Protease Inhibitor Boceprevir Demonstrates Durable Sustained Response
with No Late Relapse
Genotype 1 chronic hepatitis C patients treated with
the Merck/Schering-Plough's investigational NS3 HCV
protease inhibitor boceprevir
plus pegylated interferon (with or without ribavirin)
achieved durable sustained response with no evidence
of viral rebound or adverse events lingering after completion
of therapy, according to a late-breaker poster presented
this week at the 45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010) in
response (SVR) to hepatitis C therapy -- defined as continued
undetectable HCV viral load 6 months after completion of treatment
-- is generally considered a "cure," though a small
proportion of patients treated with interferon-based
therapy may experience late viral relapse after this point.
Vierling from St. Luke's Episcopal Hospital in Houston and colleagues
looked at long-term outcomes among participants who received boceprevir
plus pegylated interferon alfa-2b (PegIntron), with or without
ribavirin, in previous Phase 2/3 clinical trials.
researchers analyzed blood samples from 604 patients, including
formerly treatment-naive individuals and those who did not respond
to a prior course of pegylated interferon plus ribavirin, after
up to 3 years post-therapy. Most participants (nearly 90%) were
white and the average was about 50 years.
extended follow-up cohort consisted of 520 participants from the
SPRINT-1 treatment-naive trial, of whom 269 patients achieved
SVR and 104 were treatment failures. Another 357 patients were
from Study PO3659 looking at prior non-responders, of whom 21
achieved SVR and 205 were treatment failures. In addition, 5 patients
were included from another prior non-responder study, PO4887.
RNA was detected using the Roche Taqman assay with a lower limit
of detection of 29 IU/mL and resistance mutations were detected
by population sequencing of the HCV NS3 protease region (codons
the 290 patients who achieved SVR, no cases of late relapse
person was confirmed to have been re-infected with HCV based
on genotype/subtype sequence.
patients (5%) experienced serious adverse events during extended
follow-up, similar to those previously described during initial
total of 18 boceprevir resistance mutations were identified,
others: < 9% each.
with the V36M mutation experienced faster reversion to wild-type
(non-mutated) virus after treatment completion compared to
those with T54S or R155K mutations.
following boceprevir combination therapy was durable up to 2 years
after end of treatment," the study investigators concluded.
"No latent serious adverse events or laboratory abnormalities
related to prior treatment were observed over follow-up period."
resistance mutations to boceprevir declined at different rates,
V36M declined fastest; T54S and R155K declined at similar rates,"
they continued. "Variation in the rate of mutational decline
likely reflects the relative fitness of the mutants."
Liver Therapies/St. Luke's Episcopal Hospital, Houston, T; Merck
Research Laboratories, Kenilworth, NJ; Alamo Medical Research,
San Antonio, TX; Mount Vernon Endoscopy Center, Alexandria, VA;
Henry Ford Hospitals, Detroit, MI; Indianapolis Gastroenterology
Research Foundation, Indianapolis, IN; South Florida Center of
Gastroenterology, Wellington, FL; Liver Specialists of Texas,
Houston, TX; Weill Medical College of Cornell University, New
York, NY; Davis Medical Center, University of California, Sacramento,
C; Liver and Intestinal Research Centre, Vancouver, BC, Canada'
LSU Medical Center; Louisiana State University, Shreveport, Baton
Rouge, LA; Hospital Saint Joseph, Marseill, France; Hospital Vall
d'Hebron, Barcelona, Spain; Digestive Disease Associates, Baltimore,
MD; Kelsey Research Foundation, Houston, TX.
Vierling, R Ralston, EJ Lawitz, and others. Long-term outcomes
following combination treatment with boceprevir plus Peg-Intron/ribavirin
(P/R) in patients with chronic hepatitis C, genotype 1 (CHC-G1).
45th Annual Meeting of the European Association for the Study
of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010.