June/July 2017 

Glecaprevir + pibrentasvir (Maviret)—highly effective against genotype 3

Hepatitis C virus (HCV) genotype 3 does not usually respond well to therapy with previously licensed direct-acting antivirals (DAAs). Therapy for this strain of HCV has to be given for up to 24 weeks to ensure a high rate of cure. A highly effective therapy that could be given for shorter duration would therefore fulfill an unmet need, as this could enhance adherence and the willingness of patients to receive treatment.

Glecaprevir + pibrentasvir (G+P) is highly active in vitro against genotype 3 (GT 3) and was tested in a clinical trial called Endurance against a combination of sofosbuvir + daclatasvir in a 12-week course of therapy. An additional arm of this study had an eight-week course of G+P.

Participants were distributed as follows:

  • G+P for 12 weeks – 233 people
  • sofosbuvir + daclatasvir for 12 weeks – 115 people
  • G+P for 8 weeks – 157 people

The average profile of participants who entered the study was as follows:

  • 55% men, 45% women
  • age – 48 years
  • HCV viral load – 6 million IU/mL
  • 64% had a history of injecting street drugs
  • 80% had minimal or no liver fibrosis
  • 99% had genotype 3a


Both 12-week regimens were highly effective with cure rates as follows:

  • G+P – 95%
  • sofosbuvir + daclatasvir – 97%

These differences were not statistically significant and showed that G+P was non-inferior to the other regimen. In other words, G+P was roughly equivalent in effectiveness to the other regimen.

The results for the shortened duration of G +P were remarkable (considering that the duration of therapy was shortened from 12 weeks to eight weeks):

  • 95% cured

This result was statistically non-inferior to the 12-week duration of G+P. In other words, a shorter duration of G+P is more or less equivalent in effectiveness to the longer 12-week course of the same medicines.

In all three regimens the most common reason for virological failure was relapse. That is, the drugs were initially able to suppress levels of HCV in the blood to an undetectable level. However, after the cessation of treatment, virus levels surged.

Adverse events

Serious adverse events were rare in this study, occurring in 2% of participants in each study arm.

Common side effects in all three arms were as follows:

  • headache – 20%
  • nausea – 15%
  • fatigue – 13%

These results are similar to those reported in other clinical trials of emerging therapies for HCV.

Seriously abnormal blood test results were rare, occurring in less than 1% of participants receiving any treatment.

This study shows that the combination of G+P can be very useful for people with HCV genotype 3.

The combination of G+P is expected to be licensed in Canada by the end of the summer of 2017.

—Sean R. Hosein


Foster G, Gane E, Asatryan A, et al. Endurance-3: Safety and efficacy of glecaprevir/pibrentasvir compared to sofosbuvir plus daclatasvir in treatment-naïve HCV genotype-3-infected patients without cirrhosis. In: Programs and abstracts of the International Liver Conference. 13-22 April 2017, Amsterdam, The Netherlands.