Drug & Device Development

BILN 2061 impressively reduces HCV load but toxicity a concern

Last Updated: 2004-11-15 10:45:33 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Clinical trial results confirm that short-term oral administration of BILN 2061 significantly reduces hepatitis C virus (HCV) RNA load in patients infected with HCV genotype 1, regardless of the degree of liver fibrosis. However, further clinical trials of BILN 2061 are "on hold pending resolution of animal toxicity issues," investigators note in the November issue of Gastroenterology.

BILN 2061 (Boehringer Ingelheim) is a potent and specific inhibitor of HCV NS3 serine protease, a key viral enzyme involved in HCV replication.

In the three clinical trials reported in the Gastroenterology paper, investigators treated a total of 51 HCV genotype-1-infected patients with 25, 200, or 500 milligrams BILN 2061 twice daily for 2 days. Thirty-one patients had minimal liver fibrosis, 10 had advanced liver fibrosis, and 10 had compensated cirrhosis.

"Viral RNA reductions of 2-3 log10 copies/mL were achieved in most patients," Dr. Holger Hinrichsen from the Institute for Medicine in Kiel, Germany and international colleagues report.

These studies show that BILN 2061 has "impressive antiviral efficacy" in HCV genotype-1-infected patients, Dr. Jean-Michel Pawlotsky from Hopital Henri Mondor in Creteil, France writes in an editorial.

The findings support previously reported "proof-of-concept" studies in which BILN 2061 significantly inhibited HCV replication in vitro and in a small number of HCV-infected patients. (See Reuters Health report October 27, 2003).

The 200-mg and 500-mg doses appeared to be equally effective in the current studies, while the 25-mg dose was somewhat less effective at reducing HCV RNA. Advanced fibrosis or compensated cirrhosis did not alter the antiviral efficacy of BILN 2061.

While BILN 2061 twice daily for 2 days was well tolerated, Dr. Hinrichsen and colleagues note that cardiac toxicity surfaced in recent toxicology studies in animals receiving high doses of BILN 2061 for 4 weeks.

"As a consequence, further trials in humans are pending until further long-term animal studies have established a safe dose for long-term use," they write.

Gastroenterology 2004;127:1347-1355,1629-1632.