Ivacaftor (12) – Kalydeco®

a) Children with cystic fibrosis aged between 6 and < 12 months who have one of the following gating mutations (Class III) in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R

• For children with cystic fibrosis aged between 6 and < 12 months who have one of the following gating mutations (Class III) in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R, there is a hint of a non-quantifiable additional benefit.
• Due to the uncertainty surrounding the extrapolation of the additional benefit to a younger population, there is a hint of a non-quantifiable additional benefit.
• mortality
  • In the study, none of the 124 children aged 6 to < 12 months died whilst receiving treatment with ivacaftor.
• Morbidity – Pulmonary exacerbations
  • Pulmonary exacerbations, particularly those leading to hospital admission, represent a clinically relevant endpoint and are to be regarded as patient-relevant.
  • In Study 124, two different definitions of pulmonary exacerbations were used. Even when both definitions are taken into account, the incidence of pulmonary exacerbations in this age group remains minor.
• Morbidity – Ratio of body weight to height (z-score and percentiles)
  • The infants included in the study already had a weight-for-height ratio at the start of the study that fell within the normal range for the healthy population of the same age and sex (z-score and percentiles).
  • At the end of the study, there were no changes in the weight-for-height ratio compared with baseline. However, it cannot be conclusively assessed to what extent the patients’ increasing age and development influenced the result.
• Morbidity – sweat chloride levels
  • As the extent of the reduction in sweat chloride concentration is not directly associated with the extent of the change in symptoms, this endpoint is not considered to be of direct relevance to patients and is regarded as supplementary.
  • In Study 124, a significant reduction in sweat chloride levels was observed at 24 weeks compared with baseline.
• Health-related quality of life
  • Endpoints in the health-related quality of life category were not investigated in Study 124.
• Side effects
  • Adverse events occurred in 10 patients (90.9 per cent); 3 patients (27.3 per cent) experienced serious adverse events. No patient discontinued treatment with ivacaftor due to adverse events.
• Conclusion
  • Overall, the G-BA concludes that the additional benefit of ivacaftor observed in children and adolescents aged 6 to 11 years and 12 to 18 years to children aged 6 to < 12 months with cystic fibrosis and the following gating mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R, particularly given the comparable clinical presentation, the progressive course of the disease and the limitations in conducting clinical trials in this age group.
  • However, the additional benefit is non-quantifiable, as the current scientific evidence does not permit this at this stage.

Courtesy translation only, please refer to the German original.