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) |
| ICD-10 codes (AIS) | E84.0Cystic fibrosis with pulmonary manifestations, E84.1Cystic fibrosis with intestinal manifestations, E84.80, E84.87, E84.88, E84.9Cystic fibrosis, unspecified |
| Alpha-ID codes (AIS) | I129376Neonatal hepatobiliary disease in cystic fibrosis, I130516Cystic fibrosis with other multiple manifestations, I18531Cystic fibrosis, I2487Cystic fibrosis with pulmonary manifestation, I2488Cystic fibrosis with intestinal manifestation, I32495Cystic fibrosis with manifestations in the lungs and digestive tract |
| ORPHAcodes (AIS) | 586Neonatal hepatobiliary disease in cystic fibrosis, 586Cystic fibrosis with other multiple manifestations, 586Cystic fibrosis, 586Cystic fibrosis with pulmonary manifestation, 586Cystic fibrosis with intestinal manifestation, 586Cystic fibrosis with manifestations in the lungs and digestive tract |
| DDD | 0.3 g O |
| Therapeutic area | Metabolic diseases Cystic fibrosis (CF) Orphan (turnover limit) |
| Reason for procedure | New therapeutic indication – Orphan turnover exceeded |
| Specialty | Bundling |
| Therapeutic indication of the resolution |
|---|
|
Kalydeco tablets are used as part of a combination treatment with ivacaftor/tezacaftor/elexacaftor tablets for the treatment of adults, adolescents and children aged and children aged 6 years and older with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene |
| Subpopulation | Indication | Comparator |
|---|---|---|
| Children aged 6 to 11 years with cystic fibrosis who are heterozygous for theF508del mutation in the CFTR gene and carry a mutation with minimal function on the second allele minimal function on the second allele | Best Supportive Care (BSC) |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (VX19-445-116) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT |
|
Meta analysis
(best subpopulation) |
no |
- 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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