An experimental bowel drug from Adolor ( ADLR) and GlaxoSmithKline ( GSK) won't be approved by U.S. regulators next month, despite what seemed like a positive stamp of approval Wednesday from a panel of medical experts. I'm bearish on Adolor, and bullish on Progenics ( PGNX), which has a competing bowel drug with a better chance of success. But here's what happened yesterday: A Food and Drug Administration advisory committee voted 9-6 on Wednesday that the benefits of Adolor's drug Entereg -- reducing by about one day the recovery time and hospital stays for patients undergoing bowel surgery -- outweighed the safety risks of the drug, mainly an increased risk of heart attack. Adolor and partner GlaxoSmithKline seized on this apparent vote of confidence for Entereg, calling it a "favorable" ruling in a press release that helped push Adolor shares higher in Wednesday's after-hours trading session. On Thursday, though, Adolor was down more than 11% to $4.08. The FDA is expected to issue its approval decision for Entereg on Feb. 10. The companies are seeking Entereg's approval as a treatment for post-operative ileus (POI) -- a fancy term that basically means painful bloating and constipation following abdominal surgery. No current drugs are approved to treat POI, but Entereg is a pill designed to block the constipatory effects of pain-killing opioid drugs. The way I see it, the FDA's decision will be negative: Entereg won't be approved, at least not right away. Adolor and its Big Pharma partner will have to provide more data or possibly run a new clinical trial to prove to the FDA that Entereg is not causing patients to have heart attacks or other cardiovascular problems. Entereg isn't a safe drug, at least not yet. I'm not just making that up -- Wednesday's advisory panel said the same thing. By an 8-6 vote, the panel said there was a significant cardiovascular risk associated with short-term Entereg use, which includes the POI indication. Furthermore, the panel said a risk management plan for Entereg, proposed by the companies to mitigate the safety risks of the drug, was woefully inadequate. If the drug were to be approved, the advisory panel said it wanted the FDA to enforce much stricter patient monitoring. Those, to me, were the most important votes from the panel Wednesday. The FDA has all it needs to throw out or disregard the "positive" benefit-to-risk vote of the panel and ask Adolor and Glaxo for more safety data. Regulators don't need much to say no. Heart attack risk is a huge, Texas-sized neon-red flag at the FDA, especially with agency sentiment running strongly in the risk-averse, scaredy-cat direction. (The number of new drug approvals is down and clinical holds on trials for safety concerns are up, in case anyone hasn't noticed.) Remind anyone of what the FDA did to Dendreon ( DNDN) and its prostate cancer drug Provenge? There are shades of similarity, but Adolor is no Dendreon and Entereg is no Provenge. POI isn't life-threatening, and it's a small commercial opportunity -- probably around $200 million tops. Given its partnership with Glaxo, POI isn't worth much more than $3 a share to Adolor at peak -- even if the drug is approved. Adolor has bigger problems, too. The FDA is most definitely concerned about chronic or long-term use of Entereg because of an increased risk of heart attack and cancer. For these reasons, Adolor and Glaxo were forced to halt a clinical trial of Entereg in patients with opioid obstructive disorder (OBD), which requires chronic dosing of the drug to be effective.
This is the significant commercial opportunity, but at this point, it's doubtful Entereg gets there. Without OBD, Glaxo's interest in Entereg will wane. Don't be surprised to see the Big Pharma giant back out of its Adolor partnership.