Efficacy and Safety of Glecaprevir/Pibrentasvir in Patients with HCV Genotype 5 or 6 Infection: The ENDURANCE-5,6 Study

Pooled Resistance Analysis in Patients with Hepatitis C Virus Genotype 1 to 6 Infection Treated with Glecaprevir-Pibrentasvir in Phase 2 and 3 Clinical Trials

“…The glecaprevir/pibrentasvir regimen has received marketing approvals in many countries for the treatment of TN and TE-PRS GT1-, GT2-, GT3-, GT4-, GT5-, or GT6-infected patients for durations of 8 weeks or 12 weeks in patients without cirrhosis or with compensated cirrhosis, respectively. Though the number of GT5- and GT6-infected patients receiving the recommended regimen was low in the phase 2 and 3 studies; high SVR12 rates were demonstrated in the phase 3b study ENDURANCE-56 that enrolled 84 GT5- and GT6-infected patients ( 34 ).…”

Systematic review: epidemiology and response to direct‐acting antiviral therapy in genotype 6 chronic hepatitis C virus infection

“…Four studies of GLE/PIB were all clinical trials and with a total 108 GT6 patients . The duration of treatment was mostly 12 weeks; two studies by Asselah et al allocated patients without cirrhosis to the 8‐week arm . SVR rates associated with GLE/PIB were 100% in most studies, except for the abstract by Asselah et al as one of six patients treated with 12‐week GLE/PIB experienced virologic breakthrough (83.3% SVR12), yielding an overall 98% SVR12 in all four studies.…”

“…The duration of treatment was mostly 12 weeks; two studies by Asselah et al allocated patients without cirrhosis to the 8‐week arm . SVR rates associated with GLE/PIB were 100% in most studies, except for the abstract by Asselah et al as one of six patients treated with 12‐week GLE/PIB experienced virologic breakthrough (83.3% SVR12), yielding an overall 98% SVR12 in all four studies. The patient who experienced on‐treatment virologic failure was a 72‐year‐old white male with cirrhosis, Child A with HCV GT6c‐l who was treatment‐naïve, and adherent to the 12‐week course.…”

“…A LDV/SOF trial by Gane et al found NS5A baseline polymorphism in all GT6 patients but negative in a patient who experienced virologic relapse, who instead, had NS5B variant S282T (polymorphism that is associated with resistance to SOF) detected at the time of relapse. Both NS3 and NS5A RASs were found in a patient who experienced virologic breakthrough in a study by Asselah et al (T93A in NS3 sequence and A156M in NS5A sequence, which were both associated with resistance to PIB and GLE respectively), yet high SVR rates were noted in these trials . Thus, based on the limited data available, baseline RASs seems to be common but minimally impact treatment outcome in GT6 patients.…”

“…In comparison, GT6a was more prevalent and 6c‐l was less prevalent in Vietnam (40.6% had 6a, 8.6% had 6b and 30.9% had 6c‐l) and New Zealand (68% had GT6c‐l in and 32% had GT6a or 6b), which may explain the differences in response to LDV/SOF in these regions . Studies have reported subtypes 6f and 6l that have failed to obtain SVR12 in GLE/PIB and LDV/SOF trials respectively (Table ) . In a robust infectious cell culture experiment, it is suggested that even HCV GT6a can escape from DAA pressure and develop resistance individually to SOF, VEL and PIB .…”