GlaxoSmithKline has suffered a setback following the suspension of trials of its new bowel drug Entereg over fears of cardiovascular risk while development partner Adolor Corp’s share price has collapsed on the news.
The blow came after companies announced preliminary data from a Phase III study designed to evaluate the long-term safety and tolerability of Entereg (alvimopan) 0.5 mg twice-daily in patients taking opioids for chronic non-cancer pain and experiencing opioid-induced bowel dysfunction (OBD). Over 800 patients were randomised 2:1 (538 receiving alvimopan and 267 on placebo) and while the proportion of patients experiencing serious adverse events was similar between those treated with alvimopan (13%) and placebo (11%), the firms said that “a numerical imbalance was observed in the number of cardiovascular and neoplasm cases categorised as serious adverse events among alvimopan-treated patients.”
"These unexpected findings are not yet fully understood and require further analyses to ascertain the significance of the data," said Yvonne Greenstreet, senior vice president for R&D at GSK. "We are working to gain a better understanding of these findings, which will help guide our future development."
However, until the results of the study on OBD are fully analysed, GSK has withdrawn a regulatory application for another late-stage trial of Entereg and has also halted a small study, involving 15 patients, for treating OBD in cancer patients receiving strong painkillers. Adolor has suspended enrollment in an Entereg study involving patients taking painkillers after rotator cuff surgery.
The latter’s chief executive, Michael Dougherty, was still upbeat and said that "we continue to believe in the clinical benefit of Entereg and look forward to the further analyses” of these preliminary results. He added that the companies are also continuing to prepare responses to questions raised by the US Food and Drug Administration in November when it granted conditional approval for Entereg as a treatment for post-operative ileus, another type of bowel disorder. Mr Dougherty said the firms’ response is still due to be filed with the agency during the second quarter.
When the FDA expressed its concerns over Entereg last year, shares in Adolor plummeted 44% to $7.69 on the Nasdaq and the latest bit of bad news saw the stock fall 56% to $3.90 in after-close trading.