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BioCryst Stock Tanks After Rare Disease Drug’s Phase 2 Failure

Xconomy Raleigh-Durham — 

BioCryst Pharmaceuticals’ strategy to recast itself as a rare disease drug developer hit a stumbling block Monday when the company released results showing that its experimental treatment for a rare genetic disorder failed to work better than a placebo in a mid-stage clinical trial.

The BioCryst (NASDAQ: BCRX) drug, called avoralstat, was developed to treat hereditary angioedema (HAE), a disorder characterized by sudden attacks of inflammation and swelling in the face and lips. When these attacks constrict the airway, the swelling can be fatal. Durham, NC-based BioCryst said Monday that Phase 2 results of testing the liquid-gel form of the drug did not meet the study’s primary goal of reducing the frequency of these swelling attacks.

Investors looked unfavorably on the news, and BioCryst’s stock price plummeted 71 percent to a 52-week low of $1.76 per share.

On a conference call discussing the trial results, BioCryst executives said that the drug’s failure appeared to be related to its formulation as a liquid gel capsule, which was taken three times a day—every eight hours. Chief Medical Officer William Sheridan said that in an earlier trial studying a smaller group of patients, the average time between doses was eight hours; nine hours overnight. But in the larger Phase 2 trial, the overnight interval stretched to 12 hours with some patients. Sheridan said that even though the drug showed a “signal of evidence” of clinical benefit and also suggested that it improved the quality of life in patients, the concentration of the drug in the body over the longer period of time was not enough to pursue further development.

Marc Riedl, clinical director of the Angioedema Center at the University of California, San Diego, said on the call that in his view, the extended time period between doses of the capsule is the best explanation for why the drug failed in the study. “While the studies make every effort to make the patients stick with the compliance of every eight hours, it doesn’t always happen,” he said.

Riedl, who has advised BioCryst and has also received funding from the company for clinical research, said the three times daily dosing doesn’t explain the placebo effect, which he called surprising. But despite the trial results, Riedl said that he believes the BioCryst drug is addressing the correct target.

BioCryst focuses on drugs that affect enzymes involved in disease. The U.S. Hereditary Angioedema Association says that the more than 6,500 Americans who have HAE lack a protein, whose absence can lead to the swelling attacks characteristic of the disorder. The BioCryst drug targets an enzyme called kallikrein, which is formed during an HAE attack. The “overwhelming scientific and clinical evidence” is that kallikrein is the correct target, Riedl said.

BioCryst is now focusing its efforts on a solid pill version of avoralstat. Sheridan said that in animal studies, the duration of the solid dose form of avoralstat’s effect is longer and more sustained than the liquid-gel avoralstat capsules, which means that it might avoid the low levels of the drug seen in the failed Phase 2 study. Sheridan said that studies of the compound in monkeys suggest that the company could develop a pill with at least twice-daily dosing.

“If we can’t get twice-daily dosing, then it’s not a viable proposition,” he said.

The company is also developing what it had been calling its second-generation HAE drug—a version available in a pill that, for now, is called BCX7353. The company has said that although this pill is structurally different than avoralstat, it works similarly to that drug by targeting the kallikrein enzyme. The goal is to develop the compound into a once-daily pill.

In October, the company reported Phase 1 results of BCX7353 showing that the 14 patients in the study met safety objectives needed to support moving the compound into a larger mid-stage study.

BioCryst has secured FDA approval of only one drug—the flu treatment peramivir (Rapivab). Last year, BioCryst sold rights to that drug to CSL Limited (ASX: CSL) for $33.7 million up front. Those rights cover global commercialization of peramivir, except in South Korea, Japan, and Israel, where other companies hold commercialization rights. BioCryst stands to gain up to $12 million more if CSL hits sales targets for the drug.

When BioCryst sold the peramivir rights, the company said it would shift its focus to rare disease drugs. CEO Jon Stonehouse said at the time that selling peramivir rights gave BioCryst additional cash to support rare disease drug research and development. Besides its HAE drug candidate, BioCryst’s pipeline includes BCX4430, which the company is studying as a treatment for hemorrhagic fevers, such as Marburg and Ebola viral infections.

BioCryst has about $100 million in cash and investments, Stonehouse said Monday.

Photo courtesy of Flickr user Steve Smith via a Creative Commons license.