk of fracture. Newer studies also measure fracture rates, but there are no head-to-head studies comparing treatments — and probably won't be because the small differences in fracture rates would require studies of tens of thousands of patients.
However, based on some prior studies, independent experts say denosumab appears more effective at preventing spine fractures than three older pills — Fosamax, Actonel and Boniva — and calcitonin nasal sprays, which all use various pathways to slow down or kill cells called osteoclasts that break down bone. Experts think denosumab prevents spine fractures about as well as Reclast, an injected drug that slows bone breakdown, and injected Forteo, the only drug that stimulates bone-building cells called osteoblasts. And denosumab appears to prevent fractures of the hip, forearm and ankle about the same as those drugs.
Dr. Jacob Warman, an osteoporosis expert at Brooklyn Hospital Center, said he thinks denosumab might have potential as an add-on to existing drugs to improve results even more. He expects it would be covered that way by insurers, who commonly pay for multiple medicines for other conditions.
Amgen spokeswoman Kerry Beth Daly said the company has not yet set a price for the drug, but will try to keep it affordable. She said pricing also will reflect denosumab's twice-a-year dose schedule, given that about half the patients on existing drugs stop them within a year due to side effects or trouble keeping up with dose schedules.
On the Net: http://www.nejm.org