Amgen presents nearly two dozen abstracts from Romosozumab and Prolia® (Denosumab) at ASBMR

Amgen (NASDAQ:AMGN) today announced that it will present data from several romosozumab and Prolia® (denosumab) studies at the American Society for Bone and Mineral Research (ASBMR) 2013 Annual Meeting in Baltimore from Oct. 4-7, 2013.

Romosozumab data include results from the Phase 2 study that demonstrate significant increases in volumetric bone mineral density. Romosozumab is being developed in collaboration with UCB. Prolia data include 19 abstracts, featuring several on long-term safety and efficacy data from the open-label extension study of the pivotal Phase 3 fracture trial for up to eight years.

“We are very encouraged by the long-term safety and efficacy data with Prolia treatment as well as by the clinical data we see from our pipeline bone-building molecule, romosozumab,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “Amgen has led nearly a decade of clinical work in bone biology and, with fracture rates on the rise, we remain committed to advancing medicines that help treat bone disease.”

SELECTED ABSTRACTS OF INTEREST INCLUDE:

Abstracts are available on the ASBMR website at www.asbmr.org and updated data will be presented at the meeting.

Prolia Abstracts of Interest:

• Eight Years of Denosumab Treatment in Postmenopausal Women With Osteoporosis: Results From the First Five Years of the FREEDOM Extension
  Abstract LB-MO26, Late Breaking Abstract Session, Monday, Oct. 7, 10:35 – 10:40 a.m. EDT (Discovery Hall-Hall C)

• Denosumab Significantly Increases Bone Mineral Density Compared With Ibandronate and Risedronate in Postmenopausal Women Previously Treated With an Oral Bisphosphonate Who are at Higher Risk for Fracture
  Abstract 1018, Oral Presentation, Saturday, Oct. 5, 8:15 – 8:30 a.m. EDT (Hall A)

• Further Reduction in Nonvertebral Fracture Rate Is Observed Following Three Years of Denosumab Treatment: Results With Up to Seven Years in the FREEDOM Extension
  Abstract 1017, Oral Presentation, Saturday, Oct. 5, 8:00 – 8:15 a.m. EDT (Hall A)

Romosozumab Abstract of Interest:

• Effect of Romosozumab on Lumbar Spine and Hip Volumetric Bone Mineral Density (vBMD) as Assessed by Quantitative Computed Tomography (QCT)
  Study 20060326, Oral Presentation, Saturday, Oct. 5, 9:15 – 9:30 a.m. EDT (Hall A)

About Osteoporosis

Postmenopausal osteoporosis (PMO) affects many women after menopause1-2 and is a disease that weakens bones over time, making them thinner and more likely to break.2

In PMO, bone-removing cells get rid of bone at a rate that is too fast.3 This puts postmenopausal women with osteoporosis at risk for breaking a bone.3 Such a break, or fracture, may be a life-changing event. About half of all women over age 50 will have an osteoporosis-related fracture, and once that happens, the chances of another are much higher.4 According to the National Osteoporosis Foundation, women who have suffered a hip fracture are at a four-times greater risk of a second one.4

The World Health Organization has officially declared osteoporosis a public health crisis, while the International Osteoporosis Foundation urges governments worldwide to make osteoporosis a healthcare priority.

Osteoporosis-related fractures are responsible for an estimated $19 billion in costs annually in the U.S., and are expected to rise to approximately $25 billion by 2025.5 The direct medical cost of osteoporotic fractures in Europe is expected to rise from €31.7 billion in 2000 to €76.7 billion in 2050.6

About Romosozumab

Romosozumab is a bone-forming agent that inhibits sclerostin. It is currently being studied for its potential to reduce fracture risk in an extensive global Phase 3 program. This program includes two pivotal studies evaluating romosozumab against both placebo and active comparator in more than 10,000 women with postmenopausal osteoporosis. Romosozumab is being developed in collaboration with UCB.

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 nonmetastatic prostate cancer. In these patients with prostate cancer, Prolia reduced the incidence of vertebral fractures.

Prolia is indicated for treatment to increase bone mass in men 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 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. Prolia is contraindicated in women who are pregnant and may cause fetal harm. Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Patients receiving Prolia should not receive XGEVA® (denosumab), as both Prolia and XGEVA contain the same active ingredient, denosumab.

Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of 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. In the pivotal Phase 3 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 and atypical femoral fractures have 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. The most common adverse reactions in men with osteoporosis were back pain, arthralgia and nasopharyngitis. Pancreatitis has also been reported with Prolia in patients with osteoporosis. 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.

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.

Important EU Safety Information

The most common (≥1 percent) adverse reactions in clinical trials with Prolia in postmenopausal women with osteoporosis and breast or prostate cancer patients receiving hormone ablation were pain in extremity, urinary tract infection, upper respiratory tract infection, sciatica, cataracts, constipation, rash and eczema. Skin infections (predominantly cellulitis) leading to hospitalisation were reported more commonly in the Prolia group compared with placebo (0.4 percent vs. 0.1 percent) in postmenopausal osteoporosis studies. In breast and prostate cancer studies, serious adverse reactions of skin infection were similar in the Prolia and placebo groups (0.6 percent vs. 0.6 percent). In the Phase 3 placebo-controlled clinical trial in patients with prostate cancer receiving androgen deprivation therapy (ADT), an imbalance in cataract adverse events was observed with Prolia compared with placebo (4.7 percent vs. 1.2 percent placebo). No imbalance in cataract adverse events was observed in postmenopausal women with osteoporosis or in women undergoing aromatase inhibitor therapy for nonmetastatic breast cancer.

Prolia may rarely lead to hypocalcaemia. Prolia is contraindicated in patients with hypocalcaemia, and pre-existing hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before initiating therapy. Patients with severe renal impairment or receiving dialysis are at greater risk of developing hypocalcaemia. In the post-marketing setting, rare cases of severe symptomatic hypocalcaemia have been reported in patients at increased risk of hypocalcaemia. Osteonecrosis of the jaw (ONJ) has been reported rarely in clinical studies in patients receiving denosumab at a dose of 60 mg every 6 months for osteoporosis. In the osteoporosis clinical trial program, atypical femoral fractures were reported rarely in patients treated with Prolia. In the post-marketing setting, rare events of drug-related hypersensitivity, including anaphylactic reaction, have been reported in patients receiving Prolia. Hypersensitivity to the active substance or any of the excipients is a contraindication for Prolia.

Prolia is not recommended for use in pregnant women.

Denosumab Commercialization Collaborations

In July 2009, Amgen and GlaxoSmithKline announced a collaboration agreement to jointly commercialize Prolia for postmenopausal osteoporosis in Europe, Australia, New Zealand and Mexico once the product is approved in these countries. Amgen will commercialize Prolia’s postmenopausal osteoporosis and potential oncology indications in the U.S. and Canada and for all oncology indications in Europe and in other specified markets.

In addition, GlaxoSmithKline will register and commercialize denosumab for all indications in countries where Amgen does not currently have a commercial presence, including China, India and South Korea but excluding Japan. The structure of the collaboration allows Amgen the option of an expanded role in commercialization in both Europe and certain emerging markets in the future.

Amgen and Daiichi Sankyo Company, Limited have a collaboration and license agreement for the development and commercialization of denosumab in Japan.