FDA panel gives nod to bone loss drug used in prostate cancer patients

August 27, 2009

The FDA Advisory Committee for Reproductive Health Drugs (ACRHD) has recommended approval of denosumab (Prolia) for prevention and treatment of bone loss in certain prostate cancer patients.

The FDA Advisory Committee for Reproductive Health Drugs (ACRHD) has recommended approval of denosumab (Prolia) for prevention and treatment of bone loss in certain prostate cancer patients.

Based on review of data from 30 studies of more than 12,000 patients, the committee moved to recommend approval of denosumab for the treatment of bone loss in patients receiving hormone ablation for prostate cancer, among other applications. The drug is a fully human monoclonal antibody that specifically targets RANK Ligand, an essential regulator of osteoclasts. The treatment is being evaluated for whether it can block all stages of osteoclast activity through a specific mechanism.

As part of the ACRHD recommendation, the panel urged that denosumab have a Risk Evaluation and Mitigation Strategy, possibly including a medication guide and a health care provider communications plan. There is a Prescription Drug User Fee Act action date of Oct. 19, 2009.

The news from the FDA panel comes in the wake of recently released results from a phase III study of the safety and efficacy of denosumab in reducing risk of fracture in men with non-metastatic prostate cancer being treated with androgen deprivation therapy.

The study, supported by Amgen and published in the New England Journal of Medicine (published online Aug. 11, 2009), involved 1,468 men who were treated subcutaneously with twice-yearly denosumab, 60 mg. Results of the randomized, double-blind, placebo-controlled study showed the men had significant increased bone mineral density, compared with placebo. There was also a 62% reduction in fractures of the vertebrae, compared with placebo, at the 36-month follow-up.

Additional findings at 24 months indicated a 6.7% BMD increase at the lumbar spine, compared with placebo. There were denosumab-induced increases in BMD at non-vertebral points as well (femoral neck: 3.9%; total hip: 4.8%), compared with placebo. Common adverse events related to denosumab included hypertension, back pain, constipation, arthralgia, and extremity pain.

"Bone loss is an early adverse effect and even short-term androgen deprivation therapy negatively impacts skeletal health," said first author Matthew Smith, MD, PhD, of Massachusetts General Hospital Cancer Center, Boston in a statement. "In this large international study, denosumab markedly increased bone mineral density and decreased the risk of fractures in many men receiving androgen deprivation therapy for prostate cancer."

For more on this study, check out the September issue of Urology Times.