Amgen (NASDAQ: AMGN) today announced that the U.S. Food and Drug Administration (FDA) approved two new indications for Prolia® (denosumab) as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer. In patients with prostate cancer, Prolia also reduced the incidence of vertebral fractures. Prolia is the first-and-only therapy approved by the FDA for cancer treatment-induced bone loss in patients undergoing hormone ablation therapy.
Aromatase inhibitors are often used in patients with breast cancer to prevent recurrence of disease, and androgen deprivation therapy is often used in patients with prostate cancer to prevent or control recurrent disease. These treatments reduce hormone levels, leading to bone loss and an increased risk of fracture.
"Bone loss and fractures are recognized adverse effects of hormone ablation therapies but we have not had an approved treatment option to prevent these problems for our patients," said Matthew Smith, M.D., Ph.D., director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, Boston. "Prolia now gives us the ability to reduce the risk of bone loss and fractures, allowing patients to continue their treatment and their fight against cancer."
The expanded indications for Prolia are based on two Phase 3 clinical trials: a three year, randomized, double-blind, placebo-controlled, multinational study involving 1,468 men with non-metastatic 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.(i)
In men, bone mineral density (BMD) was significantly higher at the lumbar spine in patients treated with Prolia for two years compared to placebo (-1.0 percent placebo, +5.6 percent Prolia; treatment difference 6.7 percent [95 percent CI: 6.2, 7.1]; P<0.0001). Additionally, after three years of treatment with Prolia, differences in BMD were 7.9 percent at the lumbar spine, 5.7 percent at the (total) hip and 4.9 percent at the femoral neck and the incidence of new vertebral fractures was 3.9 percent in the placebo-treated men compared to 1.5 percent for the Prolia-treated men, representing a relative risk reduction of 62 percent.
In women, BMD was higher at 12 months at the lumbar spine in patients treated with Prolia as compared to placebo (-0.7 percent placebo, +4.8 percent Prolia; treatment difference 5.5 percent [95 percent CI: 4.8, 6.3]; P<0.0001). Additionally, after two years of treatment with Prolia differences in BMD were 7.6 percent at the lumbar spine, 4.7 percent at the (total) hip and 3.6 percent at the femoral neck.
The most common (per patient incidence > 10 percent) 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 are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Additionally, in Prolia-treated men with non-metastatic prostate cancer receiving androgen deprivation therapy, a greater incidence of cataract adverse events was reported. Hypocalcemia was reported in Prolia-treated patients.