Phase 2 one-year trial results in postmenopausal women released at American Society for Bone And Mineral Research Annual Meeting
SEATTLE (October 03, 2004) – Amgen Inc. (NASDAQ: AMGN), the world's largest biotechnology company, today announced that at all doses studied, twice yearly injections of AMG 162, the company's investigational therapy for bone loss, significantly increased bone mineral density (BMD) at the total hip compared with placebo at 12 months. AMG 162, at all doses, also increased total hip BMD, similar to or greater than that resulting from FOSAMAX® (alendronate)* treatment in the same time frame.
The one year results of the ongoing multi-center, Phase 2, dose ranging trial in healthy postmenopausal women with low BMD were presented at the American Society for Bone and Mineral Research (ASBMR) 26th Annual Meeting in Seattle. This double blind trial was designed to evaluate the safety and efficacy of AMG 162 compared with placebo with an open label cohort comparison to FOSAMAX®.
"This study suggests that AMG 162 significantly improves bone mineral density in postmenopausal patients experiencing bone loss," said Michael McClung, MD, FACE, principal investigator of the AMG 162 study and founding director of the Oregon Osteoporosis Center in Portland. "The medical community should be very encouraged by these data that suggest AMG 162, when administered twice a year, may offer a promising alternative for the treatment of osteoporosis."
"With the development of AMG 162, Amgen scientists have validated an entirely new pathway and novel mechanism of action for addressing conditions associated with bone loss," said Beth Seidenberg, MD, chief medical officer and senior vice president of global development, Amgen. "These Phase 2 results with our investigational agent are very compelling and give us great confidence as we actively enroll and initiate our pivotal trial."
The effects of AMG 162 (at 60 mg twice yearly) at the total hip BMD were significantly (p<0.001) greater than FOSAMAX® (at 70 mg once weekly) at 12 months. AMG 162 across all doses and dosing intervals increased the BMD of the lower spine by 4 to 7 percent, similar to the 5 percent increase in the FOSAMAX® group, after 12 months of treatment. AMG 162 also had a positive effect on BMD at the hip, distal 1/3 radius, and total body.
In this trial, AMG 162 was well tolerated. The most common adverse event in any of the treatment groups was dyspepsia (4 percent, 5 percent and 20 percent in the placebo, AMG 162 and the open label FOSAMAX® groups, respectively).
The company recently announced the initiation of a pivotal Phase 3 study of AMG 162 in postmenopausal women with osteoporosis. Ongoing investigations of AMG 162 also are evaluating treatment-induced bone loss, rheumatoid arthritis (RA) and bone metastases.
About AMG 162
AMG 162 is an investigational, fully human monoclonal antibody with a unique mechanism of action that exclusively targets and binds with high affinity to, and inhibits the activity of human RANK (receptor activator of nuclear factor kappa B) Ligand, the primary mediator of bone resorption. Amgen scientists have confirmed the essential role of RANK Ligand pathway in the formation, activation and survival of osteoclasts, the cells that are associated with bone resorption.
RANK Ligand is responsible for osteoclast-mediated bone loss in a range of conditions including osteoporosis, treatment-induced bone loss (bone loss due to glucocorticoid treatment and immunosuppression), rheumatoid arthritis, bone metastases and multiple myeloma. The body naturally produces a protein called osteoprotegerin (OPG) to modulate the effects of excess RANK Ligand. OPG acts as a decoy receptor, preventing RANK Ligand from binding to its receptor, RANK, on the surface of osteoclasts and osteoclast precursors. By binding to RANK Ligand, OPG prevents the formation and activation of osteoclasts and helps keep the bone loss process in check. Amgen developed AMG 162 to mimic the effects of OPG, enhancing the body's own process to specifically inhibit the effects of RANK Ligand.
Observations from pre-clinical studies confirm that inhibition of RANK Ligand activity demonstrates significantly greater effects on blocking bone resorption compared to other therapies. The preclinical studies also showed that inhibition of RANK Ligand resulted in improvements in bone mass, bone density and bone strength, indicating that bone quantity and quality were improved. These studies, conducted by Amgen, also documented that inhibition of Rank Ligand activity does not interfere with the function of osteoblasts, the cells involved in bone formation.
AMG 162 Study Design
Investigators randomized 411 postmenopausal women, average age 63, with low lumbar spine BMD to receive AMG 162, placebo or FOSAMAX®. The primary endpoint of the study was to determine the safety and efficacy of AMG 162 on lumbar spine BMD compared with placebo. A secondary endpoint evaluated the cohort of patients randomized to receive open label FOSAMAX®. The doses of AMG 162 evaluated included 6, 14 or 30 mg every three months or 14, 60, 100 or 210 mg every six months. The researchers administered all doses of AMG 162 via subcutaneous injection. Patients receiving FOSAMAX® followed the approved indication and oral dosing instructions of 70 mg once weekly.
At entry, the women averaged -2.2 ± 0.8 on their T scores, an X-ray-based rating of BMD in which scores between -1.0 and -2.5 indicate osteopenia (thinning bone) and below -2.5 indicate osteoporosis, according to the World Health Organization (WHO).
Osteoporosis is a disease characterized by low bone mass and structural deterioration that causes bones, most commonly of the hip, wrist and spine, to become brittle and susceptible to fracture. Approximately 200 million women worldwide suffer from osteoporosis, according to the International Osteoporosis Foundation. An osteoporosis-related hip fracture may limit mobility and lead to a loss of independence. A vertebral fracture can result in loss of height and stooped posture, as well.
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