The European Commission (EC) has granted marketing authorization for the RANK ligand inhibitor denosumab (Prolia) for treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. The European approval of Prolia marks its first approval worldwide. Amgen, the manufacturer of Prolia, announced the EC authorization on May 28, 2010.
On June 1, the US Food and Drug Administration approved Prolia for postmenopausal women with osteoporosis who are at high risk for fractures—defined as having a history of osteoporotic fracture, or multiple risk factors for fracture, or failure to respond to or tolerate other available therapy for osteoporosis—but not for men with prostate cancer. Prolia decreases destruction of bone and increases bone mass and strength. An injection of Prolia is recommended once every 6 months.
Safety and efficacy of Prolia in treatment of postmenopausal osteoporosis that led to its approval in the US were demonstrated in a 3-year, randomized, double-blind, placebo-controlled trial of 7,808 postmenopausal women 60–91 years of age. In the study, Prolia reduced the incidence of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis.
The most common side effects reported with Prolia include back pain, pain in the extremities, musculoskeletal pain, high cholesterol levels, and urinary bladder infections. Serious adverse reactions include hypocalcaemia; serious infections, including infections of the skin; and dermatologic reactions such as dermatitis, rashes, and eczema. Because Prolia causes significant suppression of bone turnover, it may contribute to osteonecrosis of the jaw, atypical fractures, and delayed fracture healing.
Prolia was approved with a risk evaluation and mitigation strategy (REMS) that includes a Medication Guide for patients and communications to healthcare providers that explains the risks and benefits of the drug.