Staff Writer

As the 44th annual meeting of the European Association for the Study of the Liver (EASL) swung into high gear Thursday, data from Anadys Pharmaceuticals Inc., Schering-Plough Corp. and Salix Pharmaceuticals Ltd. garnered headlines.

Shares of Anadys plunged more than 40 percent Thursday as investors questioned the safety and partnerability of the company's lead program, the non-nucleoside polymerase inhibitor ANA598.

Just a few months ago, interim data from a Phase Ib study of ANA598 for treatment-naïve HCV patients sent Anadys' stock soaring 115 percent and prompted analysts to call the drug a potential "best-in-class." (See BioWorld Today, Jan. 9, 2009.)

Full data from the randomized, double-blind, placebo-controlled, multiple ascending dose trial - presented at EASL on Thursday - continued to show potent efficacy. Median viral load reduction was 2.4 log10 for the 200-mg group, 2.3 log10 for the 400-mg group and 2.9 log10 for the 800-mg group.

For genotype 1a patients, median reductions were 1.4 log10 at 200 mg, 1.8 log10 at 400 mg and 2.5 log10 at 800 mg - results that Piper Jaffray & Co. analyst Edward Tenthoff wrote in a research note were particularly important given that those patients tend to be less responsive to non-nucleoside polymerase inhibitors.

For genotype 1b patients, median reductions were 2.6 log10 at 200 mg, 2.5 log10 at 400 mg and 3.2 log10 at 800 mg.

Anadys reported that ANA598 was well tolerated in the Phase Ib trial with no serious adverse events. Yet the company also disclosed in its Thursday news release that three out of 24 patients treated in a 14-day healthy volunteer study developed a Grade 2 rash and discontinued treatment.

Analyst Phil Nadeau of Cowen & Co. wrote in a research note that a "12.5 percent rate of rash in two weeks of dosing is worrisome," but he added that the stock's Thursday morning crash indicates investors believe ANA598 will not be successfully developed, which he called an "overinterpretation."

Nadeau reiterated that the EASL data were solid.

In addition to the Phase Ib results, the company presented preclinical data and reconfirmed findings from ongoing long-term toxicity studies. Assuming that all ongoing programs go well, Anadys expects to begin a Phase II study of ANA598 combined with the standard of care by midyear.

Tenthoff predicted that Anadys also will partner ANA598 by midyear. He called the drug the "most desirable HCV polymerase inhibitor in the clinic" - given the recent acquisition of ViroChem Pharma Inc. and its VCH-222 program by Vertex Pharmaceuticals Inc.

Last month, Vertex agreed to buy ViroChem for $377 million in cash and stock. VCH-222, which drove the deal, had shown a 3.7 log10 median viral load decrease in a three-day study of 750-mg twice-daily dosing. (See BioWorld Today, March 5, 2009.)

Shares of San Diego-based Anadys (NASDAQ:ANDS) closed at $3.51 on Thursday, a loss of $2.38, or 40.4 percent.

Schering Presents More Phase II Boceprevir Data

Also on the HCV front at EASL, Schering-Plough Corp. presented final data from its Phase II SPRINT-1 study of boceprevir in treatment-naïve HCV patients.

Boceprevir and Vertex's telaprevir are the most advanced protease inhibitors in development. One or the other is likely to win the race to provide a much-needed and long-anticipated improvement over the HCV standard of care of ribavirin plus pegylated interferon, which often comes under fire for its 40 percent to 50 percent cure rate and significant side effects.

Both boceprevir and telaprevir are in Phase III trials in treatment-naïve and treatment-experienced HCV patients. In the Phase II data comparison game, telaprevir has shown better efficacy in the treatment-experienced setting, while boceprevir appears to have an edge in treatment-naïve patients.

The data from Schering-Plough's 595-patient Phase II treatment-experienced HCV study presented at EASL were similar to interim data seen at last year's annual meeting of the American Association for the Study of Liver Disease.

The study involved treatment with thrice-daily boceprevir along with ribavirin plus pegylated interferon. Patients received either all three drugs for 28 or 48 weeks or a four-week lead-in with ribavirin plus pegylated interferon followed by the addition of boceprevir for 24 or 44 weeks.

For patients receiving the three drugs with no lead-in, 54 percent of those taking the drugs for 28 weeks achieved a sustained virologic response 24 weeks after the end of treatment (SVR24), as did 67 percent of those in the 48-week group. That beats the 38 percent SVR24 seen in the control arm, but data from the lead-in dosing regimen were even better, showing a 56 percent SVR24 for the 28-week group and a 75 percent SVR24 for the 48-week group.

Common adverse events included anemia, which is often associated with ribavirin. Schering-Plough's director of product communications, Bob Consalvo, explained that doctors often decrease the ribavirin dose to control anemia, but new data indicated that may not be the optimal course. Data from a separate arm of the SPRINT-1 study showed that patients on low-dose ribavirin combined with boceprevir and pegylated interferon achieved just a 36 percent SVR24 after 48 weeks of treatment.

"The lesson learned there is you need a full dose of ribavirin," Consalvo said, adding that erythropoietin supplementation appears to be a better option for controlling anemia.

Schering-Plough's shares (NYSE:SGP) rose 22 cents to close at $21.89 on Thursday, while shares of Vertex (NASDAQ:VRTX) dipped 21 cents to close at $26.62.

Salix Hits Endpoints in Phase III Trial

Salix presented data at EASL detailing the results of its Phase III trial with the antibiotic rifaximin for hepatic encephalopathy (HE).

The randomized, double-blind, placebo-controlled, 299-patient study showed that rifaximin reduced the risk of clinical HE breakthrough episodes by 58 percent during the six-month dosing period (p < 0.0001). At six months, breakthrough HE episodes had been experienced by 22 percent of rifaximin-treated patients, compared to 46 percent of placebo-treated patients (p < 0.0001).

The protection against breakthroughs was seen both in the intent-to-treat population and in all subgroups analyzed. Rifaximin's safety profile was comparable to placebo.

Salix first announced the Phase III data from its HE trial last fall and took it to the FDA last December, but the agency asked the company to continue an open-label study to gather 12-month safety data. Salix said it anticipates filing its new drug application for rifaximin in HE this quarter.

The broad-spectrum antibiotic already is marketed in the U.S. for the treatment of traveler's diarrhea, and it generated $79.9 million in revenues last year. Two Phase III trials also are under way for nonconstipation irritable bowel syndrome, and additional studies are focused on prevention of traveler's diarrhea. (See BioWorld Today, July 2, 2008.)

Shares of Raleigh, N.C.-based Salix (NASDAQ:SLXP) rose 47 cents to close at $10.75 Thursday.

In other EASL news:

• Idenix Pharmaceuticals Inc., of Cambridge, Mass., presented data from three HCV programs. IDX184, a nucleotide polymerase inhibitor prodrug in Phase Ib/IIa for HCV, was shown to be well tolerated in healthy volunteers. IDX375, a preclinical non-nucleoside polymerase inhibitor, had bioavailability supportive of once- or twice-daily dosing, limited metabolism, no cytotoxicity and no adverse effects in animal studies. IDX316, a preclinical protease inhibitor, showed potent activity without cytotoxicity in vitro and bioavailability in animals supportive of once- or twice-daily dosing.

Published  April 24, 2009