La Food and Drug Administration ( FDA ) has approved a new indication for Prolia ( Denosumab ) 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 health care professional every six months.
The new indication for Prolia is based on results from the ADAMO trial ( 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 greater than 5% ) were back pain, arthralgia and nasopharyngitis.
Approval was based on the ADAMO trial 12-month data. Men between the ages of 30 and 85 years with low BMD ( T-score less than or equal to -2.0 and greater than or equal to -3.5 at the lumbar spine or femoral neck ) or who have experienced a prior major osteoporotic fracture and had a T-score less than or equal to -1.0 and greater than or equal to -3.5 were enrolled in the study. Patients were randomized ( 1:1 ) to receive either 60 mg of Denosumab every six months or placebo.
All patients received daily Calcium and Vitamin D supplementation throughout the study.
The primary study endpoint was the percent change from baseline in the lumbar spine BMD at month 12. Secondary efficacy endpoints included percent change in total hip and femoral neck BMD from baseline to one year.
Denosumab is the first approved therapy that specifically targets RANK ligand, inhibiting osteoclast formation, function and survival.
Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia.
Hypocalcemia may worsen with the use of Prolia, especially in patients with severe renal impairment. All patients should be adequately supplemented with Calcium and Vitamin D.
Serious skin infections, as well as infections of the abdomen, urinary tract and ear, were more frequent in patients treated with Prolia. Patients should be advised to seek prompt medical attention if they develop signs or symptoms of severe infection. Endocarditis was reported more frequently in the Prolia-treated patients.
Epidermal and dermal adverse events such as dermatitis, rashes and eczema have been reported. Discontinuation of Prolia should be considered if severe symptoms develop.
Pancreatitis has also been reported with Prolia.
The extent to which Denosumab is present in seminal fluid is unknown. For men treated with Prolia, there is a potential for fetal exposure if the sexual partner is pregnant.
Source: Amgen, 2012