Ivacaftor (23) – Kalydeco®
Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor, 6 to ≤ 11 years (heterozygous for F508del and MF mutation)
Characteristics
| Start date | 15.02.2022 – Marketing authorisation: 07.01.2022 |
|---|---|
| Resolution | 04.08.2022 |
| INN | Ivacaftor |
| Brand name | Kalydeco® |
| Pharm. company | Vertex Pharmaceuticals (Germany) GmbH |
| G-BA Procedure ID | D-793 |
| ATC code | R07AX02 Other respiratory system products (R07AX) |
| DDD | 0.3 g O |
| Therapeutic area | Metabolic diseases Orphan (turnover limit) |
| Reason for procedure | New therapeutic indication – Orphan turnover exceeded |
| Specialty | Bundling |
Studies and Results
- Clinical trials
- To assess the additional benefit of IVA/TEZ/ELX + IVA in children aged 6 to 11 years with cystic fibrosis who are heterozygous for the F508del mutation in the CFTR gene and carry a minimal-function mutation on the second allele, the pharmaceutical manufacturer submitted a multicentre, randomised, double-blind, placebo-controlled Phase III trial, VX19-445-116 (hereinafter referred to as Study 116).
Children aged 6 to 11 years with cystic fibrosis who are heterozygous for the F508del mutation in the CFTR gene and carry a minimal-function mutation on the second allele
- mortality
- No deaths occurred in Study 116.
- morbidity
- Pulmonary exacerbations, particularly those leading to hospital admission, represent a clinically relevant endpoint and are to be regarded as patient-relevant.
- For pulmonary exacerbations, there is a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- For serious pulmonary exacerbations, there was no statistically significant difference between IVA/TEZ/ELX + IVA + BSC and placebo + BSC.
- For the respiratory system and gastrointestinal symptoms domains, the patient version shows a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- In addition, the parent/carer version also showed a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC, whilst for the gastrointestinal symptoms domain, no statistically significant difference was observed between the treatment groups.
- Here, a statistically significant difference was observed in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- There are differing views on the clinical relevance of FEV1%. The overall conclusion regarding the extent of the additional benefit remains unaffected by this.
- In Study 116, the absolute change in LCI2.5 after 24 weeks of treatment was measured in comparison with baseline. A statistically significant difference was observed in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- In Study 116, the absolute change in BMI and in the age-adjusted BMI z-score over 24 weeks was assessed as an endpoint. For both endpoints, a statistically significant difference was observed in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- The children included in the study already had a body mass index (BMI) at the start of the study that fell within the normal range for the healthy population of the same age and sex (z-score). However, it cannot be conclusively assessed to what extent the patients’ increasing age and development influenced the results.
- A statistically significant difference was observed in favour of LUM/IVA + BSC compared with placebo + BSC.
- Health-related quality of life
- Health-related quality of life was assessed using the disease-specific, patient-reported CFQ-R (patient version) and encompasses the domains of physical well-being, emotional state, social limitations, body image, eating disorders and treatment burden.
- For the domain of social limitations, the patient version showed a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- For the domains of physical well-being, emotional state, body image, eating disorders and treatment burden, the patient version showed no statistically significant difference between the treatment groups.
- In addition, the parent/carer version also showed a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC for the body image domain.
- Side effects
- No data are available for effect estimates regarding the overall rate of adverse events (AEs).
- For the endpoints SUEs and discontinuation due to AEs, no statistically significant differences were observed between the treatment groups in either case.
- For the endpoint abdominal pain (PT), a statistically significant difference was observed in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- In the category of side effects, there is no statistically significant difference between the treatment arms when viewed as a whole.
- Overall assessment
- For the benefit assessment of IVA/TEZ/ELX + IVA in children aged 6 to 11 years with cystic fibrosis who are heterozygous for the F508del mutation in the CFTR gene and carry a minimal-function mutation on the second allele, the multicentre, randomised, double-blind, placebo-controlled Phase III study 116 was presented in comparison with the appropriate comparator therapy, ‘best supportive care’, as determined by the G-BA. The direct comparison yielded results on mortality, morbidity, quality of life and side effects.
- No deaths occurred in Study 116.
- In the morbidity category, statistically significant differences in favour of IVA/TEZ/EL were observed for the endpoints of pulmonary exacerbations, LCI2.5, BMI and BMI z-score, as well as the ‘respiratory system’ and ‘gastrointestinal symptoms’ domains of the patient version of the CFQ-R, a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- Furthermore, a statistically significant difference in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- No statistically significant difference was observed between the treatment groups for the endpoints of serious pulmonary exacerbations or the additional domain of gastrointestinal symptoms in the parent/carer version of the CFQ-R.
- In the health-related quality of life category, a statistically significant difference was observed in favour of IVA/TEZ/ELX + IVA + BSC compared with placebo + BSC.
- For the domains of physical well-being, emotional state, eating disorders and treatment burden, no statistically significant difference was observed between the treatment groups in either version of the CFQ-R, nor in the additional domains of the parent/carer version—vitality, difficulties at school and subjective health assessment.
- In the ‘side effects’ category, there was no statistically significant difference between the treatment arms when viewed as a whole.
- In summary, for children aged 6 to 11 years with cystic fibrosis who are heterozygous for the F508del mutation in the CFTR gene and carry a minimal-function mutation on the second allele, there is a considerable additional benefit of IVA/TEZ/ELX + IVA compared with the appropriate comparator therapy, BSC.
Courtesy translation only, please refer to the German original.
Associated procedures
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