Ivacaftor (3) – Kalydeco®

• Clinical trials
  • This was an open-label, uncontrolled clinical study investigating the safety and efficacy of two doses of ivacaftor dosages in a total of N = 34 children (50 mg: N = 10; 75 mg: N = 24) aged 2 to 5 years inclusive with a Class III gating mutation on at least one allele.
  • Study 110 is a randomised, placebo-controlled, double-blind, parallel-group Phase III study designed to investigate the efficacy and safety of ivacaftor in patients with CF and an R117H mutation on at least one allele of the CFTR gene.

Children aged 2 to 5 years inclusive with a gating mutation (Class III) in the CFTR gene

• In summary, the extent of the additional benefit of ivacaftor for children with CF aged 2 to 5 years inclusive is assessed as follows:
• There is an additional benefit; however, this is non-quantifiable because the available scientific data do not currently permit this.
• mortality
  • No deaths occurred in the study.
  • With regard to mortality, no conclusion can be drawn from the available results regarding the extent of the additional benefit.
• Morbidity – Body Mass Index (BMI)
  • Both the absolute and the z-score-adjusted changes in BMI showed a statistically significant increase from baseline to week 24.
  • The change relative to the baseline value of 15.98 kg/m² was 0.32 kg/m² (2 %) in absolute terms.
• Morbidity – Pulmonary exacerbations
  • Pulmonary exacerbations, particularly those leading to hospital admission or intravenous antibiotic treatment, represent a clinically relevant endpoint and are considered to be of clinical significance to patients.
  • Pulmonary exacerbations occurred in 15 patients (44.1 %).
  • In these patients, exacerbations were observed for an average of 18.95 days over the 24-week period.
  • The significance of these results cannot be assessed in the absence of a control group.
• Health-related quality of life
  • Quality of life was not assessed in the study.
• Side effects
  • Adverse events (AEs) occurred in almost all patients (97.1%), including 6 serious adverse events (SAEs), of which only 1 SAE was classified as treatment-related.
  • One AE led to withdrawal from the study.
  • The significance of these results cannot be assessed in the absence of a control group.
• Overall assessment
  • In its overall assessment of the available results, the G-BA, based on the marketing authorisation and the desired and adverse effects observed in the aforementioned study, as well as taking into account the comments received, the oral hearing and the severity of the condition, has reached the following assessment of the extent of the additional benefit: there is an additional benefit, but it is non-quantifiable because the current scientific evidence does not permit this at this stage.

Patients aged 18 years and over with an R117H mutation in the CFTR gene

• In summary, the extent of the additional benefit of ivacaftor for patients with CF aged 18 and over who have an R117H mutation in the CFTR gene is assessed as follows:
• There is a minor additional benefit.
• mortality
  • No deaths occurred in the study.
  • With regard to mortality, no conclusion can be drawn from the available results as to the extent of the additional benefit.
• Morbidity – Body Mass Index (BMI)
  • The difference in BMI between the two groups after 24 weeks was not statistically significant.
• Morbidity – Pulmonary exacerbations
  • Pulmonary exacerbations, particularly those leading to hospital admission or intravenous antibiotic treatment, represent a clinically relevant endpoint and are considered to be of relevance to patients.
  • The incidence of pulmonary exacerbations differed slightly in favour of ivacaftor.
  • This difference between the two groups was not statistically significant.
• Morbidity – Lung function (FEV1%)
  • Lung function, measured as FEV1%, changed statistically significantly in favour of the ivacaftor group compared with the baseline value: an increase in the absolute change of 4.51% in the ivacaftor group compared with a decrease in the absolute change of –0.46% in the control group.
  • There are differing views on the clinical relevance of FEV1% for patients.
  • The overall conclusion regarding the extent of the additional benefit remains unaffected by this.
• Health-related quality of life
  • Quality of life was assessed using the validated, disease-specific quality-of-life instrument, the Cystic Fibrosis Questionnaire-Revised (CFQ-R).
  • Ivacaftor therefore provides an additional benefit in terms of health-related quality of life.
• Side effects
  • There was no statistically significant difference between the groups in the number of adverse events (AEs) or serious adverse events (SAEs); no patients experienced therapy discontinuation due to AEs.
  • Based on the results regarding side effects, no conclusion can be drawn regarding additional benefit.
• Overall assessment
  • In accordance with Section 5(7) in conjunction with Section 2(3) of the AM-NutzenV, this represents a previously unattained moderate and not merely minor improvement in treatment-related benefit, as a reduction in disease symptoms and a noticeable improvement in the quality of life for patients is achieved.

Courtesy translation only, please refer to the German original.