Sofosbuvir / Velpatasvir (2) – Epclusa®

• Clinical trials
  • The pharmaceutical manufacturer presents results from a patient population (n=73) of study 1143 for patients aged 6 to under 12 years. This was an open-label, multicentre, single-arm study investigating sofosbuvir/velpatasvir in children and adolescents aged 3 to under 18 years with chronic hepatitis C infection.

a) Patients aged between 6 and < 12 years with chronic hepatitis C (genotypes 1, 4, 5 or 6)

• additional benefit is not proven
• An additional benefit of sofosbuvir/velpatasvir compared with the appropriate comparator therapy is not proven.
• mortality
  • No deaths occurred.
• morbidity
  • A sustained virological response at 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in 68 out of 73 (93.2%) patients in the patient population of 6 to < 12-year-olds in Study 1143 treated with sofosbuvir/velpatasvir.
  • The results of Study 1143 are of the same order of magnitude as those for the appropriate comparator therapies, ledipasvir/sofosbuvir and sofosbuvir plus ribavirin, respectively.
  • For ledipasvir/sofosbuvir, SVR12 and SVR24 rates of 95–100% were observed (see the G-BA resolution of 21 January 2021).
• Health-related quality of life
  • Health-related quality of life was assessed in Study 1143 using the PedsQL 4.0 SF15 (Pediatric Quality of Life Inventory 4.0 Short Form 15) at the start of the study and 24 weeks after the end of treatment.
  • For the entire patient population, this resulted in a change of 4.2 points in the total score over the course of the study.
  • Due to the lack of comparative data, the results cannot be adequately interpreted.
• Side effects
  • In Study 1143, there were two serious adverse events and two discontinuations due to adverse events in each group.
• Overall assessment / Conclusion
  • The single-arm Study 1143 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.
  • A sustained virological response at 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in 68 out of 73 (93.2%) patients in the patient population of 6 to < 12-year-olds in Study 1143 treated with sofosbuvir/velpatasvir. The results of Study 1143 are of the same order of magnitude as those for the appropriate comparator therapies, ledipasvir/sofosbuvir and sofosbuvir plus ribavirin, respectively.
  • There were no deaths, and only two serious adverse events and two adverse events leading to therapy discontinuation due to adverse events occurred. The available data on health-related quality of life are insufficient to allow for interpretation.
  • Overall, no additional benefit can be inferred on the basis of the data presented.

b) Patients aged between 6 and < 12 years with chronic hepatitis C (genotypes 2 or 3)

• additional benefit is not proven
• An additional benefit of sofosbuvir/velpatasvir compared with the appropriate comparator therapy is not proven.
• mortality
  • No deaths occurred.
• morbidity
  • A sustained virological response at 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in 68 out of 73 (93.2%) patients in the patient population of 6 to < 12-year-olds in Study 1143 treated with sofosbuvir/velpatasvir.
  • The results of Study 1143 are of the same order of magnitude as those for the appropriate comparator therapies, ledipasvir/sofosbuvir and sofosbuvir plus ribavirin, respectively.
  • For sofosbuvir plus ribavirin, SVR12 and SVR24 rates of 94.4–100% were observed (see the G-BA resolution of 21 January 2021).
• Health-related quality of life
  • Health-related quality of life was assessed in Study 1143 using the PedsQL 4.0 SF15 (Pediatric Quality of Life Inventory 4.0 Short Form 15) at the start of the study and 24 weeks after the end of treatment.
  • For the entire patient population, this resulted in a change of 4.2 points in the total score over the course of the study.
  • Due to the lack of comparative data, the results cannot be adequately interpreted.
• Side effects
  • In Study 1143, there were two serious adverse events and two discontinuations due to adverse events in each group.
• Overall assessment / Conclusion
  • The single-arm Study 1143 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.
  • A sustained virological response at 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in 68 out of 73 (93.2%) patients in the patient population of 6 to < 12-year-olds in Study 1143 treated with sofosbuvir/velpatasvir. The results of Study 1143 are of the same order of magnitude as those for the appropriate comparator therapies, ledipasvir/sofosbuvir and sofosbuvir plus ribavirin, respectively.
  • There were no deaths, and only two serious adverse events and two adverse events leading to therapy discontinuation due to adverse events occurred. The available data on health-related quality of life are insufficient to allow for interpretation.
  • Overall, no additional benefit can be inferred on the basis of the data presented.

c) Patients aged between 12 and <18 years with chronic hepatitis C (genotypes 1, 4, 5 or 6)

• additional benefit is not proven
• As the pharmaceutical manufacturer has not provided any data for the assessment of the additional benefit of sofosbuvir/velpatasvir compared with the appropriate comparator therapy in adolescents aged between 12 and <18 years with chronic hepatitis C infection, the additional benefit of sofosbuvir/Velpatasvir over and above the appropriate comparator therapy for these patients does not provide proof.

d) Patients aged between 12 and <18 years with chronic hepatitis C (genotypes 2 or 3)

• additional benefit is not proven
• As the pharmaceutical manufacturer has not provided any data for the assessment of the additional benefit of sofosbuvir/velpatasvir compared with the appropriate comparator therapy in adolescents aged between 12 and < 18 years with chronic hepatitis C infection, the additional benefit of sofosbuvir/There is no proof that Velpatasvir is better than the appropriate comparator therapy for these patients.

Courtesy translation only, please refer to the German original.