Glecaprevir / Pibrentasvir (1) – Maviret®

• Clinical trials
  • The ENDURANCE-I trial is an open-label, randomised, multicentre Phase IIItrial which enrolled 351 treatment-naïve and previously treated adults with chronic HCV genotype 1 infection, with or without HCV-HIV co-infection, and without compensated cirrhosis.
  • The EXPEDITION-I study is a single-arm, open-label, multicentre Phase III study that enrolled treatment-naive or previously treated patients with HCV genotypes 1, 2, 4, 5 or 6 and compensated cirrhosis.
  • The SURVEYOR-I study is an open-label, multicentre, two-part Phase II study that included treatment-naïve and previously treated adult patients with HCV genotypes 1, 4, 5 or 6.
  • The SURVEYOR-II study is a randomised, open-label, multicentre Phase II/IIIstudy, which included treatment-naïve and previously treated adults (aged 18–70 years) with chronic HCV infection of genotypes 2 to 6, with or without compensated cirrhosis.
  • The ENDURANCE III study is a randomised, open-label, actively controlled, multicentre Phase III study that included treatment-naïve adults (aged 18 years or over) with chronic HCV genotype 3 infection without cirrhosis.
  • The CERTAIN-I study is a randomised, open-label, actively controlled and multicentre Phase III study in which DAA-pretreated and DAA-naive Japanese patients with HCV genotype-1, -2 and -3 infection, with or without compensated cirrhosis.
  • The Magellan-II study is a single-arm, open-label, multicentre Phase III study that included treatment-naive and previously treated adults (aged 18 years or over) with chronic HCV infection of genotypes 1 to 6 (genotype 3 in treatment-naïve patients only) who had undergone liver or kidney transplantation and did not have cirrhosis.
  • The EXPEDITION-II study is an open-label, multicentre, two-part Phase III study for treatment-naïve and pre-treated patients with HCV genotypes 1 to 6, with or without compensated cirrhosis, and with HIV co-infection.
  • The CERTAIN-II study is an open-label RCT that included treatment-naïve and treatment-experienced (but DAA-naïve) Japanese patients with chronic hepatitis C of genotype 2 without cirrhosis.

a) Patients without cirrhosis or with compensated cirrhosis and genotype 1

• An additional benefit is not proven.
• For a possible adjusted indirect comparison, the pharmaceutical manufacturer cites the randomised clinical trial CERTAIN-I, which compared glecaprevir/pibrentasvir with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) for research question a) (CHC genotype 1).
• However, the pharmaceutical manufacturer does not identify any studies on appropriate comparator therapy that are suitable for an adjusted indirect comparison via the bridge comparator OBV/PTV/r, and therefore does not present such an indirect comparison.

b1) Patients with genotype 2 – patients without cirrhosis

• The additional benefit is not proven.
• To demonstrate additional benefit for patients with chronic hepatitis C of genotype 2 without cirrhosis, the pharmaceutical manufacturer submits the CERTAIN-II study.
• In the study, glecaprevir/pibrentasvir (300 mg/120 mg once daily), treatment duration 8 weeks (N = 90), with the combination of sofosbuvir and ribavirin (sofosbuvir 400 mg once daily + ribavirin 600–1000 mg twice daily), treatment duration 12 weeks (N = 46).
• The Japanese summary of product characteristics (SmPC) recommends significantly lower doses of ribavirin than the German SmPC. Consequently, the ribavirin dosage (in combination with sofosbuvir) in the CERTAIN-II study differs significantly from the dosage recommendations in the German SmPC.
• According to IQWIG’s estimates, approximately 54% (approx. 25/46) of patients were treated with 400 mg of ribavirin, which is less than specified in the German summary of product characteristics (SmPC) (see table).
• Due to these uncertainties, the CERTAIN-II study is not used for the benefit assessment.
• In summary, there is no proof of additional benefit for patients with chronic hepatitis C without cirrhosis and genotype 2.

b2) Patients with genotype 2 – patients with compensated cirrhosis

• The additional benefit is not proven.

c) Patients without or with compensated cirrhosis and genotype 3

• An additional benefit is not proven.

d) Patients without or with compensated cirrhosis and genotype 4

• The additional benefit is not proven.

e) Patients without cirrhosis or with compensated cirrhosis and genotypes 5 and 6

• The additional benefit is not proven.

f) Patients who have previously been treated with sofosbuvir and ribavirin

• An additional benefit is not proven.

Courtesy translation only, please refer to the German original.