FDA Approves New Indications for Prolia® (Denosumab) for the Treatment of Bone Loss in Patients With Prostate or Breast Cancer

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FDA Approves New Indications for Prolia® (Denosumab) for the Treatment of Bone Loss in Patients With Prostate or Breast Cancer Undergoing Hormone Ablation Therapy

Prolia is the First-and-Only Medicine Approved for Cancer Treatment-Induced Bone Loss

THOUSAND OAKS, Calif., Sept. 19, 2011 /PRNewswire via COMTEX/ --

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 (P=0.0125).

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.

About Prolia

Prolia is the first approved therapy that specifically targets RANK Ligand, an essential regulator of osteoclasts (the cells that break down bone).

Prolia is approved in the U.S. 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 also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer. In these patients with prostate cancer, Prolia reduced the incidence of vertebral fractures.

Prolia is approved in the European Union (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.

Prolia is approved in the U.S., Canada, Australia, and in all 27 EU member states as well as in Norway, Iceland and Liechtenstein. Applications in the rest of the world are pending.

Prolia is administered as a single subcutaneous injection of 60 mg once every six months. For further information on Prolia, including prescribing information and medication guide, please visit: www.prolia.com.

Important U.S. Safety Information

Prolia is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia. Hypocalcemia may worsen, especially in patients with severe renal impairment. All patients should be adequately supplemented with calcium and vitamin D. Patients receiving Prolia should not receive XGEVA®, as both Prolia and XGEVA contain the same active ingredient, denosumab.

In the Phase 3 pivotal study of women with postmenopausal osteoporosis (n=7808), 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 has been reported in patients with Prolia. Patients should be monitored for these adverse outcomes.

The most common adverse reactions (> 5 percent and more common than placebo) in patients with postmenopausal osteoporosis were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia and cystitis. Pancreatitis has also been reported. 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.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com. Follow us on www.twitter.com/amgen.