Glecaprevir / Pibrentasvir (3) – Maviret®

• Clinical trials
  • This was an open-label, multicentre, single-arm study investigating glecaprevir/pibrentasvir in children and adolescents aged 3 to under 18 years with chronic hepatitis C infection.

a) Children with chronic hepatitis C aged 3 to < 12 years, genotypes 1, 4, 5 or 6

• additional benefit is not proven
• The single-arm study M16-123 (DORA) presented here is not suitable for assessing additional benefit due to the lack of comparison with the appropriate comparator therapy; this would only be possible if there were very large effects compared with the appropriate comparator therapy.
• mortality
  • No deaths occurred
• morbidity
  • A sustained virological response 12 (SVR12) weeks after the end of treatment was achieved in 59 (98.3%) of the children with chronic hepatitis C aged 3 to < 12 years (hepatitis C virus (HCV) genotype 1 or 4).
  • The results from cohorts 2 to 4 of the M16-123 (DORA) are of the same order of magnitude as those for the appropriate comparator therapies ledipasvir/sofosbuvir or sofosbuvir/velpatasvir, or sofosbuvir plus ribavirin or sofosbuvir/velpatasvir.
• Health-related quality of life
  • Health-related quality of life was assessed in the M16-123 (DORA) study using the Paediatric Quality of Life Inventory (PedsQL) at the start of the study and 12 weeks after the end of treatment.
  • For children with HCV genotype 1 or 4, there was a change of -1.12 points in the total score over the course of the study.
  • However, due to the lack of comparative data, the results cannot be interpreted with sufficient certainty.
• Side effects
  • In cohorts 2 to 4 of the M16-123 (DORA) study, children with HCV genotype 1 or 4 experienced treatment discontinuation due to adverse events (1.7%), but no serious adverse events (SAEs) occurred.
• Overall assessment / Conclusion
  • The single-arm study M16-123 (DORA) presented here is not suitable for assessing additional benefit due to the lack of a comparator therapy that is appropriate; this would only be possible if there were very large effects compared with the appropriate comparator therapy.
  • A sustained virological response 12 (SVR12) weeks after the end of treatment was achieved with glecaprivir/pibrentasvir in 98.3% of children with chronic hepatitis C aged 3 to < 12 years (hepatitis C virus (HCV) genotype 1 or 4).
  • The results from cohorts 2 to 4 of the M16-123 (DORA) are of the same order of magnitude as those for the appropriate comparator therapies ledipasvir/sofosbuvir or sofosbuvir/velpatasvir, or sofosbuvir plus ribavirin or sofosbuvir/velpatasvir.
  • The available data on health-related quality of life are insufficient to allow for a meaningful interpretation.
  • Overall, no additional benefit can be inferred on the basis of the data presented.

b) Children with chronic hepatitis C aged 3 to < 12 years, genotype 2 or 3

• additional benefit is not proven
• The single-arm study M16-123 (DORA) submitted is not suitable for assessing additional benefit due to the lack of a comparison with the appropriate comparator therapy; this would only be possible if there were very large effects compared with the appropriate comparator therapy.
• mortality
  • No deaths occurred
• morbidity
  • The results for cohorts 2 to 4 of the M16-123 (DORA) are of the same order of magnitude as those for the appropriate comparator therapy of ledipasvir/sofosbuvir or sofosbuvir/velpatasvir, or sofosbuvir plus ribavirin or sofosbuvir/velpatasvir.
  • For sofosbuvir plus ribavirin, SVR12 and SVR24 rates of 94.4–100% were observed (see the G-BA’s resolution of 21 January 2021). It cannot therefore be assumed that there are significant effects compared with the newly defined appropriate comparator therapy.
• Health-related quality of life
  • Health-related quality of life was assessed in the M16-123 (DORA) study using the Paediatric Quality of Life Inventory (PedsQL) at the start of the study and 12 weeks after the end of treatment.
  • For children with HCV genotype 2 or 3, this resulted in a change of -8.66 points in the total score over the course of the study.
  • However, due to the lack of comparative data, the results cannot be adequately interpreted.
• Side effects
  • No serious adverse events (SAEs) or discontinuations due to adverse events occurred in children with HCV genotype 2 or 3.
• Overall assessment / Conclusion
  • The single-arm study M16-123 (DORA) presented here is not suitable for assessing additional benefit due to the lack of comparison with the appropriate comparator therapy; this would only be possible, at best, if there were very large effects compared with the appropriate comparator therapy.
  • The results of cohorts 2 to 4 of the M16-123 (DORA) are of the same order of magnitude as those of the appropriate comparator therapies ledipasvir/sofosbuvir or sofosbuvir/velpatasvir, or sofosbuvir plus ribavirin or sofosbuvir/velpatasvir.
  • The available data on health-related quality of life cannot be adequately interpreted.
  • Overall, no additional benefit can be inferred on the basis of the data presented.

Courtesy translation only, please refer to the German original.