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FDA advisory committee vote: Denosumab benefits outweigh osteoporosis risks
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The FDA Advisory Committee for Reproductive Health Drugs voted unanimously that the benefits of denosumab treatment likely outweigh the risks for postmenopausal women with osteoporosis.
However, the committee did not recommend denosumab for preventive use in postmenopausal osteoporosis (12-3 vote) until more long-term data are available. They voted that denosumab should be limited to a high-risk subgroup of women with a history of fracture and patients who have failed or are intolerant to other therapeutic measures.
Denosumab is an investigational fully human monoclonal antibody that targets RANK Ligand.
"This is a unique therapy and is beneficial in women who do not tolerate other therapies," Julia V. Johnson, MD, vice chair of gynecology in the department of obstetrics and gynecology at the University of Vermont/Fletcher Allen Health Care, said during the meeting.
The committee was split on use of denosumab in patients with breast and prostate cancer undergoing hormone ablation therapy. The committee voted that denosumab was appropriate for the treatment of bone loss associated with the treatment of hormone ablation therapy in men with prostate cancer receiving androgen therapy, but not women with breast cancer.
Because of safety concerns, the committee did not recommend approval of denosumab for preventive indications.
"We know that when this drug stops, bone mineral density does plummet," said Sandra Carson, MD, committee chair and professor of obstetrics and gynecology at Warren Alpert Medical School of Brown University. "Although the treatment may be effective, it is related to unknown risks that may not make the benefit of prevention worthwhile."
Other safety issues identified in clinical trials include occurrence of serious infection, development of new malignancies, potential for tumor progression in patients with cancer and suppression of bone remodeling.
Committee members reviewed data from 30 studies that included more than 30,000 patients exposed to denosumab for about five years.
The FDA is scheduled to make a decision in October. If approved, denosumab would be marketed by Amgen under the brand name Prolia. While the FDA is not required to follow the advisory committee's recommendation, it usually does. - by Jennifer Southall
The voting by the FDA reflects a concern about safety of the drug and, at the moment, it seems that this will be approved for use in patients who are at high risk for fracture, but not as initial therapy for most patients.
- Donald A. Bergman, MD
Endocrine Today Editorial Board member
These votes are not surprising because all of the data that have been shown, other than fractures, have been very favorable with minimal side effects. I am surprised by some of the negatives; it is not going to be a tier 1 drug, we know this. There is no question that the biology is fabulous and it has all come together and is well done and well reported. It is worth emphasizing that, to my knowledge, all drugs are approved only after they demonstrated and improved effective. The rules for getting an osteoporosis drug approved are held to a higher standard.
- Michael Kleerekoper, MD
Endocrine Today Editorial Board member