Shares of BioCryst Pharmaceuticals Inc. tumbled more than 30 percent following a Phase II miss with the influenza drug peramivir, despite assurances from company executives that inadequate needle-lengths were to blame.
BioCryst's stock (NASDAQ:BCRX), which traded at 18 times the normal volume Thursday, fell $3.78, or 32 percent, to close at $8.
The Phase II study was designed to test the effects of a single intramuscular injection of peramivir, a neuraminidase inhibitor, in reducing the duration of influenza symptoms in patients testing positive for the flu antigen. Patients were randomized to receive one of two doses of peramivir or placebo. While preliminary results from the 313-patient intent-to-treat population showed some improvement over placebo - the median time to alleviation of symptoms over placebo was 22.9 hours with the 150-mg dose and 21.1 hours with the 300-mg dose - they were not statistically significant.
After a brief review, the company concluded the introduction of a shorter needle in the Phase II trial was responsible for the failure.
An earlier Phase I trial administered the drug via a needle that was one-and-a-half inches long, but investigators switched to a "more patient-friendly" one-inch needle for the Phase II study, BioCryst CEO Jon Stonehouse said during a company conference call. "We now know that the length of the needles really matters," he added. Peramivir is designed to work by "getting in fast, blanketing the virus and hitting the flu hard," but won't be effective if the needle can't get the drug into the muscle.
Using serum creatine kinase (CK) as a marker, BioCryst identified 101 patients from the trial who had adequate intramuscular injections. For that group, peramivir showed a more pronounced effect, with an improvement of 64.8 hours, or 2.6 days, over placebo at the 300-mg dose and 44.6 hours over placebo at the 150-mg dose. Stonehouse called those results "impressive," and said that, in comparison, Tamiflu, the flu drug marketed by Basel, Switzerland-based F. Hoffmann-La Roche Ltd., showed improvements of 1.3 days over placebo in a similarly designed study, though the two drugs have not been tested head to head.
BioCryst said those CK-based subset data are compelling enough to take peramivir into large pivotal trials before the end of the year, as planned. "Our aim is to get into position" for the upcoming flu season, Stonehouse said, adding that the problem is "an easy thing to fix, in terms of getting the right needles to the right patients," based on gender and body mass index. The company also plans an additional pharmacokinetic study to start in the coming weeks to look at the effects of different needle lengths and BMI on peramivir.
For some, however, concerns lingered. Analyst Ren Benjamin, of Rodman & Renshaw, questioned during the call whether it was smart for the company to move "right into Phase III" in light of the Phase II results and expressed reservations about the use of the CK marker since elevated levels of that enzyme, which indicate muscle injury, can be caused by a number of things.
BioCryst is developing peramivir, its fast-track drug for both seasonal and life-threatening forms of flu, in part with a four-year, $102.6 million contract from the Department of Health and Human Services. That money is allocated for Phase II and Phase III studies, manufacturing and production process validation and other regulatory requirements.
The company holds all rights to the drug, except in Japan, where peramivir is partnered with Osaka, Japan-based Shionogi & Co., and in Korea, where it's licensed to Green Cross Corp., of South Korea.
In addition to peramivir, Birmingham, Ala.-based BioCryst also has a late-stage cancer drug, Fodosine, which is in Phase III testing in cutaneous T-cell lymphoma.
Fodosine is partnered with Cambridge, UK-based Mundipharma International Holdings Ltd., which is responsible for overseas development.
BioCryst reported a net loss of $7 million, or 24 cents per share, for the second quarter of 2007. As of June 30, the firm had cash of $42.5 million, though it added another $65.3 million in a private placement last month. (See BioWorld Today, Aug. 7, 2007.)