FDA Gives Amgen’s Prolia the Go-Ahead in Two Cancer Therapy-Induced Bone Loss Indications

FDA has approved two new indications for Amgen’s Prolia® (denosumab) for patients with breast and prostate cancer. The agency says that the drug can now be used to increase bone mass by women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and by men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer. 

The expanded indications for Prolia are based on two Phase III trials: a three-year, randomized, double-blind, placebo-controlled, multinational study involving 1,468 men with nonmetastatic prostate cancer undergoing androgen deprivation therapy, and a two-year, double-blind, placebo-controlled, multinational study involving 252 postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

In men, bone mineral density (BMD) was significantly higher at the lumbar spine in patients treated with Prolia for two years compared to placebo. Additionally, after three years of treatment with Prolia, differences in BMD were 7.9% at the lumbar spine, 5.7% at the (total) hip, and 4.9% at the femoral neck. The incidence of new vertebral fractures was 3.9% in the placebo-treated men compared to 1.5% for the Prolia-treated men, representing a relative risk reduction of 62%.

In women, BMD was higher at 12 months at the lumbar spine in patients treated with Prolia as compared to placebo. Additionally, after two years of treatment with Prolia, differences in BMD were 7.6% at the lumbar spine, 4.7% at the (total) hip, and 3.6% at the femoral neck.

The most common (per patient incidence >10%) adverse reactions reported with Prolia in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer were arthralgia and back pain, according to Amgen. Additionally, in Prolia-treated men with nonmetastatic prostate cancer receiving androgen deprivation therapy, a greater incidence of cataract adverse events was reported. Hypocalcemia was reported in Prolia-treated patients.

Prolia specifically targets RANK ligand, an essential regulator of osteoclasts, Amgen explains. It was approved in the U.S. last year first in June for the treatment of postmenopausal women with osteoporosis at high risk of fracture and then in November for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Prolia is approved in the EU for the treatment of osteoporosis in postmenopausal women at increased risk of fractures and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. 

Amgen is also studying denosumab in Phase III trials as a treatment for male osteoporosis and to prevent bone metastases in breast and prostate cancers. In Phase II, the drug is being evaluated in RA.