Sofosbuvir (2) – Sovaldi®

• Clinical trials
  • Study 1112 is an open-label, single-arm study investigating sofosbuvir in pre-treated and treatment-naïve children and adolescents aged 3 to 18 years.

a) Treatment-naive patients with chronic hepatitis C aged 12 to < 18 years, genotypes 2 or 3

• Overall, in the adolescent, treatment-naïve population, there is a hint of a non-quantifiable additional benefit, based on the avoidance of side effects associated with the appropriate comparator therapy.
• Morbidity – sustained virological response (SVR)
  • A sustained virological response 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in study 1112 with SOF in 40 out of 41 (97.6%) treatment-naïve patients.
  • For the endpoint category of morbidity, there is therefore no additional benefit compared with the appropriate comparator therapy.
• Side effects
  • There were no deaths, no serious adverse events, nor any adverse events that led to therapy discontinuation due to adverse events.
  • Taking into account the proof of the adverse effects of treatment with peginterferon—which is both sufficient in studies and described in the summary of product characteristics (SmPC) (in particular weight loss and potentially irreversible growth retardation)—the possibility of an interferon--free therapy lasting 12 or 24 weeks, as opposed to the appropriate comparator therapy containing interferon, is considered relevant in terms of avoiding side effects.
  • Due to the single-arm study design, the certainty of the evidence must be regarded as limited and classified as a hint.
• Conclusion
  • The results from the interim report of the open-label, single-arm study 1112 are available for the assessment of additional benefit in the patient group of treatment-naïve patients with chronic hepatitis C aged 12 to < 18 years with genotype 2 or 3 infection.
  • The results of the single-arm study show that, whilst no relevant advantages in terms of morbidity can be inferred for the endpoint of sustained virological response (SVR12), advantages are evident for the endpoint of adverse events.
  • Due to the single-arm study design, it is not possible to quantify the extent of the additional benefit in the adolescent population.

b) Treatment-experienced patients with chronic hepatitis C aged 12 to < 18 years, genotypes 2 or 3

• Overall, there is a hint of a non-quantifiable additional benefit in the adolescent, treatment-experienced population.
• In patients with genotype 2, this is based on the evidence transfer of the results for adult patients, and in patients with genotype 3, on the data on virological response.
• Morbidity – sustained virological response (SVR)
  • In view of the findings from previous benefit assessments for the indication of chronic hepatitis C, it cannot be assumed that similarly high response rates will be achieved with the appropriate comparator therapy, best supportive care.
  • For the morbidity endpoint category, there is therefore an additional benefit in the adolescent population compared with the appropriate comparator therapy; however, the extent of this benefit cannot be quantified due to the lack of comparative data.
  • Treatment-experienced patients with genotype 2 infection: The pharmaceutical manufacturer has not provided any data for treatment-experienced patients with genotype 2 infection.
  • Nevertheless, conclusions regarding SVR can also be drawn for treatment-experienced patients with genotype 2.
  • The resolution on benefit assessment pursuant to Section 35a of the German Social Code, Book V (SGB V) of 17 July 2014 establishes that sofosbuvir offers a minor additional benefit for treatment-experienced adults (genotype 2) compared with peginterferon plus ribavirin.
  • This finding is based on non-comparative data from the FUSION and VALENCE studies, in which an effect of sofosbuvir plus ribavirin on the SVR12 endpoint was observed at 82.1% and 90%, respectively.
  • It is not to be expected that the appropriate comparator therapy, best supportive care, will achieve response rates in adolescent patients that are as high as those seen in adult patients receiving treatment with sofosbuvir plus ribavirin.
• Side effects
  • Consequently, the endpoint categories of quality of life and side effects do not provide any further hints on which to base a conclusion regarding the additional benefit.
  • Due to the single-arm study design and the small number of patients, the certainty of the findings must be regarded as limited and classified as a hint.
• Conclusion
  • The results from the interim report of the open-label, single-arm study 1112 are available for the assessment of additional benefit in the patient group of treatment-experienced patients with chronic hepatitis C aged 12 to < 18 years infected with genotype 3.
  • The results of the single-arm study show that advantages in terms of morbidity can be inferred for the endpoint of sustained virological response (SVR12).
  • As no treatment-experienced patients infected with genotype 2 were included in study 1112, the derivation of any additional benefit is only possible through evidence transfer.

Courtesy translation only, please refer to the German original.