US biotechnology group Adolor saw its stock value almost chopped in half yesterday, as a mixed bag of clinical results from two late-stage trials of its key candidate Entereg – which it is developing alongside UK drug major GlaxoSmithKline for opioid-related side effects - caused investors to panic.
Its shares plummeted 45% to close at $13.65, but GSK seemed to shrug off the news, its stock slipping just over 1% to $56.09.
Entereg (alvimopan) - the first in a new class of peripheral mu opioid receptor antagonists – is designed to block the side effects of opioid analgesics, such as morphine, in patients trying to manage chronic pain. Unwanted effects from use of such drugs include constipation, abdominal pain and bloating, and affect around half of all patients taking opioids to tackle moderate to severe pain.
Results from a Phase IIb trial released earlier this year showed that Entereg caused a doubling in spontaneous bowel movements (ie. without resorting to laxatives) compared to placebo, and patients taking the drug also reported improvements on quality-of-life scales.
But results from this latest round of Phase III trials - which were identically designed - are conflicting. A preliminary analysis of the data showed that, while Study 012 met its primary endpoint, with patients achieving a statistically significant improvement in spontaneous bowel movements, Study 013 failed to meet its goal, although it did generate “supportive evidence in a key secondary endpoint of change in average weekly frequency of spontaneous bowel movement,” the groups said.
But Yvonne Greenstreet, Senior Vice President, Research and Development, GlaxoSmithKline, remained upbeat, saying that “the effects on spontaneous bowel movement frequency as well as the overall safety and tolerability are consistent across all the alvimopan studies in this patient population and give a clear indication of potential benefit.”
The companies also reported results from a Phase IIb study of Entereg in cancer patients with opioid-induced bowel dysfunction. The primary endpoint - the change in frequency of spontaneous complete bowel movements, defined as when the patient experiences a feeling of complete evacuation – was not achieved, but there was a clear positive difference in the key secondary endpoint of spontaneous bowel movement frequency consistent with all of the alvimopan OBD studies, the firms said.
GSK and Adolor initially concentrated on developing Entereg for a condition known as post-operative ileus - a transient interruption in bowel motility that is an almost inevitable consequence of abdominal surgery, but suffered a setback last July when US regulators issued an approvable letter requesting more evidence of efficacy.
While the potential market for POI is likely fairly small - in the region of $150 million - approval for managing opioid side effects could be significantly more lucrative, bringing in $500 million-plus by 2010, according to analysts. A filing for the follow-up indication was expected in 2007, though this may be delayed if the companies are forced to carry out another Phase III study to confirm the agent’s efficacy in this setting.