SUMMARY: 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 Vienna.

By Liz Highleyman

Sustained virological 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.

J. 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.

The 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.

The 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.

HCV 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 1-181).

Results

	Among the 290 patients who achieved SVR, no cases of late relapse were confirmed.
	1 person was confirmed to have been re-infected with HCV based on genotype/subtype sequence.
	29 patients (5%) experienced serious adverse events during extended follow-up, similar to those previously described during initial follow-up.
	A total of 18 boceprevir resistance mutations were identified, including:
	R155K, 64%; T54S, 54%; V36M, 54%; T54A, 22%; All others: < 9% each.
	People with the V36M mutation experienced faster reversion to wild-type (non-mutated) virus after treatment completion compared to those with T54S or R155K mutations.

"SVR 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."

"Specific 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."

Advanced 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.

4/16/10

Reference
JM 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. (Abstract).