Adolor’s Entereg gets mixed FDA panel approval

The benefits of Adolor Corp.'s only product, the specialized bowel medicine Entereg, outweighed potential risks, including heart attacks, medical experts said today.

But an advisory panel to the Food and Drug Administration said long-term cardiovascular risks were a major concern, even though the drug developed by Adolor, of Exton, and partner GlaxoSmithKline P.L.C. was effective and reduced hospital recovery time by about a day after abdominal surgery.

The government's assessment is a crucial hurdle for Adolor, which has no marketed products and has worked seven years developing Entereg, also called alvimopan.

Because the assessment was hardly a ringing endorsement, it was unclear whether Adolor and Glaxo would recoup their investment.

"It was definitely a mixed bag," Cowen & Co. analyst Leland Gershell said in an interview after the panel meeting in Silver Spring, Md.

"With all the issues raised on the safety side, and the requirement side, it seems to me that when this drug is approved," Gershell said, "there are going to be so many things weighing on top of it that you are looking at probably a more limited market opportunity."

The next step for Entereg is for the FDA to either approve, reject, or issue an "approvable" letter indicating that the drug may be approved with certain conditions. Those conditions could include a new plan to monitor the use of the drug or more testing in patients. The FDA, which usually follows the recommendations of its advisory committees, is scheduled to consider those options by Feb. 10.

A thumbs-down for the drug would be a major blow for Adolor, which is developing two potential pain medicines in partnership with Pfizer Inc. that are early stage and years away from being marketed.

The committee vote today "is an important milestone for Entereg, and we are pleased with the favorable outcome," said Michael R. Dougherty, president and chief executive officer.

Adolor said it would work with the FDA, including further development of a "risk-management plan" for the drug.

The FDA panel voted, 9-6, that the benefits of Entereg outweighed potential risks, including heart attacks, bone fractures and tumors observed in one longer-term study.

Still, the members also voted almost unanimously - 14 with one abstention - that Adolor's proposed risk-management plan to monitor the drug was inadequate.

Panel members agreed that Entereg helped patients get out of the hospital about a day sooner and was clinically meaningful. But by an 8-6 vote, they also expressed concern about long-term cardiovascular risk.

"It's premature to give you a call on what the regulatory action is going to be at this time," Julie Beitz, director of the FDA's Office of Drug Evaluation, told reporters afterward.

Adolor has proposed Entereg as a treatment for postoperative ileus, a gastrointestinal condition that can occur after abdominal surgery.

In briefing documents released Friday by the FDA, a review team seemed convinced the drug worked, but expressed concern that Entereg not be prescribed outside of hospitals and be given to patients only short-term.

That is because safety issues - including risk of heart attacks - cropped up in longer-term use of Entereg, up to 12 months.

Founded in 1993, Adolor has already received two "approvable" letters for Entereg. But cardiovascular issues emerged last year after a longer opioid-induced-constipation study uncovered serious side effects in patients taking Entereg for six to 12 months. On April 10, after Adolor and Glaxo halted the study, Adolor's stock plunged 59 percent.

Adolor and Glaxo are proposing that Entereg be used by patients up to seven days, and only before and after bowel surgery, to prevent constipation and nausea associated with taking narcotic painkillers, such as morphine.

The companies also proposed a "risk-management plan" that would limit distribution, require wholesalers to sell only to hospitals, and carry product labeling that says "for hospital use only."

Meanwhile, rival Progenics Pharmaceuticals Inc. and partner Wyeth are awaiting an FDA decision April 30 on their competing drug, methynaltrexone, which also treats constipation caused by opioid painkillers. There are currently no approved drugs for the condition.

Trading in Adolor shares was suspended for the day. The shares had closed yesterday unchanged at $4.59 on the Nasdaq.