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Hepatitis C Drug From Anadys Shows Quick Virus-Killing Punch: potent antiviral activity displayed -2.5 log reduction in 72 hours
  Luke Timmerman 1/8/09
An early peek at data from Anadys Pharmaceuticals (NASDAQ: ANDS) suggests the company may have a promising new drug in the works for hepatitis C. The San Diego-based biotech is announcing results today from the first eight patients with the chronic liver infection, which shows its drug has more viral killing pop in the first three days of treatment than was seen in other drugs studied in its class, with minimal side effects.
The company found that its experimental medicine was able to wipe out 99 percent of the virus from the blood (known as a 2.5 logarithmic reduction) within 72 hours at the lowest dose tested in a Phase I clinical trial, says CEO Steve Worland. This finding was in the first group of patients who took a 200 milligram, twice-daily dose of ANA598. It is just the first slice of data available, and the trial is continuing to enroll patients at two higher doses, Worland says. The company hopes to present full data at the European Association for the Study of the Liver meeting in Copenhagen, Denmark in April.
Today's news will at least give Worland a fresh talking point next week when he meets with a bunch of bummed-out investors at the JP Morgan Healthcare Conference in San Francisco. Worland will try to cheer them up by arguing his company's drug is looking better at this early stage of development than others in its class from Gilead Sciences (NASDAQ: GILD) and Pfizer (NYSE: PFE). Drugs in this class-non-nucleoside polymerase inhibitors-aim to be fast followers in the race to improve treatment for patients with hepatitis C, behind a group of protease inhibitor meds.
Most researchers' attention is now focused on a different class, protease inhibitors like ones from Vertex Pharmaceuticals and Schering-Plough, as well as nucleoside polymerase inhibitors like ones from Pharmasset and Roche. Since the hepatitis C virus is a chronic infection, like HIV, many scientists believe a cocktail of therapies with different viral killing mechanisms is the best way to keep it in check.
"This way you can attack the virus from multiple angles," Worland says.
Anadys (Uh-nad-iss) showed its drug appeared safe in 48 healthy volunteers, at a variety of doses back in November. But of course, it still has a long way to go. The company's plan is to move later this year to a mid-stage clinical trial, which looks at its drug in combination with pegylated interferon alpha and ribavirin, the standard anti-viral course. It's possible Anadys could enroll as many as 100 patients in that trial, and design it to analyze effectiveness for 24 or 48 weeks, although the protocol hasn't been finalized, Worland says. The company is also doing long-term toxicity studies in animals, and working on scaling up manufacturing, he says.
The FDA typically requires companies to first show an ability to quickly wipe out the virus in the first three days, like the study being announced today, before companies can move on to more rigorous long-term follow-up studies, Worland says. Anadys plans to hold a conference call with analysts today at 8:30 am Eastern time to discuss the findings and answer questions about what comes next.
Vertex's chief commercial officer, Kurt Graves, told me his company is looking at emerging polymerase inhibitors
ANA598 Demonstrates Potent Antiviral Activity in an Early Clinical Study in HCV-Infected Patients
Patients treated at the initial dose in an ongoing Phase Ib trial demonstrated a 2.5 log10 median viral load decline after three days

SAN DIEGO, Jan. 8 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced results from the first cohort of an ongoing Phase Ib clinical trial of ANA598, the Company's investigational non-nucleoside polymerase inhibitor. ANA598 was very well-tolerated and demonstrated potent antiviral activity in patients infected with chronic Hepatitis C virus (HCV) in this first cohort of the study.
Patients in the first cohort received 200 mg ANA598 (n=8) or placebo (n=2), twice-daily (bid) for three days. At the end of the treatment period, the median viral load decline was 2.5 log10 (>99%), with a range of 1.4-3.4 log10, for the eight patients who received ANA598. Three patients who received ANA598 were genotype 1a and demonstrated a median viral load decline of 1.6 log10, while five patients who received ANA598 were genotype 1b and demonstrated a median viral load decline of 2.6 log10. All eight patients who received ANA598 demonstrated a rapid decline in viral load, and no patients demonstrated viral rebound while on study drug. In addition to the robust viral load decline, ANA598 was very well-tolerated and there were no serious adverse events in the first dose cohort, although conclusions regarding longer-term safety and tolerability cannot be made until the results of future clinical trials of longer duration in more patients are known. Patients are currently being enrolled in the second cohort (400 mg bid) of the study. Anadys expects to report detailed data from multiple cohorts of the study at an upcoming medical conference.
"We are very pleased with the antiviral activity and safety of ANA598 at this first dose tested in the Phase Ib study," commented James Freddo, M.D., Anadys' Senior Vice President, Drug Development and Chief Medical Officer. "We believe this early data continues to position ANA598 as a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV and we look forward to investigating ANA598 in longer-term studies in combination with current standard of care."
"The clinical and preclinical profile of ANA598 observed to date is very impressive," said Steve Worland, Ph.D., President and CEO of Anadys. "The magnitude of viral load drop reported today for ANA598 is greater than has been reported for any other non-nucleoside HCV inhibitor in a monotherapy study. Furthermore, the rate of initial viral load decline, believed to be associated with direct inhibition of viral replication, is greater than has been reported previously for all classes of HCV polymerase inhibitors, including nucleosides. This demonstrated antiviral potency holds significant promise for the future use of ANA598 in combination with other anti-HCV agents."
About ANA598
Anadys retains worldwide rights to ANA598, which was fully discovered at the Company. Preclinical evaluation of ANA598 was completed in the first quarter of 2008, leading to submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA), subsequent allowance of the IND by the FDA and initiation of clinical investigation in the second quarter of 2008. In December 2008, Anadys announced that the FDA granted fast track designation to ANA598 for the treatment of chronic HCV.
In October 2008, Anadys initiated patient dosing in the Phase Ib study of ANA598 in HCV patients. In the double-blind, randomized placebo-controlled Phase Ib study, treatment-naive genotype 1a and 1b patients are to receive oral capsules of ANA598 over three days at doses of 200 mg bid (twice-a-day), 400 mg bid or 800 mg bid. Ten patients are to be enrolled at each dose level, eight receiving active drug and two receiving placebo.
In a Phase I study in healthy volunteers, ANA598 was administered as capsules at single oral doses of 400 mg, 800 mg, 1400 mg, 2000 mg (fed and fasted) and 3000 mg. In addition, a separate cohort received two 800 mg doses 12 hours apart. ANA598 was well tolerated at all doses and there were no serious adverse events or withdrawals from the study. All reported adverse events were classified as mild or moderate, with no apparent dose relationship. The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 consistent with the potential for once-daily or twice-daily oral dosing.
In the preclinical program, ANA598 was well tolerated at all doses tested in 28-day GLP toxicology studies. In September 2008, Anadys initiated long-term, chronic toxicology studies of ANA598.
If ANA598 is successful in early stage development, the Company anticipates completion of the clinical, toxicology and manufacturing activities required to initiate Phase II studies of ANA598 in combination with current standard of care in mid-2009.
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