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FDA committee: Denosumab safe, effective to treat bone loss associated with ADT-treated prostate cancer
There was a lack of data on efficacy in breast cancer; none of prevention indications were recommended for approval.
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The FDA Advisory Committee for Reproductive Health Drugs was split on the use of denosumab — an investigational fully human monoclonal antibody that targets RANK Ligand — in patients undergoing hormone ablation therapy for the treatment of breast or prostate cancer. Although the committee voted that denosumab effectively treated bone loss associated with hormone ablation therapy in men with prostate cancer, they said there was a lack of evidence of the drug’s efficacy in patients undergoing hormone ablation therapy for breast cancer.
The drug was also not recommended for the prevention of bone loss in patients with breast or prostate cancer.
“Although the treatment may be effective, it is related to unknown risks that may not make the benefit of prevention worthwhile,” said Sandra Carson, MD, chair of the committee and professor of obstetrics and gynecology at Warren Alpert Medical School of Brown University. “We know that when this drug stops, bone mineral density does plummet; however, we are talking about long-term use here and we better be convinced of its safety.”
Safety issues identified in clinical trials include occurrence of serious infection, development of new malignancies and potential for tumor progression in patients with cancer. In addition, data on histomorphometry suggest suppression of bone remodeling, which may lead to delayed fracture healing or atypical fracture with long-term use and dermatologic adverse events.
The drug’s efficacy was also being reviewed to treat postmenopausal osteoporosis. The committee voted unanimously that the benefit of denosumab treatment in postmenopausal women with osteoporosis likely outweighs the risk. However, the committee did not recommend the drug, in a 12-3 vote against, for preventive use in postmenopausal osteoporosis until more long-term data are available.
The general consensus was 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.
“This is a unique therapy and 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.
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 about denosumab in October. If approved, denosumab would be marketed by Amgen under the brand name Prolia. Although the FDA is not required to follow the advisory committee’s recommendation, it usually does. – by Jennifer Southall