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Intravenous Methylnaltrexone Fails in Phase 3 Trial
Preliminary results from the phase 3 clinical trial conducted by Wyeth showed that treatment did not achieve the primary end point of the study: a reduction in time to recovery of gastrointestinal function (i.e., time to first bowel movement) as compared to placebo. The study also did not show that secondary measures of surgical recovery, including time to discharge eligibility, were superior to placebo. In this clinical study, methylnaltrexone was administered intravenously in doses of 12 or 24 mg every six hours and was generally well tolerated.
“Currently, we are conducting the necessary analyses to determine greater clarity regarding the outcome of this clinical study, ” states Paul J. Maddon, M.D., Ph.D., Progenics’ Founder, Chief Executive Officer, and Chief Science Officer. “Preliminary findings from this international study of 542 patients are inconsistent with the clinically meaningful results demonstrated in the 65-patient phase 2 study of intravenous methylnaltrexone for the management of postoperative ileus.”
The second phase 3 trial of intravenous methylnaltrexone for management of POI is being led by Progenics and is similar in design to the Wyeth study reported today. Progenics announced on January 8, 2008 that it had completed enrollment in this trial, with results expected to be reported by midyear.
“Despite the results of this phase 3 trial for POI, we remain confident in the methylnaltrexone development program,” says Robert Ruffolo, Ph.D., President, Research and Development, Wyeth Pharmaceuticals. “We will continue to develop the methylnaltrexone franchise to help address the unmet medical need of patients suffering with the gastrointestinal side effects of opioids.”
The Wyeth and Progenics development program for methylnaltrexone continues in multiple formulations across multiple patient populations. Following is the status of intravenous, subcutaneous, and oral formulations of methylnaltrexone currently under investigation.
In addition to the two studies in segmental colectomy patients, the companies are conducting a phase 3 study of intravenous methylnaltrexone for the management of POI in patients who have undergone surgical repair of large abdominal hernias. Those results are expected to be reported in early 2009.
Wyeth and Progenics are awaiting a decision from the United States Food and Drug Administration (FDA) by the end of April 2008 on marketing approval of their subcutaneous formulation of methylnaltrexone for use in the palliative care setting for opioid-induced constipation (OIC). The companies filed the New Drug Application (NDA) with the FDA for this indication in March 2007. Wyeth and Progenics are also conducting clinical studies evaluating the subcutaneous formulation of methylnaltrexone for the treatment of opioid-induced constipation in the chronic pain setting, in patients with non-malignant pain (phase 3), and in the acute pain setting, in patients following orthopedic rehabilitation (phase 2).
The Companies are conducting two phase 2 trials evaluating oral formulations of methylnaltrexone for the treatment of OIC with findings expected to be reported mid-2008.
Source: Wyeth Pharmaceuticals and Progenics Pharmaceuticals