New Osteoporosis Drug Reduces Fractures
The first member of a new class of osteoporosis drugs reduced spinal fractures by about two-thirds in post-menopausal women and in men undergoing hormone-deprivation therapy for prostate cancer, according to two studies released online today by the New England Journal of Medicine.
The drug, called denosumab, is the first to block production of cells called osteoclasts that break down bones, and physicians have high hopes for it because of its efficacy, ease of administration and apparent lack of severe side effects. But it is also a biological agent rather than a chemical, meaning it's difficult to produce, and it is likely to be the highest-priced osteoporosis drug in an already-crowded marketplace.
The most well-known of these drugs, Fosamax, is in a class known as bisphosphonates. These drugs actually kill osteoclasts, but carry the risk of stomach and esophogeal irritation and have been linked to some cases of jaw necrosis. Already, many insurance companies are pushing physicians to prescribe alendronate -- the generic version of Fosamax -- because it only costs about $100 per year.
Amgen, the manufacturer of denosumab, has not yet said how much the drug will cost, but analysts expect it to be at least $2,000 per year -- and potentially much higher -- and predict yearly sales of $2 billion to $3 billion.
But some medical experts think a high price will discourage use. "If it is going to be quite a bit higher than the next-most-expensive drug, I don't see that it is going to be used so widely," said Dr. Frederick Singer, director of the endocrine/bone disease program at John Wayne Cancer Institute in Santa Monica, who was not involved in the research.
Also, half or more of the women taking Fosamax and other osteoporosis drugs stop taking them within a year. Because denosumab requires only two injections per year that can be done at home, physicians hope women will be much more likely to stick to it.
An advisory committee of the Food and Drug Administration will meet Thursday to consider Amgen's application for approval of the drug, to be called Prolia, for treating osteoporosis in women and in men being treated for prostate cancer. If approved, it would be the first drug specifically approved for treating such men, although bisphosphonates have been approved for treating simple osteoporosis.
The overall market for osteoporosis drugs is estimated at more than $5 billion per year because of the large potential patient population. As many as half of women and 30% of men will suffer an osteoporosis-related fracture during their lifetime, according to the International Osteoporosis Foundation. About a third of the 2 million American men with prostate cancer undergo hormone-deprivation therapy in an effort to prevent release of the hormones that fuel the growth of tumors, which sharply increases their risk of osteoporosis.
The two new trials were designed and funded by Amgen, and most of the researchers were Amgen employees or recipients of funds from the company. Nonetheless, osteoporosis experts were impressed with the results. "From a scientific standpoint, these are outstanding publications," Singer said.
The first study included 7,686 women ages 60 to 90. Half were given an injection of denosumab every six months for three years, and half received a placebo. Overall, 2.3% of women receiving the drug had a spinal fracture and 0.7% had a hip fracture, compared with 7.2% and 1.2% in the placebo group. That is similar to or slightly better than results with bisphosphonates, although the drugs have not been compared head-to-head.
The drug "does everything you would want a drug to do in women to prevent fractures," said Dr. John S. Adams, an orthopedic surgeon at UCLA's Geffen School of Medicine.
The second study involved 1,468 prostate cancer patients receiving hormone-deprivation therapy. They underwent the same protocol as the women. Overall, 1.5% of men receiving the drug had a spinal fracture, compared with 3.9% of those in the placebo group. Men receiving the drug also had a 5.6% increase in bone mineral density, while those receiving placebo had a 1% decline. There was no decline in non-spinal fractures.
Previous studies have shown that other osteoporosis drugs can increase bone density in such men, but this is the first one to show that a drug can reduce fractures, the authors said.
Many of the patients in both studies reported soreness at the injection site and transient bone pain similar to arthritis. The drug caused eczema, an inflammation of the epidermis, in a few patients, and about 12 of the women got a serious skin infection called cellulitis. Some earlier, small studies showed an apparent small increase in tumors in treated patients, but that was not observed in either of the new studies. Such potentially severe side effects will be a focus of the FDA panel.
The researchers also did not observe osteonecrosis of the jaw.
"My guess is that the [FDA] panel will probably be persuaded by these data to allow approval and release of the drug," Adams said.
"This appears to be the most potent of the osteoporosis drugs," Singer said, "but it will require very careful monitoring to look for rare side effects," which did not show up for other drugs until large numbers of people had received them.