Reuters Health Information (2004-11-15): BILN 2061 impressively reduces HCV load but toxicity a concern
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
BILN 2061 (Boehringer Ingelheim) is a potent and specific inhibitor
of HCV NS3 serine protease, a key viral enzyme involved in HCV
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
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
"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.