Washington Editor

Adolor Corp. and partner GlaxoSmithKline plc won U.S. marketing approval late Tuesday of Entereg (alvimopan) to treat postoperative ileus (POI), a condition that causes severe constipation following large- or small-bowel resection surgery.

Regulators followed the recommendations of an FDA advisory panel, which voted 9 to 6 that Entereg's benefits outweigh its risks in short-term use. (See BioWorld Today, Jan. 24, 2008.)

The medication helps hospitalized patients regain normal gastrointestinal function earlier after surgery, which can reduce hospital stays.

About 400,000 patients undergo small- and large-bowel resection surgeries in the U.S. each year. Opioids used for postoperative pain management are a significant contributing factor to POI.

Entereg, an orally administered, peripherally acting mu-opioid receptor antagonist, has been shown to reverse opioid-induced changes in the GI tract without affecting opioid-induced analgesia.

POI imposes considerable additional expense on the health care system, said Adolor CEO Michael R. Dougherty.

"Entereg addresses a compelling unmet medical need and offers a significant advance in the nature of care which may be provided to this patient population," he told investors and analysts Wednesday during a conference call.

The product, the first treatment specifically approved for POI, is the Exton, Pa.-based biotech's first commercial drug, Dougherty said. "It's no small achievement to join the select group of emerging biopharmaceutical companies who have made the transition from a research and development organization to a commercial company and an even more select group of such companies that have earned approval on a new chemical entity," he declared.

Because of concerns about the potential for cardiovascular events, Entereg was approved with a black-box warning and a risk evaluation and mitigation strategy (REMS) - a plan to manage a known or potential serious risk associated with a drug or biological product - which could limit the drug's initial uptake, said analyst Joel Sendek, of Lazard Capital Markets.

Results of a one-year study of Entereg in patients treated with opioid medications for chronic pain showed there were more reports of myocardial infarctions in patients treated with a 0.5-mg dose of Entereg twice daily compared with the placebo group.

However, the FDA noted that the imbalance has not been observed in other studies of Entereg, including studies in patients undergoing bowel resection surgery who took 12 mg twice daily of the drug for up to seven days, the dosage approved by the FDA. "A causal relationship with Entereg and myocardial infarction has not been established," regulators said in a statement.

The REMS program for Entereg requires the drug to be restricted for inpatient hospital use.

Adolor jointly developed Entereg with London-based GSK under a 2002 agreement. However, GSK is developing a lower dose of the drug to treat chronic opioid-induced bowel dysfunction long term in the outpatient setting.

Analyst Leland Gershell, of Cowen & Co., said he expected Entereg to be the "sole player" in the POI market "for the foreseeable future." He pegged the peak U.S. POI opportunity at $150 million.

With an approved product that could provide $75 million in revenue to Adolor and an enterprise value of about $100 million, Gershell predicted the firm's shares to outperform the market by 40 percent over the next 12 months as Entereg is commercialized.

The company's shares (NASDAQ:ADLR) rose 7 percent in morning trading Wednesday, but fell later in the day to close at $5.28, down 9 cents.

Entereg's approval, Sendek said, "effectively eliminates" Tarrytown, N.Y.-based Progenics Pharmaceuticals Inc.'s first-to-market advantage with Relistor, which recently gained U.S. approval to treat opioid-induced constipation in patients with advanced illness receiving palliative care, when response to laxative therapy was not sufficient. (See BioWorld Today, April 28, 2008.)

The Entereg approval, he added, also makes it more difficult for Relistor to establish a presence in POI as potentially second to market and eliminates the unmet medical need.

But analyst Alan Carr, of Needham & Co., said Entereg's restrictions "meaningfully limit the potential for off-label use and ultimately the commercial potential for the drug," which may allow a greater market for Relistor. Both drugs are expected to launch next month, he said in a research note.

Shares of Progenics (NASDAQ:PGNX) were down 33 cents Wednesday, closing at $13.18.