Biocryst Pharmaceuticals Inc. has snatched victory from the jaws of defeat with a new drug application (NDA) filing for intravenous perimavir, a drug that failed a Phase III influenza trial just over a year ago.
At the time, peramivir’s failure tanked Biocryst’s stock by more than 40 percent, but a pre-(NDA) meeting with the FDA in June changed the picture sufficiently to give the drug, a neuraminidase inhibitor in the same class as Tamiflu (olsetamivir, Roche AG) and Relenza (zanamivir, GlaxoSmithKline plc), a second chance.
Peramivir was a hot commodity in 2009 and 2010, when it was authorized for use during the H1N1 pandemic. According to Biocryst’s vice president of investor relations and operations, Robert Bennett, the Centers for Disease Control and Prevention stockpiled about 10,000 courses of the drug, which was used to treat some patients during that season’s pandemic.
Bennett acknowledged that peramivir’s second chance was unusual. “The mechanism is well validated. There have been millions of patients treated with Tamiflu and Relenza.” That history helped both the company and regulators keep faith in the drug. “We’ve always believed that paramivir could be competitive,” Bennett said.
Biocryst’s terminated Phase III trial was designed to test 600 mg of peramivir, once daily for five days, along with standard of care vs. standard of care alone in adult and adolescent patients hospitalized due to serious influenza. (See BioWorld Today, Nov. 12, 2012.)
The drug is approved in Japan and Korea, where it is marketed by Biocryst’s partners Shionogi and Co. Ltd. and Green Cross Corp., respectively, but has had difficulty attaining regulatory approval in the U.S. Inadequate needle length was attributed to the 2007 Phase II failure of an intramuscular version of the drug, which has since been dropped, and BioCryst hit an enrollment delay in its U.S. pivotal program for the current intravenous formulation in early 2011. (See BioWorld Today, Sept. 21, 2007, Nov. 3, 2009, and Jan. 14, 2011.)
In 2009, the Research Triangle Park, N.C.-based firm reported positive Phase III results from two trials in Japan, in which peramivir proved noninferior to Tamiflu. Those data were sufficient for Japanese approval and supported the FDA’s emergency authorization for usage during the swine flu outbreak of 2009, but the FDA requires placebo-controlled trials for full approval. (See BioWorld Today, Oc.t 27, 2009.)
Regarding the failed Phase III trial, Bennett said, “I don’t think it was so much a design flaw, as using a set of endpoints that there wasn’t experience with in the patient setting for hospitalized flu patients. That always introduces some risk. That was the direct guidance we had from the FDA.”
Although the outlook for peramivir looked bleak at that time, the agency told Biocryst that its other clinical data were sufficient for filing an NDA.
“The trial that was conducted in Japan showed difference in timed resolution of symptoms, and we have very extensive safety data from a multitude of trials by our partner and ourselves,” Bennett said.
Bennett added that there will be an advisory panel review, but the company does not yet know the schedule for it. Biocryst is preparing to make peramivir available for the forthcoming flu season beginning in 10 to 12 months.
Biocryst developed peramivir under a $234.8 million contract from the Biomedical Advanced Research and Development Authority. Like other drugs in its class, it inhibits interactions of influenza neuraminidase, a critical enzyme to the spread of influenza in the host. Studies have shown peramivir is active against multiple influenza strains, including H7N9 and pandemic H1N1 swine flu viral strains. Biocryst’s pipeline also includes BCX4161, a kallikrein inhibitor, for hereditary angioedema (HAE), its gout candidate ulodesine and oncology drug forodesine.
Bennett noted that Cinryze (C1 esterase, Viropharma Inc.) is currently the only therapy on the market for HAE prophylaxis. That property attracted a $4.2 billion acquisition offer from London-based Shire plc last month. Shire markets Firazyr (icatibant) for acute attacks of HAE. The disease is estimated to affect 18,000 people in the U.S. and Europe. (See BioWorld Today, Nov. 12. 2013.)
For ulodesine, Biocryst handed in favorable 52-week safety results and evidence of sustained efficacy from the extension phase of its randomized Phase IIb trial of the drug in addition to allopurinol in patients with gout who had failed to reach the serum uric acid therapeutic goal of less than 6 mg/dL on allopurinol alone, as well as positive Phase II safety results in mild to moderate renal impairment. Biocryst is preparing materials and protocols for Phase III trials and is seeking a partner to initiate a pivotal program.
Biocryst discontinued a program in hepatitis C virus (HCV) by withdrawing an investigational new drug application for candidate BCX5191 for safety reasons. The NS5B nucleoside inhibitor was a casualty of FDA housecleaning with regard to safety of “nucs,” after adverse events were reported in trials of New York-based Bristol-Myers Squibb Co.’s BMS-086094. (See BioWorld Today, Aug. 2, 2012.)
The company also recently moved two second-generation kallikrein inhibitors into preclinical development. The second-generation compounds may improve on selectivity and bioavailability of the class, without blood-clotting side effects. Early studies showed similar potency to BCX4161, but better bioavailability.
Shares of Biocryst (NASDAQ:BCRX) closed Friday at $6.92, down 4 cents.