Drug & Device Development

Hepatitis C protease inhibitor reduces viral load

Last Updated: 2003-10-27 8:23:37 -0400 (Reuters Health)

NEW YORK (Reuters Health) - An inhibitor of the NS3 protease of hepatitis C (HCV) demonstrated "exceptional efficacy" in a short-term, proof-of-concept trial in patients infected with HCV genotype 1, investigators report in the October 26th issue of Nature.

After animal testing showed a "low to moderate" oral biological availability, Dr. Daniel Lamarre, with Boehringer Ingelheim (Canada) Ltd, Laval, Quebec, and colleagues tested the agent, BILN2061, in six healthy volunteers.

Over a dose range of 5 to 2400 mg in polyethylene glycol 400 and ethanol (80%:20%), only the highest dose caused nonspecific, relatively mild intestinal adverse events, and no changes in liver function tests were observed.

The investigators next conducted a randomized, double-blind study in patients infected with HCV genotype 1, in whom liver fibrosis was minimal. The 200-mg dose was administered twice daily for two days to eight patients, while two other patients were treated with placebo.

The patients receiving active treatment exhibited 100- to 1000-fold reductions in virus load. In fact, viral load dropped below detectable levels (1500 RNA copies/mL) 24 to 28 hours after administration in two patients, the researchers found. Virus rebound led to a return to pre-treatment levels within 6 to 13 days after starting treatment.

Results were not affected by previous treatment with interferon or liver disease stage. The authors note that this response is significantly greater than that associated with interferon.

"The antiviral results of protease inhibitor BILN 2061 in a proof-of-concept human trial clearly demonstrate the great potential of selective and potent anti-HCV agents," Dr. Lamarre's group maintains.

Although more and longer trials are needed to see if the drug keeps the viral load down and if resistance develops, the scientists believe it "holds great promise to markedly improve treatments of chronic HCV infection."

Nature 2003.

DOI: 10.1038/nature 02099