The U.S. Food and Drug Administration (FDA) has always had a reputation for its conservative approach to drug approvals, because it receives much more flack whenever a drug it has approved shows unexpected side effects than it does for delaying potentially helpful new therapies. Yesterday, shares of drug developer Adolor
Adolor first received an approvable letter and call for more clinical data for Entereg back in July 2005. After running another clinical trial to prove the drug's efficacy, Adolor then submitted the additional data in the hopes of getting the drug approved for this indication yesterday, which didn't happen because the FDA is now expressing safety concerns about the drug.
With this most recent approvable letter, the FDA appears to be hung up on two specific safety issues. The agency is first worried about the potential for increased risk of cardiovascular adverse events due to Entereg; it wants to see longer-term data, rather than the interim results presented, from a one-year clinical trial titled Study 14 that Adolor is running with the drug.
The FDA's concern is fair, but it may be unwarranted for several reasons. The drug has been associated with a statistically insignificant increase in these negative cardiovascular events, which only occurred in patients at a high risk for these types of events. And the trial had 800 patients enrolled (not to mention all the other trials), so most adverse events associated with the drug should have been statistically visible. Either way, this trial is expected to be completed near the end of the first quarter next year, with the final data available in the second quarter.
The second reason for the Entereg approvable letter was that the FDA wants a risk management plan in place to control the use of the drug. This is the more worrisome aspect of the letter from a business perspective, as it will limit the off-label usage of Entereg for the much larger opioid-induced bowel dysfunction indication, as well as making it more difficult to prescribe the drug for POI.
Assuming it takes another three months after the completion of Study 14 for Adolor to prepare its approvable letter response, and then that the company receives a six-month class 2 review (which is almost guaranteed, since Adolor will be submitting new data), any sort of FDA thumbs-up or -down on this second approvable letter should not be expected until the first half of 2008. Patient investors may be getting a great discount on shares of Adolor if Study 14 shows no statistical tendencies toward increased risk of heart problems at its completion next year.