A first-of-its-kind osteoporosis drug lowers the risk of bone fractures better than some existing treatments, two studies suggest, and soon could add a more expensive but easier-to-manage treatment option to the booming market.
Amgen Inc. will stress that only two shots of its genetically engineered denosumab, which could be approved for sale this fall, are needed each year. That's important, because many patients stop taking other drugs due to side effects or frequent dosing.
Wall Street sees denosumab as a potential blockbuster crucial to Amgen. But with many cheaper, heavily advertised treatments, doctors view its expected high cost as a drawback. Genetically engineered drugs, made by altering a cell's DNA or other genetic material, all cost more than $10,000 a year.
"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.
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Still, he called the drug a "tour de force of modern molecular medicine" because it is potent and was designed by making antibodies cloned over and over from cells in the lab to block one pathway involved in the how the body naturally breaks down bone cells.
Denosumab would be the first osteoporosis treatment that is such a monoclonal antibody — a type of immune cell cloned from the same parent cell to bind to a specific substance. In this case, it targets a molecule in bones that drives formation of cells called osteoclasts that break down bone, a strategy that greatly reduces bone loss.
The Food and Drug Administration on Tuesday released its review of denosumab, with its staff citing concerns about increased rates of skin infections and some tumors. That report comes just ahead of a meeting Thursday when outside advisers will weigh the drug's safety and effectiveness and recommend whether to approve it.
Denosumab, an injection just under the skin, would have to compete against eight major types of pills and injected medicines, including estrogen and generic and brand-name Fosamax pills, long the market leader.
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 needed only once a year, and estrogen, while out of fashion due to its link to breast cancer, is available in skin patches changed once or twice a week.
Those drugs' annual retail cost can range from $385 for generic Fosamax to roughly $1,250 for most brand-name pills to $11,100 for injected Forteo, which must be injected daily.
Global sales of osteoporosis treatments, including hundreds of vitamin brands, hit nearly $8.4 billion last year, according to data from IMS Health, which studies drugs. About 10 million Americans have osteoporosis.
Analyst Steve Brozak of WBB Securities said denosumab will pass the $1 billion annual sales threshold for blockbusters, but it's unclear by how much.
"You're going to have blowback by insurers" over how much they will pay, he said, but Amgen might try to charge more than $10,000 per year.
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 the 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.
The two studies were released Tuesday by the New England Journal of Medicine.
Amgen, of Thousand Oaks, Calif., paid for both. 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 ages 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 study participants who got dummy shots.
The second study included 1,468 men with prostate cancer at increased fracture risk due to cancer hormone therapy, although 556 dropped out for reasons including side effects and cancer progression to the study being extended from two to three years. Denosumab cut the risk of spine fractures 62 percent over three years compared with dummy shots. Spine bone density loss was far smaller for those given the drug.
Until recently, studies of osteoporosis drugs measured only changes in bone density, assumed to equate with lower fracture risk. Newer studies also measure fracture rates, but there are no head-to-head studies on that.
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 cells called osteoclasts that break down bone.
