PROGENICS, WYETH BEGIN TRIAL OF POSTOPERATIVE ILEUS DRUG

Progenics Pharmaceuticals and Wyeth Pharmaceuticals have announced the initiation of the first of two global Phase III trials to evaluate the safety and efficacy of intravenous methylnaltrexone for the treatment of postoperative ileus, a debilitating impairment of the gastrointestinal tract that occurs after surgery. There are no medicines currently approved to treat postoperative ileus.

The cause of postoperative ileus is not clear, but release of endogenous opioids in response to the trauma of surgery is believed to be involved. The problem can be exacerbated by the administration of opioids, such as morphine, to relieve postoperative pain. Methylnaltrexone is a mu-opioid-receptor antagonist that does not cross the blood-brain barrier. It is designed to reverse certain peripheral side effects caused by opioids, particularly in the gastrointestinal tract, while not interfering with brain-centered pain relief.

In a pilot Phase II trial previously conducted by Progenics, patients who received methylnaltrexone following segmental colectomy exhibited improvements in clinically important measures of gastrointestinal recovery.

The first Phase III study will enroll approximately 500 patients who have undergone segmental colectomy surgery in a double-blind, randomized, placebo-controlled trial at approximately 90 surgical centers worldwide. Key elements of the study design, including the primary efficacy endpoint, were reviewed by the FDA under a special protocol assessment in July. In this trial, study medication (methylnaltrexone, at one of two dose levels, or placebo) will be administered following surgery and every six hours until the patient recovers gastrointestinal function, or for up to 10 days after surgery.

The intravenous form of methylnaltrexone currently under investigation for the treatment of postoperative ileus has received fast-track designation from the FDA, which facilitates development and may expedite regulatory review. The companies plan to begin a second global Phase III study of intravenous methylnaltrexone later this year.