The experimental hepatitis C drugs danoprevir and mericitabine, with or without pegylated interferon and ribavirin, showed good safety and efficacy in previously treated patients, according to findings from the MATTERHORN study presented at The Liver Meeting 2012 (the 63rd Annual Meeting of the American Association for the Study of Liver Diseases, or AASLD) this week in Boston. Another analysis from the trial showed good outcomes for people with advanced liver fibrosis.
The advent of direct-acting drugs that target various steps of the hepatitis C virus (HCV) lifecycle have brought about a new era of treatment. Many combination regimens are currently under study, with a focus on difficult-to-treat patients who did not do well on the old standard of care, including non-responders to prior interferon-based therapy and people with advanced liver disease. The ultimate goal is all-oral, interferon-free regimens that are easy to use and cause few side-effects.
Jordan Feld, from Toronto Western Hospital Liver Centre, and colleagues evaluated the safety and efficacy of different regimens containing the second-generation HCV protease inhibitor danoprevir, the nucleoside HCV polymerase inhibitor mericitabine, ribavirin, and for some participants, pegylated interferon. Danoprevir was boosted with a small amount of ritonavir (Norvir) to reach higher levels in the body.
The MATTERHORN study enrolled 379 chronic hepatitis C patients with HCV genotype 1 who were either partial responders (at least a 2 log10 drop in HCV RNA by treatment week 12, but still detectable at the end of treatment) or null responders (less than a 2 log10 drop by week 12) to prior interferon-based treatment.
Approximately 70% of participants were men, most were white and the average age was about 50 years. The study included people with HCV genotypes 1a or 1b, but those with harder-to-treat 1a were not assigned to interferon-free therapy.
About one-quarter of participants had advanced liver fibrosis (equivalent to Metavir stage F3), but all had biopsies or FibroScan measurements showing no cirrhosis. (People with cirrhosis are being studied in a separate trial known as RUSHMORE.) Very few had the favourable IL28B ‘CC’ gene pattern associated with better interferon response.
Prior partial responders were randomly assigned to three treatment arms, all for 24 weeks:
- Interferon-free triple therapy with 100mg twice-daily danoprevir, 1000mg twice-daily mericitabine and 1000-1200mg/day ribavirin;
- Triple therapy with danoprevir, mericitabine and 180mcg once-weekly pegylated interferon alfa-2a (Pegasys);
- Quadruple therapy with all four drugs.
Prior null responders received either interferon-free triple therapy for 24 weeks, the quadruple regimen for 24 weeks or the quadruple regimen with a pegylated interferon/ribavirin ‘tail’ continuing through 48 weeks (the latter group is still undergoing treatment).
Researchers reported rates of sustained virological response, or continued undetectable HCV viral load (