Early clinical data indicating that ViroPharma Inc. has a first-in-class antiviral that is effective against hepatitis C virus boosted the company's shares by 12.9 percent Tuesday.

Preliminary data from a Phase Ib study of HCV-796 demonstrated antiviral effects across several genotypes of the virus in treatment-na ve adults with the infection.

"We also demonstrated that HCV-796 has additional antiviral effects over and above pegylated interferon," said Colin Broom, the Exton, Pa.-based company's chief scientific officer. "Very importantly also is that the combination shows no evidence of viral rebound or loss of effect as you continue dosing."

ViroPharma's shares (NASDAQ:VPHM) climbed $1.44 Tuesday to close at $12.61.

The Phase Ib was a randomized, double-blind, placebo-controlled study of ascending multiple doses. While the target enrollment for each of four cohorts was 16 subjects, the preliminary data included between nine and 11 patients in each cohort receiving treatment with HCV-796 and pegylated interferon, and 15 total receiving pegylated interferon alone.

Patients received doses of 100 mg, 250 mg, 500 mg or 1,000 mg of HCV-796 or a placebo every 12 hours for 14 days, and pegylated interferon alfa-2b (PEG-Intron; 1.5 ug/kg/dose) on days one and seven.

Across all dose groups, the combination of HCV-796 and pegylated interferon resulted in a mean viral reduction of between 3.3 and 3.5 log10 (99.95 percent to 99.97 percent) after the 14 days, compared with a 1.7 log10 with pegylated interferon alone. There were no dose-limiting toxicities, and while safety data remained blinded, tolerability appeared consistent with that expected from pegylated interferon.

The results not only pleased investors but helped build interest in the company's lead product from a 10-year-old HCV research program, which was partnered in 1999 with Madison, N.J.-based Wyeth.

Analyst Joel Sendek, of New York-based Lazard Capital Markets, said his firm is encouraged by the data, but that a larger, longer trial in both na ve and nonresponder patients is needed. The data, he said, "confirm our previous view that in terms of efficacy, HCV-796 is in mid-range of the drugs in development for HCV."

Broom said the agent is the "only non-nucleoside polymerase inhibitor to have unequivocal antiviral activity in humans," and added that it is the "first-in-class molecule among this type of inhibitor."

Only a handful of other companies are working in the space. Broom knows of at least two protease inhibitors in development, which also are "very promising molecules," as well as two polymerase inhibitors, including HCV-796. "Really, there are very few drugs in development for HCV," he said.

Vertex Pharmaceuticals Inc., of Cambridge, Mass., recently signed a $165 million deal with Janssen Pharmaceutica NV, a unit of New Brunswick, N.J.-based Johnson & Johnson, for its HCV protease inhibitor, VX-950, which is in Phase II development. (See BioWorld Today, July 5, 2006.)

Novartis AG, of Basel, Switzerland, took an option in March to develop Idenix Pharmaceuticals Inc.'s Phase IIb HCV candidate NM283, a polymerase inhibitor. The deal is worth up to $525 million to Cambridge, Mass.-based Idenix. (See BioWorld Today, March 30, 2006.)

And Schering-Plough Corp., of Kenilworth, N.J., also is working on an HCV candidate, SCH 503034, a protease inhibitor in Phase II studies in patients who have failed to respond to combination therapy with pegylated interferon and ribavirin, the current standard of care. PTC Therapeutics Inc., of South Plainfield, N.J., has a preclinical HCV partnership with Schering-Plough.

Broom does not consider the other products as competitors because HCV, like many infections, requires a combination of therapies to make the deepest impact on patients.

"Viruses have this uncanny ability to navigate around the inhibition made by any drug," he told BioWorld Today.

Worldwide, about 170 million people are infected with HCV, a liver disease spread through direct contact with the blood of an infected person. It can cause symptoms such as jaundice, abdominal pain, fatigue and fever.

Pegylated interferon and ribavirin offer a benefit in only half of patients with genotype 1 HCV, the most common strain, because of certain tolerability issues.

"Pegylated interferon is associated with headaches and flu-like symptoms. People feel lousy on it. Not everyone can tolerate it," Broom said, adding that ribavirin is associated with anemia in a large percentage of patients.

According to the Centers for Disease Control and Prevention, there are about 4 million Americans infected with HCV, and 2.7 million of them are chronically infected.

"That's a very large, large market potential," Broom said. "It's a real unmet medical need and with better tolerated therapies, more of those patients will come forward for treatment."

ViroPharma intends to start a Phase II study of HCV-796 in the fourth quarter using a 500-mg, twice-daily dose and evaluating the agent for efficacy and safety.

While the trial will focus on patients with genotype 1 - the strain that infected 64 percent of the Phase Ib trial patients - Broom said that ViroPharma "will not forget" the patients infected with other genotypes as development of HCV-796 continues.

In vitro data recently presented at the 13th International Meeting on Hepatitis C Virus & Related Viruses in Cairns, Australia, supported observations from the clinical studies that HCV-796 is applicable to multiple genotypes of HCV, including genotypes 1a, 1b, 2, 3 and 4, and enhances the antiviral effect of pegylated interferon.

Aside from developing HCV-796, ViroPharma commercializes Vancocin, an oral drug approved to treat antibiotic-associated pseudomembranous colitis caused by Clostridium difficile and enterocolitis caused by Staphylococcus aureus.

The company also is developing maribavir, which recently entered Phase III trials for the prevention of cytomegalovirus in patients undergoing stem cell or bone marrow transplants.