Adding the HCV protease inhibitor simeprevir (formerly TMC435) to pegylated interferon and ribavirin cured 79% of prior relapsers, and most were eligible to complete treatment after three months, according to findings from the PROMISE study presented at the Digestive Disease Week meeting (DDW 2013) in Orlando.
The advent of direct-acting antiviral agents (DAAs) has ushered in a new era of hepatitis C treatment. While many people with hepatitis C virus (HCV) and providers eagerly anticipate interferon-free regimens, many people with progressive liver disease cannot wait. Adding the first-generation HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivek or Incivo) to pegylated interferon/ribavirin increases response rates, but these drugs have difficult dosing regimens and side-effects of their own. Fortunately, several next-generation DAAs are more effective, easier to take, and better tolerated.
Eric Lawitz from the University of Texas Health Science Center, on behalf of an international team of colleagues, presented findings from PROMISE (TMC435-HPC3007), a Phase 3 trial evaluating the efficacy, safety, and tolerability of simeprevir as an add-on to pegylated interferon/ribavirin for treatment-experienced people with genotype 1 chronic hepatitis C.
An inherited gene which all individuals have. There are three genotypes of IL28B; these influence response to hepatitis C and its treatment. People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. The other two genotypes are known as CT and TT.
- rapid virological response (RVR)
An undetectable hepatitis C RNA viral load within 4 weeks of starting treatment. An extended rapid virological response (eRVR) is when viral load is undetectable within 4 weeks and remains undetectable until at least week 12.
PROMISE enrolled 393 people who previously relapsed after a prior course of interferon-based therapy taken for at least 24 weeks. About 65% were men, most were white, and the median age was 52 years. About 40% had harder-to-treat HCV subtype 1a, about 75% had unfavorable IL28B gene patterns, 15% had advanced liver fibrosis (stage F3), and a similar proportion had cirrhosis (stage F4). People with HIV or hepatitis B co-infection were excluded.
Two-thirds of participants were randomly assigned to receive 150mg once-daily simeprevir plus pegylated interferon alfa-2a (Pegasys) and weight-based ribavirin for 12 weeks, followed by pegylated interferon/ribavirin alone for 12 more weeks. At that point (week 24), using a response-guided therapy algorithm based on response at weeks 4 and 12, they either stopped all treatment or continued interferon/ribavirin through week 48. The control arm received pegylated interferon/ribavirin for 48 weeks, with a placebo during the first 12 weeks.