8 weeks of <i>Maviret</i> cures 98% of people with hepatitis C and cirrhosis

14 Nov 2018 Keith Alcorn
Originally published on www.infohep.org

An 8-week course of the combination of glecaprevir and pibrentasvir (Maviret) is highly effective in curing hepatitis C in people with compensated cirrhosis, across a wide range of genotypes, Robert S. Brown of Weill Cornell Medical College reported at the AASLD Liver Meeting in San Francisco this week.

Maviret is a highly effective combination of an HCV protease inhibitor (glecaprevir) and an NS5A inhibitor (pibrentasvir) that has been shown to cure hepatitis C in 98% of people without cirrhosis after eight weeks of treatment. A previous study showed that a 12-week course of the combination cured hepatitis C in 99% of people with compensated cirrhosis. The EXPEDITION-8 study was designed to test whether an 8-week treatment course was as effective in previously untreated people with compensated cirrhosis as the rate of cure achieved in the previous 12-week study.

Reducing the duration of treatment to eight weeks saves money and makes it easier for people to adhere to a course of treatment, so all companies developing and marketing drugs for hepatitis C have been striving to show that their products can deliver high rates of cure after eight weeks.

The EXPEDITION-8 study is a non-randomised single-arm study that recruited 270 previously untreated people with hepatitis C of all genotypes apart from genotype 3. Participants were required to have compensated cirrhosis, defined as a liver stiffness measurement greater than 0.75 or Fibroscan measurement less than 14.6 kPa or an APRI score of 2 or above, or biopsy-proven cirrhosis. People with cirrhosis on the borderline of compensation and at higher risk of death (Child-Pugh score above 6) were excluded, as were people with a history of decompensated cirrhosis.

The study protocol was amended midway through the trial to enrol 60 people with genotype 3 infection but results from this group of participants were not included in the analysis presented at The Liver Meeting.

The study population was 60% male, 80% white and had a median age of 60 years. The predominant genotypes were 1a and 1b, accounting for 83% of the study population. Nine per cent had genotype 2 infection, 5% genotype 4 and 3% genotype 6. The study recruited one participant with genotype 5, which is highly concentrated in South Africa and rarely found elsewhere in the world. The median hepatitis C viral load (RNA) was 6.3 log10 IU/ml.

All participants received a glecaprevir and pibrentasvir combination tablet once a day for eight weeks. Intent-to-treat analysis showed that 98% of those who entered the study had a sustained virologic response 12 weeks after the completion of treatment; five people had missing HCV RNA measurements 12 weeks after the completion of treatment but had undetectable HCV RNA at the end of treatment. One participant discontinued treatment before the end of the study. No participants experienced viral rebound after the completion of treatment or viral breakthrough during treatment.

No drug-related serious adverse events were reported during the study. The most frequent adverse events reported in the study were headache, rash, nausea and pruritus (itching), each reported by less than 10% of participants. No laboratory abnormalities were observed in any participant during the study.

The investigators concluded that the study results support the use of an 8-week regimen in all previously untreated people with compensated cirrhosis.