Glecaprevir inhibits HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein and for viral replication. Pibrentasvir targets HCV NS5A, which is essential for viral RNA replication and virion assembly.
Maviret is presented as tablets containing 100mg glecaprevir and 40mg pibrentasvir. The recommended dose for all patients is three tablets given once daily with food.
The recommended duration of treatment is 8 weeks in patients without cirrhosis or 12 weeks in those with cirrhosis. This applies to patients with all genotypes who are naive to hepatitis C therapy and to those with genotypes 1, 2, 4, 5 or 6 who have failed prior therapy with peginterferon + ribavirin ± sofosbuvir, or sofosbuvir + ribavirin. In patients with genotype 3 who have failed prior therapy Maviret treatment should be continued for 16 weeks regardless of whether cirrhosis is present.
The ENDURANCE, SURVEYOR and EXPEDITION clinical trial programmes evaluated the safety and efficacy of glecaprevir/pibrentasvir in patients with genotypes 1 to 6 who were treatment-naive or -experienced with or without cirrhosis. The primary endpoint used in the trials was sustained virologic response at 12 weeks post-treatment (SVR12).
Pooled analysis of data from ENDURANCE-1, -2, 4, SURVEYOR-1, -2, and EXPEDITION-1 and -4 showed that in patients without cirrhosis treated with glecaprevir/pibrentasvir for 8 weeks the rates of SVR12 ranged from 93.5% in genotype 4 patients to 100% in genotype 5 patients. Response rates in patients with genotypes 1, 2 and 6 were 99%, 98% and 90%, respectively.
In patients with cirrhosis treated for 12 weeks the rates of SVR12 were 97% in genotype 1 patients and 100% in patients with genotypes 2, 4, 5 and 6.
Genotype 3 patients
Efficacy of glecaprevir/pibrentasvir in treatment-naive genotype 3 patients without cirrhosis was evaluated in the ENDURANCE-3 study. The rate of SVR12 in the unrandomised 8-week arm of the study was 94.9%. In the 12-week arm, the rate of SVR12 was 95.3% in patients randomised to glecaprevir/pibrentasvir compared with 96.5% in patients randomised to sofosbuvir/daclatasvir.
In addition, in the EXPEDITION-4 study, 100% (11/11) of the genotype 3 infected patients with end-stage renal disease achieved SVR12.
'Maviret is an 8-week, pan-genotypic treatment for non-cirrhotic patients new to treatment with chronic hepatitis C that met all primary efficacy endpoints in its extensive HCV clinical trial program, achieving high cure rates,' said Stefan Zeuzem, M.D., Chief of the Department of Medicine at J.W. Goethe University Hospital in Frankfurt, Germany.
'Maviret offers a new therapy for the majority of HCV patients and removes many complexities of pre-treatment patient evaluation.'
Maviret was well tolerated in clinical trials with headache and fatigue the most commonly reported adverse effects.