Amgen's Phase III Osteoporosis Study Is Company's Largest Clinical Program
This article was originally published in The Pink Sheet Daily
Executive Summary
Clinical trials for Amgen's bone loss therapy AMG 162 will look at the entire spectrum of bone health, VP-R&D Perlmutter says. Phase II studies demonstrated lower incidence of dyspepsia and more rapid absorption than Fosamax, he says.
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Amgen has embarked on a global Phase III registration program for its osteoporosis agent AMG 162. "We have underway a massive global registration enabling program which looks at post-menopausal osteoporosis and amelioration of hormone ablation-induced bone loss, and this is a worldwide program," Amgen Executive VP-R&D Roger Perlmutter, MD/PhD, said at the UBS life sciences conference in New York Sept. 29. "It represents the largest clinical program that Amgen has ever undertaken by any measure, and it is an extraordinarily deep and robust registration." AMG 162 is a human monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL), a key mediator of the resorptive phase of bone remodeling. The agent is administered every six months by subcutaneous injection. In Phase II trials, AMG 162 was compared to placebo and Merck's Fosamax (alendronate) for one year. Dyspepsia "was observed in 4% of patients receiving placebo and 5% of patients receiving AMG 162 but in 20% of patients who received alendronate," Perlmutter said. Response rates also differed for the two osteoporosis agents, he noted. "The effect of AMG 162 is exceedingly rapid. You can measure changes in bone turnover within hours….Disphosphonates are poorly absorbed. They intercalate into bone and reach a steady state over a period of months." Merck released a study Sept. 28 claiming an efficacy advantage for Fosamax versus Aventis/Procter & Gamble's osteoporosis agent Actonel (risedronate). P&G responded that the study was not properly designed (see 1 (Also see "Merck Fosamax Study Shows Benefit Vs. Actonel; Aventis/P&G Fault Endpoint" - Pink Sheet, 29 Sep, 2004.)). The Amgen exec said the entire spectrum of bone health will be addressed in the Phase III program. That includes "not just post-menopausal osteoporosis and male osteoporosis, but indeed hormone ablation associated osteoporosis, osteoporosis associated with other treatments like glucocorticoid-induced osteoporosis and also the osteoporosis associated with inflammatory disease, as for example in rheumatoid arthritis." Amgen has initiated Phase II studies to examine the effect of AMG 162 on rheumatoid arthritis. Preclinical studies suggest "the combination of AMG 162 and Enbrel could have a very dramatic effect in this setting," Perlmutter said. Amgen's TNF-inhibitor Enbrel (etanercept) received an indication to induce major clinical response in patients with rheumatoid arthritis Sept. 28 (2 (Also see "Amgen Polishes Enbrel Label" - Pink Sheet, 28 Sep, 2004.)). The company also stated that enrollment in its colorectal carcinoma agent panitumumab Phase III U.S. trial has slowed dramatically following the approval of Bristol-Myers Squibb/Imclone's oncologic agent Erbitux (cetuximab). - Andrew Shelton |