Ivacaftor (11) – Kalydeco®

Children with cystic fibrosis aged between 12 and < 24 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 12 to < 24 months who have one of the following gating mutations (Class III) in the CFTR gene: G551D, G1244E, G1349D, G178R, G5515, S1251N, S1255P, S549N or S549R, there is a hint of a non-quantifiable additional benefit.
• Due to the uncertainty surrounding the transfer 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 12 to < 24 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 low.
• Morbidity – Body weight-to-height ratio (z-score)
  • In study 124, the change in the z-score for the weight-for-height ratio over 24 weeks was assessed as an endpoint.
  • The weight-for-height ratio is significant for this indication, as developmental disorders and impaired nutrient absorption are among the typical signs of cystic fibrosis.
  • At the end of the study, there were no changes in the z-score for 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
  • Measuring chloride levels in sweat is standard practice as part of the diagnostic process, as these levels reflect the functionality of the CFTR protein, which is the pathophysiological cause of the disease.
  • As the extent of a reduction in sweat chloride concentration is not directly associated with the extent of change in symptoms, this endpoint is not considered to be of immediate 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 18 patients (94.7 per cent); 2 patients (10.5 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 in children and adolescents aged 6 to 11 years and 12 to 18 years to children aged 12 to < 24 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.