Progenics Pharmaceuticals, Inc plans to advance oral methylnaltrexone for the treatment of opioid-induced constipation (OIC) into late stage clinical development and will commence a phase 2b/3 clinical trial of a methylnaltrexone tablet in chronic-pain patients in the second half of 2010. Progenics also announced data from a clinical trial of this methylnaltrexone tablet.

The tablet form of oral methylnaltrexone was developed by Progenics' former collaboration partner Wyeth. At the time of Wyeth's acquisition by Pfizer in October 2009, Progenics regained from Wyeth the rights to methylnaltrexone, including rights to this methylnaltrexone tablet. The transfer of data and information to Progenics regarding Wyeth's work on oral methylnaltrexone was recently completed and Progenics has now had the opportunity to review in detail information regarding the methylnaltrexone tablet which is being reported.

The study of the methylnaltrexone tablet was conducted in subjects with chronic, non-cancer pain receiving various opioid treatment regimens. Study inclusion criteria required subjects to have a history of OIC. Subjects were administered a single methylnaltrexone tablet at different dose levels following an overnight fast. Forty-eight per cent of subjects receiving one of the doses (n=25) laxated within four hours of treatment.

Progenics' analysis and next steps for the methylnaltrexone tablet

Based on the study data reported in this release and other information regarding oral methylnaltrexone, Progenics believes that the methylnaltrexone tablet is active and generally well tolerated. Both the time to onset of action demonstrated in this study and the percentage of patients who had responded within four hours are consistent with that previously shown in clinical trials of subcutaneous methylnaltrexone.

"We believe that the activity demonstrated to date by the methylnaltrexone tablet shares the hallmarks of methylnaltrexone: both a prompt onset of action and a predictable response for a large percentage of patients," said Paul J Maddon, founder, chief executive officer and chief science officer of Progenics. "Our next step is to initiate a phase 2b/3 dose-optimizing clinical trial in chronic-pain patients with OIC in the second half of this year to confirm these results."

The tablets to be used in Progenics' planned phase 2b/3 trial were produced by Wyeth at Wyeth's cost as provided for under the provisions of the termination of the collaboration between the two companies.

Opioids are considered to be effective analgesics for the management of moderate-to-severe pain, and one of the most common side effects of opioids is constipation.

Methylnaltrexone selectively displaces opioids from the mu-opioid receptors outside the CNS, including those located in the gastrointestinal tract, thereby decreasing their constipating effects.