Many Genotype 1 Hepatitis C Patients Can Be Cured with 24 Weeks of Telaprevir plus Pegylated Interferon/ribavirin

		SUMMARY: The hepatitis C virus (HCV) NS3/4A protease inhibitor telaprevir used with pegylated interferon and ribavirin produced high sustained response rates among previously untreated HCV genotype 1 chronic hepatitis C patients, and it worked well whether taken 2 or 3 times per day, according to findings from the Study C208 presented last month at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) in Vienna. Researchers at the conference also presented data about telaprevir for people with HCV genotypes 2 or 3 and for treatment-experienced genotype 1 patients.

By Liz Highleyman

Xavier Forns from the University of Barcelona and an international team of colleagues conducted an open-label Phase 2 trial evaluating telaprevir in combination with the standard regimen of pegylated interferon plus ribavirin in people with hard-to-treat HCV genotype 1 who had not received prior interferon-based therapy.

Study C208 included 161 participants in several European countries. About half were men, 90% were white, the mean age was about 45 years, about 20% had advanced fibrosis or cirrhosis, and approximately 80% had high baseline HCV RNA (> 800,000 IU/mL).

Participants were randomly allocated to 4 treatment arms, receiving telaprevir at doses of either 750 mg 3 times daily (every 8 hours) or 1125 mg twice daily (every 12 hours), along with pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (PegIntron) plus weight-adjusted ribavirin. Patients took telaprevir for 12 weeks and then continued pegylated interferon/ribavirin for at least an additional 12 weeks.

In a response-guided design, patients who achieved rapid virological response (RVR) at week 4 and maintained undetectable viral load (< 25 IU/mL) through week 20 stopped treatment at 24 weeks, while those who did not meet these criteria received pegylated interferon/ribavirin for 48 weeks.

The main finding of Study C208 was that 80%-85% of patients across treatment arms achieved sustained virological response (SVR), or undetectable HCV viral load 24 weeks after completing therapy. At EASL the investigators presented data from a sub-analysis of efficacy according to dosing schedule and type of pegylated interferon.

Results

	68% of participants had undetectable HCV RNA from week 4 through 20 and were therefore eligible to stop therapy at 24 weeks.
	18% required treatment for 48 weeks.
	14% discontinued treatment before week 24 due to virological failure, adverse events, or for other reasons.
	Overall, in an intent-to-treat analysis, sustained response rates were high regardless of how often people took telaprevir or which type of pegylated interferon they used:
	Every 8 hours with Pegasys: 85%; Every 8 hours with PegIntron: 81%; Every 12 hours with Pegasys: 83%; Every 12 hours with PegIntron: 82%;
	People who achieved RVR and were treated for 24 weeks did better than those without SVR who were treated for 48 weeks (96% vs 79%, respectively).
	Rates of viral breakthrough during treatment and relapse after treatment completion were low (14 and 9 participants, respectively).
	Rates of adverse event were similar across treatment arms.
	The most common adverse events were skin rash and pruritus (itching).
	8% of participants discontinued therapy due to adverse events, most often rash.

"The majority of patients (68%) qualified to receive 24 weeks of total treatment duration ([due to] undetectable HCV RNA from week 4 through week 20)," the researchers concluded.

"Among these, a high proportion (93%-100%) achieved a SVR, regardless of pegylated interferon type or telaprevir dosing schedule," they added. "Continuing pegylated interferon/ribavirin beyond 24 weeks resulted in high SVR rate in patients that did not meet criteria for shorter treatment."

Liver Unit, University of Barcelona, Barcelona, Spain; Hôpital Beaujon, Clichy, France; Department of Internal Medicine, Medical University of Vienna, Vienna, Austria; Klinikum der Universität zu Köln, Cologne, Germany; Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium; Clinic of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; Radboud University Nijmegen Medical Center, Nijmegen; Netherlands; Hôpital St Antoine, Paris, France; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc, Yardley, PA.

5/14/10

Reference
X Forns, P Marcellin, P Ferenci, and others. On-treatment response-guided therapy with telaprevir q8h or q12h combined with peginterferon alfa-2a or peginterferon alfa-2b and ribavirin in treatment-naive genotype 1 hepatitis C (Study C208). 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract 56).