Phase 2 trial results of a pre-planned exploratory analysis in postmenopausal women
THOUSAND OAKS, Calif. (November 13, 2005) – Amgen (NASDAQ: AMGN), the world's largest biotechnology company, today announced that twice-yearly subcutaneous injections of denosumab (60 mg), (previously referred to as AMG 162), increased bone mineral density (BMD) in the lumbar spine, total hip, distal 1/3 radius and total body compared to placebo at 24 months. The study also included an open label Fosamax®* (alendronate) arm. Investigators reported on a pre-planned exploratory analysis at the American College of Rheumatology Annual Scientific Meeting in San Diego, California.
The ongoing, multi-center, phase 2 dose-ranging trial includes results from 337 healthy postmenopausal women with low BMD who completed two years of study. Researchers reported denosumab 60mg increased BMD of the lumbar spine by 7.4 percent in women administered the therapy twice yearly and 6.2 percent for Fosamax® 70mg weekly. Across all doses and dosing intervals, denosumab increased the BMD of the lumbar spine by 4.3 to 9.0 percent over baseline.
"The two-year results showed the continued effect of denosumab in increasing bone mineral density in postmenopausal patients with low bone mass," said Michael Lewiecki, MD, clinical assistant professor of medicine, University of New Mexico School of Medicine, Albuquerque, NM. "These data suggest denosumab, when administered twice a year, may offer a promising alternative for the prevention and treatment of osteoporosis."
Denosumab is designed to target RANK Ligand, a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANK Ligand overwhelms the body's natural defense against bone destruction.
Preclinical models have demonstrated that inhibiting RANK Ligand leads to significant improvements in cortical and trabecular bone density, volume and strength.
Denosumab is currently being studied for its potential in a broad range of bone loss conditions including osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and rheumatoid arthritis.
"Because denosumab targets RANK Ligand, it functions in a way that is entirely different than other bone loss treatments," said Willard Dere, MD, senior vice president of global development and chief medical officer, Amgen. "We believe its unique, targeted approach to regulating bone loss may have the ability to transform how we treat these conditions."
Researchers also reported twice-yearly injections of denosumab (60 mg) increased total hip BMD by 5.1 percent after 24 months. Fosamax® 70 mg weekly produced a 3.4 percent increase during the same time period. Denosumab, at all doses and dosing intervals studied, increased total hip BMD from 2.8 to 5.1 percent. Across all doses and dosing intervals, distal 1/3 radius BMD increased from 0.6 to 2.5 percent, and total body BMD increased from 0.9 to 4.5 percent.
Occurrence of adverse events was similar among the denosumab, placebo, and Fosamax® groups and showed no new pattern of events in the second year of treatment. No neutralizing antibodies to denosumab were observed throughout the two years.
Denosumab (AMG 162) Study Design
Investigators randomized 412 postmenopausal women, average age 63, with low BMD to receive denosumab, placebo or Fosamax®. The purpose of the study was to determine the safety and efficacy of denosumab on lumbar spine BMD compared with placebo at 12 months. The doses of denosumab 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 denosumab via subcutaneous injection. Patients receiving Fosamax® followed the approved indication and oral dosing instructions of 70 mg once weekly.
At entry, the women averaged –2.1 on their T-scores, a densitometric 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).
The Need for Bone Loss Treatments
Bone loss represents a significant clinical and economic burden. Osteoporosis is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. In the U.S. today, 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis.
Of the 10 million Americans estimated to have osteoporosis, eight million are women and two million are men. In addition, one in two women and one in four men over age 50 will have an osteoporosis-related fracture in their remaining lifetime.
In Europe, recent estimates have stated that approximately 3.8 million people have experienced bone fractures related to osteoporosis.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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