FDA approves new indication for denosumab for bone loss in men with osteoporosis at high risk for fracture

September 21, 2012

FDA approved a new indication for denosumab (Prolia, Amgen) as a treatment to increase bone mass in men with osteoporosis at high risk for fracture.

FDA approved a new indication for denosumab (Prolia, Amgen) as a treatment to increase bone mass in men with osteoporosis at high risk for fracture.

Prolia, the first FDA-approved RANK Ligand inhibitor, is a subcutaneous injection administered by a healthcare professional every 6 months.

"While osteoporosis and osteoporosis-related fractures are more commonly associated with postmenopausal women, osteoporosis in men is a significant issue that is increasing in prevalence as life expectancies rise," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a press release.

According to the National Osteoporosis Foundation, 2 million men in the United States have osteoporosis and another 12 million are at risk. Osteoporosis and osteoporotic fractures in men remain under diagnosed and under treated.

The new indication for Prolia is based on results from the ADAMO trial3 (A multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of DenosumAb 60 mg every six months versus placebo in Males with Osteoporosis), the pivotal phase 3 study involving 242 men with low bone mineral density (BMD). In the study, treatment with Prolia resulted in significantly greater gains at the lumbar spine when compared to placebo (5.7 % vs. 0.9%). Effects of Prolia on BMD were independent of age, baseline testosterone levels, BMD status, and estimated fracture risk.

Additional results showed that patients in the study who received treatment with Prolia experienced BMD increases at all other skeletal sites assessed compared to placebo, including at the total hip (2.4% vs 0.3%) and at the femoral neck (2.1% vs 0.0%). Safety findings were consistent with what have been observed in other studies of Prolia in postmenopausal women with osteoporosis. The most common adverse reactions reported (per patient incidence >5%) were back pain, arthralgia, and nasopharyngitis.

Approval was based on the ADAMO trial 12-month data. Men between aged 30 and 85 years with low BMD (T-score ≤–2.0 and ≥–3.5 at the lumbar spine or femoral neck) or who have experienced a prior major osteoporotic fracture and had a T-score ≤–1.0 and ≥–3.5 were enrolled in the study. Patients were randomly assigned (1:1) to receive either 60 mg of Prolia every 6 months or placebo. All patients received daily calcium and vitamin D supplementation throughout the study.

The primary study end point was the percent change from baseline in the lumbar spine BMD at month 12. Secondary efficacy end points included percent change in total hip and femoral neck BMD from baseline to 1 year.Prolia is also approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.

Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating denosumab. Denosumab is contraindicated in women who are pregnant and may cause fetal harm. Patients receiving Prolia should not receive Xgeva (denosumab), as both Prolia and Xgeva contain the same active ingredient, denosumab.