The Summer Vacation Edition

While most people were on summer vacation, NWHN trekked out to suburban Gaithersburg, Maryland to learn as much as possible about a new drug for osteoporosis – denosumab. At the end of the day, we were not convinced that this drug should be approved, and we told the FDA about our concerns in testimony delivered by Cindy Pearson, NWHN’s Executive Director.
Now we want to share what we learned with you. Although denosumab is not yet approved, its manufacturer has already started a marketing campaign. There aren’t any advertisements yet, but your clinician is likely to have heard of this new drug, and may be excited about the fact that it’s given as a shot every six months, making it by far the most convenient of all osteoporosis medications. We think that safety and effectiveness, not convenience, are the key issues – here’s what we found out.
At the FDA meeting we learned that denosumab has been studied in 7800 postmenopausal women who had osteoporosis and who were 72 years old, on average. Women were given shots of denosumab or a placebo every six months for three years. The women given denosumab had increased bone density and fewer fractures compared to the women given placebo shots. During the three year study period, 0.7% of women on denosumab had a hip fracture versus 1.2% of women on placebo. Less serious fractures were also diminished in women given denosumab. Similarly, a smaller study of younger postmenopausal women (average age 58) also showed that denosumab prevents bone loss even when fractures aren’t likely to occur. These are good effectiveness results; however, denosumab also caused significant health problems for women in these studies, including ovarian and cervical cancer, pancreatic cancer, breast cancer recurrences, and serious infections that required hospitalization. The numbers of cancers were too small to say with certainty that they were caused by denosumab, but the risk of serious infection seems to be real.
Clearly, denosumab is not completely safe, so the question becomes whether or not the benefits outweigh the risks. The numbers show that about 0.7% more women on denosumab had a serious infection than women on placebo – exactly the same fraction of women who avoided a hip fracture. The aftermath of a hip fracture is very serious for some women who never fully recover, but serious infections can be very dangerous, too, and led to at least one death in the denosumab studies.
In response to this dilemma, the Network told the FDA Advisory Committee that we thought the benefit of denosumab does not outweigh the risks, at least not yet. Any time a drug is being considered for long-term use by many people who will never benefit from it, information about its safety needs to be weighed very heavily. We believe that women deserve more information about the possible risk of cancer caused by denosumab, information that will only emerge as these trials are followed up for a longer period of time.