Eight weeks treatment with glecaprevir-pibrentasvir was efficacious and well tolerated in treatment-naive patients with all hepatitis C virus (HCV) genotype infections, with or without cirrhosis, researchers report in a pooled analysis of studies in the October issue of Clinical Gastroenterology and Hepatology.
In a post-hoc analysis of data from 8 trials, comprising more than 2400 patients, Eli Zuckerman et al found that 8-week treatment with glecaprevir-pibrentasvir led to sustained viral response (SVR) rates of 97.6% at 12 weeks in an intent-to-treat population (ITT) and 99.3% in a modified ITT population, regardless of cirrhosis status (see figure).
SVR12 rates were greater than 95% in the modified ITT population, regardless of baseline characteristics, including history of injection drug use, fibrosis score, alcohol use, opioid substitution therapy, or HIV co-infection. In the GTΔ3CC population, rates of SVR12 were high among all subgroups.
The direct-acting antiviral (DAA) combination, also called Mavyret, was approved by the Food and Drug Administration on August 3 for 8 weeks treatment of treatment-naïve patients with chronic HCV genotype 1–6 infection, without cirrhosis or with mild cirrhosis, including patients with moderate to severe kidney disease and those on dialysis. Mavyret was also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both.
The 8 studies included in the analysis were phase 2b, 3a, and 3b clinical trials of patients randomly assigned to groups that received 8 weeks of oral, once-daily glecaprevir-pibrentasvir (300 mg/120 mg). The study populations were included patients with HCV and HIV-1 coinfection, all stages of chronic kidney disease, and a history of injection-drug use.
Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or current alcohol use, opioid substitution therapy, history of injection-drug use, or severe renal impairment. Treatment-emergent adverse events occurred in 58% of patients (headache in 12% and fatigue in 12%). Serious AEs and AEs that led to glecaprevir-pibrentasvir discontinuation were reported in 2% and fewer than 1% of patients, respectively.
The authors state that glecaprevir-pibrentasvir meets the needs of a diverse and changing HCV patient population and might reduce costs of treatment. The short duration of treatment might improve patient adherence, reduce treatment burden, and help reach elimination targets.
With the increasing incidence of infection among young people, especially drug users, the HCV patient population has shifted to treatment-naive individuals without cirrhosis, who more often may be treated in the community setting.
The genotype 1–6 group included 1248 patients in the ITT group (73% without cirrhosis and 27% with compensated cirrhosis; 47% with genotype infection and 22% with genotype 3 infection. The GT∆3CC dataset comprised 1185 patients in the ITT population, with demographic characteristics consistent with those in the genotype 1–6 group.
Tolerability was acceptable, with treatment-emergent adverse events (AEs) occurring in 58% of patients, the most frequent being headache and fatigue (12% each). Serious AEs and those necessitating glecaprevir-pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively.
The authors acknowledged that the post-hoc analysis lacked the statistical power to compare patient groups, and not all studies reported the same data or fully captured data on injection-drug use. A further limitation was the low number of patients in some subgroups — for example, those with recent injection-drug use and those with HCV genotype