A team of executives from Adolor Corp. and partner GlaxoSmithKline plc Tuesday said statistically significant data from a second Phase III study of Entereg in the management of postoperative ileus nudges the companies one step closer to submitting a regulatory package next year.
Wall Street responded Tuesday in the same way it did in April, when the companies released positive data from the first Phase III trial. Tuesday, Adolor's stock (NASDAQ:ADLR) rose $4.33, or 29.1 percent, to close at $19.38. In April, it gained $3.09, or 31.3 percent, to close at $12.95. (See BioWorld Today, April 3, 2003.)
Leading a conference call, Bruce Peacock, president and CEO of Exton, Pa.-based Adolor Corp., said the companies expect to file a new drug application for Entereg (alvimopan) in postoperative ileus late in the first half of 2004.
"Clearly this is an important product for us, it is our lead compound, and, clearly, the positive data in this study are an important step in being able to file an application," Peacock told BioWorld Today. "There are two more studies to go - studies 308 and 306, which is largely a safety study. We'll see the results from those two, and our target is to file late in the first half."
Entereg (formerly ADL 8-2698) is a mu opioid antagonist designed to selectively block the unwanted effects of opioid analgesics on the gastrointestinal tract. It is potentially a first-in-class compound. In addition to trials in postoperative ileus, Entereg also is being tested in the treatment of bowel dysfunction associated with the chronic use of opioids.
Postoperative ileus, or POI, often is associated with patients undergoing open abdominal surgery. It is characterized by pain, abdominal distention or bloating, nausea and vomiting, accumulation of gas and fluids in the bowel and delays in the passage of flatus or stool. There are no FDA-approved drugs for management of POI.
Top-line data from the trial released Tuesday (Study 313) demonstrate that a statistically significant difference was achieved in the primary endpoint - time to recovery of gastrointestinal function - in the Entereg 6-mg and 12-mg treatment groups, when each is compared to placebo.
The double-blind, placebo-controlled, multicenter trial enrolled 510 patients who were scheduled to undergo small bowel resections, large bowel resections or radical hysterectomies and who were receiving opioids for pain. Participants were randomized to receive placebo, 6-mg or 12-mg doses of Entereg 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.
The company said mean times of recovery were 120 hours, 105 hours and 98 hours for placebo, 6-mg, and 12-mg dose, respectively. That equates to mean times to recovery of gastrointestinal function that are approximately 15 hours and 22 hours sooner for the Entereg 6-mg and 12-mg treatment groups, respectively, Bruce Wallin, Adolor's vice president of clinical research and development, said on the conference call. He said a difference in favor of Entereg was noted in the secondary endpoints, as well, including time to hospital discharge written order in the 6-mg group and a statistically significant difference in the 12-mg treatment group. Mean times to hospital discharge written order were about 13 hours and 20 hours sooner for the 6-mg and 12-mg treatment groups, respectively, compared to placebo.
Entereg was well tolerated with nausea, vomiting and hypotension observed in all groups, including placebo.
An earlier Phase III, known as Study 302, also hit its primary endpoint of time to recovery in GI function. It was release of that data in April that pushed the company's stock 31 percent north. Study 302 evaluated 450 patients who were scheduled to undergo partial colectomies, simple or radical hysterectomies and to receive opioid analgesics.
Meanwhile, the partners expect to report results on Study 306 during the fourth quarter. That multicenter study is designed primarily to assess the safety of Entereg in postoperative ileus in roughly 500 patients undergoing simple hysterectomies. Accrual is complete.
The final trial, Study 308, is similar to 302 and 313, and is expected to be fully enrolled at 660 patients in the fourth quarter.
Adolor's deal with GSK, of London, is potentially worth $270 million, Peacock told BioWorld Today. On signing the agreement in April 2002, GSK paid an up-front fee of $50 million. The remaining $220 million in milestones are based on filings and approvals in different markets and in different indications. While Peacock said the next milestone would be achieved when the companies file for FDA approval, he would not disclose the amount.