Progenics Pharmaceuticals, Inc. and Wyeth Pharmaceuticals, a division of Wyeth has announced positive results from a three-month open-label extension study of subcutaneous methylnaltrexone for the treatment of opioid-induced constipation (OIC) in patients with advanced illness. The results are scheduled to be presented at the Multinational Association of Supportive Care in Cancer (MASCC) Symposium in St. Gallen, Switzerland.
Eighty-two OIC patients completed a placebo-controlled phase III study (MNTX 302), and then participated in the three-month open-label extension study of subcutaneous methylnaltrexone. The goal of the extension study was to obtain efficacy and safety data on subcutaneous methylnaltrexone, administered as needed, for up to three months.
Forty-two OIC patients received subcutaneous methylnaltrexone previously in the double-blind MNTX 302 study, and then entered this open-label extension study. For these forty-two patients, the mean laxation response rates (laxation within four hours) were 45.5 per cent during the first month, 57.7 per cent in the second month, and 57.3 per cent in the third and final month. For the remaining forty patients who had first received placebo in the double-blind MNTX 302 study prior to entering this open-label extension study, laxation response rates were 48.3 per cent during the first month, 47.6 per cent in the second month, and 52.1 per cent in the third and final month.
Consistent with previous studies, subcutaneous methylnaltrexone was generally well-tolerated in the three-month open-label study, and the most common adverse event reported was abdominal pain which was typically mild-to-moderate in severity.
"These results show that methylnaltrexone, when administered subcutaneously for up to three months, continued to induce laxation in advanced illness patients with OIC," commented Paul J Maddon, MD, Progenics' founder, CEO and chief science officer. "These data were included in the most recent submissions to the US Food and Drug Administration and the European Medicines Agency. Progenics, and our collaborator, Wyeth, are encouraged by the positive effect of subcutaneous methylnaltrexone observed in our clinical trials."
Methylnaltrexone is a peripherally acting mu-opioid receptor antagonist that is designed to treat OIC without interfering with pain relief. Currently, there is no approved medication that specifically targets the underlying cause of OIC to relieve constipation in this patient population. In March 2007, Progenics submitted a New Drug Application (NDA) for subcutaneous methylnaltrexone to the United States Food and Drug Administration (FDA), followed in May 2007 by the submission of a marketing authorization application (MAA) in Europe to the European Medicines Agency (EMEA). Both regulatory submissions included the three-month open-label extension study data reported.
The NDA and MAA have been accepted and validated for review by the FDA and EMEA, respectively. The FDA has set a Prescription Drug User Fee Act (PDUFA) date of January 30, 2008 to complete its review of the NDA, and completion of the MAA review is expected to occur in 2008.