By Matthew Willett
A small-molecule therapeutic that blocks opioid-induced bowel paralysis without blocking post-operative analgesic performance could speed the recovery of 5 million abdominal surgery patients annually and save billions in health care costs.
Adolor Corp., of Exton, Pa., expects that the Phase III trial of ADL 8-2698 it began enrollment in Monday will form a foundation for approval of the first such drug for post-operative ileus.
The double-blind, placebo-controlled, 180-patient trial will use the same endpoint and design as Phase II studies, but will enroll more patients and evaluate dose dependency through the addition of a higher dose level than a recently completed Phase II trial. Data from that trial showed a 1.3-day improvement in patients' abilities to eat solid food and a two-day improvement in patients' recoveries of intestinal function.
The Phase II data indicated patients were able to leave the hospital 1.4 days earlier with ADL 8-2698 treatment. Adolor said that a decreased hospital stay in the affected patient population could save more than $10 billion annually.
Adolor CEO John Farrar told BioWorld Today another Phase III trial, the second pivotal trial planned for the company's regulatory approval package, will begin mid-year.
"We're projecting enrolling the last patients in these Phase III trials by the end of the year, and having the data shortly thereafter," Farrar said. "We project filing a new drug application by June of next year."
The Phase III trial begun Monday will focus on patients undergoing hysterectomies and colectomies. More than 5 million patients undergo abdominal surgery annually. Farrar said his company is pursuing a co-promotion deal, anticipating the drug's approval.
Farrar said the agent is "like a topical drug inside the gastrointestinal tract." It acts as such because of an inability to cross the blood-brain barrier, acting instead on peripheral opioid receptors in the GI tract. It's that mechanism of action, Farrar said, that could make ADL 8-2698 useful in further indications.
"We'll follow up and initiate a Phase III trial for a second indication later this year in opioid bowel dysfunction," Farrar said. "It's a whole series of symptoms, the most significant being a really serious constipation, a debilitating constipation patients taking opioid narcotics for a protracted period of time get. If patients take opioid narcotics continuously for more than about a couple of weeks there's a significant constipation that doesn't respond well to laxatives or stool softeners. It's a major quality-of-life issue, and we've tested the drug in four Phase II clinical trials, and the drug has worked in every single one."
Adolor also plans to evaluate the compound in combination with a narcotic, creating the first side effect-free narcotic analgesic. Its pipeline also includes topical and systemic compounds that stimulate opioid receptors for corneal surgery pain and itch.
Adolor had $130 million in the bank as of Dec. 31. It raised $90 million in November in its initial public offering, selling 6 million shares at $15 each. (See BioWorld Today, Nov. 15, 2000.)
Adolor's stock (NASDAQ:ADLR) closed unchanged Monday at $17.375. n