Amgen has announced the FDA ( Food and Drug Administration ) 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 RANK ligand ( RANKL ) inhibitor, is a subcutaneous injection administered by a health care professional every six months.

According to the National Osteoporosis Foundation, two 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 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 ).

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 –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 –3.5 were enrolled in the study.
Patients were randomized ( 1:1 ) to receive either 60 mg of Prolia 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.

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.

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.

Safety information

Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia. Prolia 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.

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.

In the Phase 3 pivotal study of women with postmenopausal osteoporosis ( n=7,808 ), serious infections leading to hospitalizations were reported more frequently in the Prolia-treated patient group. 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, including cellulitis. Endocarditis was reported more frequently in the Prolia-treated patient group.

Epidermal and dermal adverse events such as dermatitis, rashes and eczema have been reported. Discontinuation of Prolia should be considered if severe symptoms develop.

In clinical trials in women with postmenopausal osteoporosis, Prolia resulted in significant suppression of bone remodeling. The significance of these findings is unknown. The long-term consequences of the degree of suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as osteonecrosis of the jaw ( ONJ ), atypical fractures and delayed fracture healing. ONJ and atypical fractures have been reported in patients with Prolia. Patients should be monitored for these adverse outcomes.

The extent to which Prolia 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. While the risk is likely to be low, patients should be advised of this potential risk. ( Xagena )

Source: Amgen, 2012

XagenaMedicine2012