Biannual Shot May Be More Effective Than Oral Weekly Bisphosphonate
Peggy Peck
[One more on AMG 162, mainly because I don't think there is a place to file osteoporosis related material. This time the material comes from Medscape. The potential pay-out for Abgenix lies still 4 - 5 years away. And who knows what might happen in the meantime? So it shouldn't really effect the valuation of the stock at this time.]
Oct. 5, 2004 (Seattle) — The investigational agent AMG 162, an antibody that inhibits the molecular cascade that leads to bone loss, appears to remain active and effective for as long as six months after a single subcutaneous injection, according to results reported at the 26th annual meeting of the American Society for Bone and Mineral Research (ASBMR).
"AMG-162 has potent antiresorptive effects, which suggest that it has the potential to be a promising new therapy that can be administered in a very convenient form," said Michael McClung, MD, director of the Oregon Osteoporosis Center in Portland. In an oral presentation, Dr. McClung reported on phase II studies of AMG 162, which is being developed by Amgen. The drug is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa B ligand (RANKL). The aim of AMG 162 is to inhibit osteoclastic bone resorption.
The phase II studies recruited 411 postmenopausal women with low lumbar spine bone mineral density (BMD). Mean age of the women was 63 years, and the mean T score was -2.2. The women were randomized to placebo, AMG 162 in three-month doses (6 mg, 14 mg, or 30 mg) AMG 162 in six-month doses (14 mg, 60 mg, 100 mg, or 210 mg), or to weekly oral alendronate (70 mg).
After 12 months, the 60-mg six-month dose of AMG 162 proved significantly more effective in BMD in the hip than once-weekly administration of alendronate 70 mg (P < .001). The other doses of AMG 162 improved BMD by 4% to 7%, which was comparable to weekly alendronate, which demonstrated a 5% BMD gain. The alendronate patients received their medication on an open-label basis. All of the treatment groups showed marked improvement in BMD compared with placebo. Those patients either had no BMD improvement or experienced declines.
Dr. McClung also described improvements with AMG 162 and alendronate in the distal third of the radius and in total body BMD. "This study demonstrates that AMG 162 significantly improves BMD in postmenopausal patients experiencing bone loss," he said.
"These results are very surprising," said Uri Liberman, MD, PhD, professor of physiology and medicine at Tel Aviv University in Israel. "It is surprising that the antibody will continue to be active in the circulation for as long as six months. This will make the drug a strong competitor with the bisphosphonates. However, we know that the drugs such as alendronate are very safe. We have 10 years of experience with them. The question will remain as to what the side effects are going to be with this antibody." Dr. Liberman was not involved in the study.
"This is a major development," said Clifford Rosen, MD, a past president of the ASBMR and a clinical professor of nutrition at the University of Maine and director of the Maine Center for Osteoporosis Research in Bangor. "What AMG 162 does is to remove the excess bad guys that are responsible for bone loss," he explained. "Bone remodeling is a balancing act that is supposed to help make bones stronger." He suggested that AMG 162 will help keep that balance in order.
Dr. Rosen, who was not involved in the study, explained that the RANK ligand is responsible for the formation, activation, and survival of the osteoclasts. To modulate the effects of RANKL the body creates osteoprotegrin to bind to the ligand and keep production of osteoclasts in check. In osteoporosis, RANKL overwhelms the body's natural osteoprotegrin causing excessive bone resorption. AMG 162 acts by mimicking osteoprotegrin, which helps to balance the bone formation process.
The ease of administration is a major benefit for AMG 162 in that it will not require many office visits, Dr. Rosen said. "The cost is anybody's guess," he added, noting that drugs developed by biotechnology companies have never been inexpensive. But he echoed Dr. Liberman's concern about potential toxicity. "We don't have long-term safety data for this antibody," he said.
ASBMR 26th Annual Meeting: Abstract 1072. Presented Oct. 3, 2004.
Reviewed by Gary D. Vogin, MD
medscape.com |
