TUESDAY, Aug. 11, 2009 (HealthDay News) -- A new bone-building drug has worked well in a trial of men whose bones were weakened by the hormone therapy they were taking for prostate cancer, researchers report.
The drug, denosumab (Prolia), is a monoclonal antibody that Amgen Inc. hopes to market for fracture prevention, not only in men with prostate cancer but also for postmenopausal women who are taking hormone therapy for breast cancer. An advisory panel of the U.S. Food and Drug Administration is scheduled to meet this week to consider the Amgen application.
Results of the trial, reported online Aug. 11 in advance of publication in the Aug. 20 issue of the New England Journal of Medicine, will be part of the evidence submitted to the FDA panel. Anywhere from one-third to one-half of the 2 million American men receiving hormone-blocking therapy as treatment for prostate cancer are potential users of denosumab, said study author Dr. Matthew R. Smith, director of genitourinary medical oncology at Massachusetts General Hospital.
Denosumab blocks the activity of a molecule that causes destruction of bone cells. It thus counters the bone loss that results from lack of hormones, both male and female. The drug is given by intravenous injection, just once every six months.
The prostate cancer study was pioneering because "there have been no prior, large-scale fracture-preventing studies in men," Smith said. It enrolled more than 900 men being treated at 156 medical centers in the United States and Europe.
Over 24 months, bone density increased 5.6 percent in men who got denosumab and decreased 1 percent in men given a placebo, the researchers found. The 36-month incidence of spinal fractures was 1.5 percent among those receiving denosumab, while it was 3.9 percent among those given placebo.
Although denosumab is an "important" drug and "clearly effective based on the two studies that have been published (the other was in postmenopausal women)," its place in prostate cancer therapy has yet to be established, said Dr. Sundeep Khosla, a professor of medicine in the Endocrine Research Unit at the Mayo Clinic, who wrote an accompanying editorial.
A number of other drugs now are being used to help prevent fractures in men treated for prostate cancer, Khosla said. "Given other drugs that perhaps have similar efficacy, just where this drug will fit is unclear," he noted.
The main contender against denosumab appears to be a relatively new member of the bone-building bisphosphonate family, zoledronic acid (Zometa), Khosla said. It, too, is given intravenously, with only one injection a year required, he said. But zoledronic acid must be given by a physician, while denosumab can potentially be self-administered, he noted.
Cost can be an issue with these new drugs, Khosla said. A generic bisphosphonate can cost as little as $100 a year, while the wholesale price of zoledronic acid is $1,300 a year. It's not known yet what Amgen would charge for denosumab, Khosla said.
Whatever the price, "in certain subsets of patients it would be a good option," he said. Khosla agreed with Smith's estimate that one-third to one-half of all men getting hormone-blocking therapy could be in that subset.
Some concern about possible effects of denosumab on the immune system have been raised, Khosla noted, because the molecule it blocks plays a role in the immune response. A study of postmenopausal women noted some immunity-related problems, such as an increase in the incidence of eczema, he noted, but "I don't think there is any concern significant enough to warrant not approving the medication, although it warrants surveillance."
Prostate cancer and its treatment are described by the U.S. National Cancer Institute.