BETHESDA, MD 02 June 2010—Amgen on June 1 announced the licensing of denosumab injection for use in postmenopausal women who have osteoporosis and are at high risk for fracture.
The FDA-approved labeling for the drug, which will be sold as Prolia, defines a high risk for fracture as a history of osteoporotic fracture. Other indications are multiple risk factors for fracture or intolerance or lack of response to other osteoporosis treatments.
Prolia will be shipped to wholesalers by next week, Amgen stated. The product should be administered once every six months, according to the labeling.
Denosumab is a human IgG2 monoclonal antibody specific for the receptor activator of nuclear factor kappa-B ligand, or RANKL. The antibody inhibits RANKL-mediated osteoclast formation, resulting in decreased bone resorption.
In a placebo-controlled clinical trial involving 7808 women, twice-yearly 60-mg injections of denosumab were associated with a 68% reduction in vertebral fractures, a 20% decrease in nonvertebral fractures, and a 40% decrease in hip fractures, according to Amgen.
The recommended dosage of denosumab is a single 60-mg s.c. injection every six months administered in the upper arm, upper thigh or abdomen. Patients should receive 1000 mg of calcium and at least 400 IU of vitamin D daily during denosumab therapy.
According to the labeling, the most common adverse events reported by denosumab recipients in clinical trials were back or musculoskeletal pain, pain in the extremities, hypercholesterolemia, and cystitis.
The labeling warns that hypocalcemia may worsen during treatment with denosumab, especially in patients with severe kidney disease. In patients with normal kidney function, serum calcium levels reach their lowest point about 10 days after a denosumab injection.
Denosumab is contraindicated in patients with hypocalcemia but may be administered to those patients after the condition is corrected.
The labeling states that patients treated with denosumab are at increased risk for serious infections of the skin, abdomen, bladder, ear, and pericardium. These and other potential problems are described in a medication guide that must be given to patients with each filled prescription of the drug.
The medication guide is part of an FDA-mandated risk evaluation and mitigation strategy, or REMS, for the drug. The REMS also includes an outreach program for health care providers and postmarketing monitoring for adverse events.
Denosumab will be supplied in 60-mg/mL single-use syringes or vials packaged in cartons of one each. The product should be refrigerated at 4–8 degrees C in the original container until use. After the carton is removed from the refrigerator, the product must be kept at a temperature of 25 degrees C or less and used within 14 days.
