2 Positive Studies Published on Experimental Drug Denosumab; FDA Panel Review This Week
WebMD Health News
Reviewed By Louise Chang, MD
Aug. 11, 2009 -- The experimental drug denosumab may be on its way to becoming the newest way to treat osteoporosis.
Denosumab, a biological drug given by injection every six months, looks safe and effective, researchers report in today's advance online edition of the New England Journal of Medicine.
An FDA advisory panel will meet Aug. 13 to decide whether to recommend denosumab for FDA approval. The FDA often follows the advice of its advisory committees, but it doesn't have to.
Denosumab works differently than other osteoporosis drugs. It binds to a protein called RANKL, which cells called osteoclasts need to break down bone as part of the bone remodeling process.
The idea behind denosumab is to slow the bone-breakdown process in people whose bones are already dangerously thin.
WebMD first reported on denosumab in September 2008, when news about the drug's potential to treat osteoporosis in postmenopausal women was presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.
In both studies, patients got a shot of either denosumab or a placebo every six months for three years. And in both studies, fractures were rarer in patients taking denosumab.
In the postmenopausal osteoporosis study, which included 7,800 women 60-90 years old with osteoporosis, new vertebral fractures occurred in 2.3% of patients taking denosumab, compared with 7.2% of patients taking the placebo.
That's a difference of 68%, notes researcher Steven Cummings, MD, director of the San Francisco Coordinating Center at the California Pacific Medical Center and a professor of medicine and epidemiology at the University of California at San Francisco.
"It's more effective for reducing vertebral fractures than I expected ... 68% is a very powerful reduction," Cummings tells WebMD.
In the prostate cancer study, which included more than 1,400 men with prostate cancer on bone-weakening hormone therapy, new vertebral fractures occurred in 1.5% of patients taking denosumab, compared with 3.9% of patients who got the placebo.
"To see this very dramatic 62% decrease in vertebral fractures in three years in this relatively high-risk population of men is very impressive," researcher Matthew Smith, MD, PhD, tells WebMD. Smith is the director of genitourinary medical oncology at Massachusetts General Hospital Cancer Center.
Denosumab's Side Effects
Denosumab didn't show an increased risk of infection or cancer -- risks seen with other types of biologic drugs -- in either trial.
Denosumab also wasn't linked to osteonecrosis of the jaw (sometimes called "jawbone death"), which has been reported with other osteoporosis drugs called bisphosphonates.
Denosumab's safety profile "appeared excellent" in the prostate cancer study, Smith says, adding that the study was the first large study of fracture prevention in men.
"Previously, there had been no large studies to address that problem in men with prostate cancer, and frankly, not in men in any setting," Smith says.
Both denosumab studies were sponsored by the drug's maker, Amgen. Smith and Cummings disclose working as consultants for Amgen, and several researchers on both studies are Amgen employees.
Denosumab "seems at least as efficacious as the currently approved alternatives," states an editorial published with the studies.
But editorialist Sundeep Khosla, MD, of the Mayo Clinic's medical school in Rochester, Minn., notes that there haven't been any head-to-head trials comparing denosumab to other osteoporosis drugs, that the drug's longer-term safety isn't known yet, and that cost could be an issue if denosumab is pricey. Khosla notes no conflicts of interest.
Cummings says there are plans to follow the patients in his study for at least 10 years. He also hopes that patients will be more compliant about taking denosumab than other osteoporosis drugs.
"It's as effective as any other treatment and can be given twice a year as a simple injection, like a flu shot" and can be given by a nurse or primary care doctor, Cummings says.
Susan Bukata, MD, an osteoporosis specialist and associate professor of orthopaedics at New York's University of Rochester Medical Center, says denosumab would be "another option" for people who can't or won't take other osteoporosis drugs, such as people with kidney failure or gastrointestinal issues.
"There's definitely a place for this drug," Bukata says. "I think still, the gold standard is we start on the pills, we start on the generics. But this is certainly a good second-line choice and for some patients ... this may be my first-line choice."
Bukata wasn't involved in the denosumab trials. She discloses that she expects to soon work on a clinical trial of another Amgen drug.
SOURCES: Cummings, S. The New England Journal of Medicine, Aug. 11, 2009; advance online edition. Smith, M. The New England Journal of Medicine, Aug. 11, 2009; advance online edition. Kholsa, S. The New England Journal of Medicine, Aug. 11, 2009; advance online edition. Matthew Smith, MD, PhD, director of genitourinary medical oncology, Massachusetts General Hospital Cancer Center. Steven Cummings, MD, director, San Francisco Coordinating Center, California Pacific Medical Center, professor of medicine and epidemiology, University of California, San Francisco. Sundeep Khosla, MD, Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minn. Susan Bukata, MD, associate professor of orthopaedics, University of Rochester Medical Center, Rochester, N.Y.
©2009 WebMD, LLC. All Rights Reserved.