Washington Editor

Adolor Corp.'s stock hit a springboard, bouncing up about 31.3 percent Wednesday after the company released positive data from its first Phase III study of lead product alvimopan in the management of postoperative ileus.

The top-line results from the 450-patient trial (known as study 302) are expected to help Adolor and partner GlaxoSmithKline plc (GSK), of London, reach their goal of filing a new drug application by the end of 2003, Bruce Peacock, president and CEO of Exton, Pa.-based Adolor, told BioWorld Today.

Adolor's stock (NASDAQ:ADLR) closed Wednesday at $12.95, up $3.09.

Alvimopan, formerly ADL 8-2698, is a mu opioid antagonist designed to selectively block the unwanted effects of opioid analgesics on the gastrointestinal (GI) tract. Potentially a first-in-class compound, alvimopan also is being evaluated in Phase III studies for the treatment of bowel dysfunction associated with the chronic use of opioids.

In the postoperative ileus (POI) Phase III, Adolor hit its primary endpoint of time to recovery in GI function.

"Study 302 was in patients who are undergoing certain types of abdominal surgeries in which they receive opioids [like morphine] to treat their pain," Peacock said. "Opioids do a good job of treating pain because they bind to, in this case, the mu opioids receptor. Those same receptors are in the GI tract and when they bind to the receptors, they can prolong the GI tract shutdown that occurs post-surgery.

"So a patient goes into the hospital and has surgery. After a couple of days they feel well enough to recover, but they can't eat and they can't have a bowel movement, and the opioids have slowed down their recovery," Peacock said. "Our drug is an antagonist to those opioid receptors, only in the GI tract though, so it doesn't interfere with the pain mechanism of the opioid in the central nervous system."

Study 302 was a double-blind, placebo-controlled, multicenter study of patients who were scheduled to undergo partial colectomies, simple or radical hysterectomies and to receive opioid analgesics. Patients were randomized in three arms of 150 each to receive placebo, 6 mg or 12 mg doses of alvimopan, at least two hours prior to surgery, and then twice a day beginning on the first postoperative day until hospital discharge, or for a maximum of seven days postoperative treatment, the company said.

The primary endpoint was a composite measure of the time to recovery of both lower and upper GI function as defined by time to first flatus or first bowel movement, and time to tolerability of solid foods, whichever occurred last. While there was a statistically significant difference in the 6 mg treatment group vs. the placebo group, the difference in the 12 mg group was not statistically significant, although a positive trend was seen.

And for secondary endpoints, including hospital discharge orders written, the company said a difference in favor of the alvimopan 6 mg treatment group vs. placebo was observed.

Meanwhile, Adolor has three other Phase III studies under way in POI. Specifically, the company has completed accrual for study 306, a 500-patient safety trial, and two others, studies 308 and 313 (450 patients each), should be accrued by the end of the second quarter, Peacock said.

"It is difficult to predict when results would be available, but our target is the third quarter," he said.

In November, Adolor reported top-line results from a 168-patient Phase III trial (study 304) in opioid bowel dysfunction patients. The primary endpoint was proportion of patients having a bowel movement within eight hours after each dose of the study medication during the 21-day treatment period. On average, the portion of patients who had at least one bowel movement within eight hours of each dose was 43 percent (p<0.001 vs. placebo) for alvimopan 0.5 mg, 55 percent (p<0.001 vs. placebo) for alvimopan 1 mg and 29 percent for placebo.

"[Study] 304 was very positive in our view. The plan for this year is to do more work exploring optimal dosing regimen, so we may, for example, explore whether we should titrate the dose up," Peacock said. "Do patients respond in a different way? We'll also do some longer-term toxicity testing and then we'll need longer-term studies in those types of patients to be able to move forward."

Adolor's deal with GSK was said to be potentially worth $270 million when it was signed about a year ago. It included a $50 million up-front fee paid by GSK. (See BioWorld Today, April 16, 2002.)

Peacock said it also includes milestones related to regulatory applications and approval. The companies share development costs inside the U.S., while GSK handles development elsewhere and would be required to pay Adolor royalties. The undisclosed U.S. profit split is not 50-50, Peacock said.