Disappointing clinical data clobbered shares of two biotech firms Thursday: BioCryst Pharmaceuticals Inc. fell 40.4 percent on news that a Phase III trial of influenza candidate peramivir would be halted for futility, while Catalyst Pharmaceutical Partners lost nearly two-thirds of its value after reporting a Phase IIb miss for cocaine-dependence candidate CPP-109.

For Research Triangle Park, N.C.-based BioCryst, the peramivir blow cost the firm its most advanced program – and one that had been backed by $234.8 million in government funding. Though full analysis from the unblinded study still has yet to be conducted, hopes are not high. Chief Medical Officer William P. Sheridan said it is "unlikely that peramivir development for U.S. registration will continue."

Despite winning approval in Japan and Korea, where it is marketed by partners Shionogi and Co. Ltd. and Green Cross Corp., respectively, the neuraminidase inhibitor has stumbled 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.)

The recommendation to terminate the trial came from the data monitoring committee (DMC) following an analysis that had been intended to recalibrate the sample size, if needed, and instead found that the sample size of 405 patients already had exceeded the predefined futility boundary of 320 subjects.

BioCryst said it shared the DMC's recommendation with the Department of Health and Human Services Biomedical Advanced Research and Development Authority (HHS/BARDA), which has been supporting development of peramivir for seasonal and life-threatening forms of influenza since 2007.

Peramivir is designed to inhibit the interaction of influenza neuraminidase, an enzyme that is critical to the spread of influenza within a host. In contrast to existing neuraminidase inhibitors Relenza (zanamivir, GlaxoSmithKline plc) and Tamiflu (oseltamivir, Roche AG), BioCryst's drug was being positioned to offer more rapid uptake thanks to its intravenous administration and a potential treatment against flu strains that have exhibited resistance to Tamiflu.

In 2009, the 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 were good enough to earn the firm an emergency authorization usage during the swine flu outbreak of 2009 – but the FDA required placebo-controlled trials for full approval. (See BioWorld Today, Oct. 27, 2009.)

The now-suspended trial was designed to test 600 mg of peramivir, administered once daily for five days, in addition to standard of care vs. standard of care alone in adult and adolescent patients who are hospitalized due to serious influenza. Had the study yielded positive data, a new drug application had been expected for 2013.

Shares of BioCryst (NASDAQ:BCRX) lost 99 cents to close Thursday at $1 .46, hitting a 52-week low. Even before the peramivir news, shares had lost all 2012 gains late last month when the company yanked an investigational new drug application for hepatitis C virus (HCV) candidate BCX5191 for safety reasons. The NS5B nucleoside inhibitor became the latest HCV drug caught amid the FDA's safety concerns regarding "nucs," following adverse events reported in trials of New York-based Bristol-Myers Squibb Co.'s nucleotide prodrug BMS-086094. (See BioWorld Today, Aug. 27, 2012.)

That news was compounded by the fact that, only a week earlier, BioCryst had put down stakes in the red-hot HCV space by acquiring Presidio Pharmaceuticals Inc. in an all-stock deal valued at about $101 million, largely to gain rights to two HCV drugs that could complement BCX5191 . (See BioWorld Today, Oct. 19, 2012.)

With peramivir all but out of the picture, at least in the U.S., BioCryst's next most advanced product is gout candidate ulodesine (BCX4208), a purine nucleoside phosphorylate inhibitor. That product wowed in Phase IIb studies last year, and the company has said it intends to pursue a partnership prior to launching Phase III development. (See BioWorld Today, Oct. 16, 2011.)

Elsewhere in the pipeline is BCX4161 for hereditary angioedema, which is set to start a Phase I program before the end of this year.

BioCryst reported a net loss of $9.7 million, or 19 cents per share, in its third-quarter earnings. As of Sept. 30, the firm had about $44 million in cash. Funds from the HHS/BARDA contract, which support Phase II and Phase III testing, along with manufacturing and regulatory requirements, are recognized as revenue and are not included on the company's balance sheet.

Catalyst's CPP-109 Fizzles in Phase IIb

Like BioCryst, Catalyst, of Coral Gables, Fla., has been developing its addiction drug in a government partnership – in this case, working with the National Institute of Drug Abuse (NIDA) – and will work with NIDA to determine the next steps, if any, for CPP-109 (vigabatrin) after a Phase IIb study failed to show that a significantly larger proportion of treated patients were cocaine-free during the last two weeks of the treatment period.

The 24-week placebo-controlled trial enrolled 207 patients to study the rate of cocaine-dependent subjects treated with CPP-109, a GABA analogue, who abstain from cocaine use in the last two weeks of the trial's treatment phase (weeks eight and nine). The drug also failed to hit on other outcome measures, defined as a significantly larger increase in cocaine-negative urine and a significant decrease fraction of use days in medication-treated subjects during weeks three through nine.

It wasn't the first failure for CPP-109 in the tough addiction space. Three years ago, the drug failed in a Phase II study in cocaine-addicted patients, a miss that the company attributed largely to lack of compliance. (See BioWorld Today, June 1, 2009.)

When designing the latest Phase IIb study, funded largely by NIDA, the firm incorporated protocols to ensure maximum compliance, which made Thursday's news particularly discouraging.

Shares of Catalyst (NASDAQ:CPRX) fell 95 cents Thursday, to close at 57 cents.

But, unlike the 2009 failure, at which time CPP-109 was the only drug in Catalyst's pipeline, the company has other programs to fall back on. Patrick J. McEnany, chairman and CEO, said the firm would focus its resources on CPP-115, a GABA aminotransferase inhibitor in Phase I development for infantile spasms, and on recently acquired Firdapse (amifampridine), in development for Lambert-Eaton myasthenic syndrome. Firdapse was sublicensed from Novato, Calif.-based BioMarin Pharmaceutical Inc. late last month.

CPP-109 also is in testing in an investigator-sponsored trial for Tourette's disorder. If data from that study are positive, the company said it could pursue future trials in that orphan indication.

Catalyst has not yet reported its third-quarter earnings. It ended the second quarter with about $7.5 million in cash, though it picked up another $6 million through a public financing in August.