Sofosbuvir (3) – Sovaldi®

• Clinical trials
  • The pharmaceutical manufacturer presents results from a patient population (n=54) of Study 1112 for patients aged 3 to under 12 years with genotype 2 and 3 infections.
  • This was an open-label, multicentre, single-arm study investigating sofosbuvir in previously treated and treatment-naive children and adolescents aged 3 to 18 years.

Patients with chronic hepatitis C aged 3 to < 12 years, genotypes 2 or 3

• Hint of a non-quantifiable additional benefit.
• Due to the single-arm study design, the certainty of the evidence must be regarded as limited and classified as a hint.
• mortality
  • No deaths were observed in the patient population.
• morbidity
  • A sustained virological response 12 (SVR12) or 24 weeks (SVR24) after the end of treatment was achieved in the patient population of Study 1112 receiving sofosbuvir in 17 out of 18 (94.4%) patients with genotype 2 infection.
  • In the one case of non-response, therapy discontinuation occurred due to an adverse event (see below).
  • In patients with genotype 3 infection, SVR12 and SVR24 were achieved in 36 out of 36 cases.
  • Although only single-arm data are available, it can be assumed with a high degree of certainty that these results cannot be achieved with the appropriate comparator therapy, ‘watchful waiting’.
• quality of life
  • Health-related quality of life was assessed 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 0.4 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
  • One patient with a genotype-2 infection experienced an adverse event that led to therapy discontinuation.
  • The child discontinued treatment on day 3 due to an “abnormal taste of the medication” (PT).
  • One patient with a genotype 3 infection experienced a serious adverse event.
• Overall assessment / Conclusion
  • Given the available data, it is possible – despite the single-arm study design – to infer an additional benefit of sofosbuvir in the population of children aged 3 to under 12 years with genotype 2 or 3 HCV infection.
  • The results in the morbidity category relating to sustained virological response (SVR12 and SVR24) cannot, with a high degree of certainty, be achieved with the appropriate comparator therapy of ‘watchful waiting’.
  • There were no deaths; only one serious adverse event occurred, and one therapy discontinuation due to an adverse event.
  • This provides no hint that the potential for harm from sofosbuvir is greater than that of the appropriate comparator therapy.
  • There are therefore no findings on mortality or side effects that call into question the advantage in terms of morbidity.
  • Nor is it assumed that the partial underdosing (in patients ≥ 35 kg) leads to an underestimation of the result.
  • The available data on health-related quality of life cannot be adequately interpreted.
  • However, due to the lack of comparative data, it is not possible to quantify the extent of the additional benefit in this population.

Courtesy translation only, please refer to the German original.