BioCryst's ($BCRX) stock tanked by 70% last week to around $1.70 after it terminated the liquid-filled soft-gel arm of its clinical program for the treatment of the rare disease hereditary angioedema (HAE), citing problems with, you guessed it, drug delivery. The company will continue to pursue an early-stage solid-dosage formulation of the candidate with its approximately $100 million in cash and investments.
The 74 patients receiving 500 milligrams or 30 milligrams of the Research Triangle Park biotech's avoralstat suffered an average of 0.63 or 0.71 attacks of the disease per week respectively, compared to 0.61 among those on the 36-person placebo arm. The potentially fatal attacks can constrict the airways as a result of swelling of the face and lips.
"OPuS-2 was a well-designed and well executed study that gave us a clear answer regarding the limitations of the liquid gel formulation of avoralstat in a large population of HAE patients. The clear answer is a liquid gel cap of avoralstat given three times a day is not a viable treatment option due to variable drug exposure that drops below the target range when dosed in a diverse clinical setting," CEO Jon Stonehouse told annoyed investors during a conference call.BioCryst CEO Jon Stonehouse
"Our goal is to bring forward a conveniently dosed, highly effective oral drug for HAE patients. This has not changed. Now we will focus all of our attention and our resources to advance both a novel solid dosage form of avoralstat and BCX7353 (a similar candidate that the company hopes can be administered as a once-a-day pill). Both projects will have data readouts this year," he continued.
Compliance issues appear to have contributed to the drug exposure problem. "While the studies make every effort to make the patients stick with the compliance of every eight hours, it doesn't always happen," said Dr. Marc Riedl of the UC San Diego School of Medicine during the call. Some trial patients experienced intervals between dosing of 12 hours overnight, according to Stonehouse.
Chief Medical Officer Dr. William Sheridan said the solid-dosage formulation of avoralstat is showing signs of superior exposure, at least in monkeys. "If we can't get twice daily dosing, then it's not a viable proposition," Riedl said.
In 2014 BioCryst won FDA approval for Rapivab, an intravenous formation of peramivir for acute influenza. In a bid to focus on rare diseases, it in June sold the med's exclusive worldwide commercial rights (excluding Japan, South Korea, Taiwan and Israel) to Australia's CSL for $33.7 million and up to $12 million in milestone payments.
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