Tezacaftor / Ivacaftor (3) – Symkevi®
Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del)
Characteristics
| Start date | 01.07.2020 – Marketing authorisation: 31.10.2018 |
|---|---|
| Resolution | 17.12.2020 |
| INN | Tezacaftor/Ivacaftor |
| Brand name | Symkevi® |
| Pharm. company | Vertex Pharmaceuticals |
| G-BA Procedure ID | D-553 |
| ATC code | R07AX31 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 | 1 U O |
| Therapeutic area | Metabolic diseases Cystic fibrosis (CF) Orphan (turnover limit) |
| Reason for procedure |
Reassessment: Orphan turnover exceeded
Original resolution: Tezacaftor / Ivacaftor (1) (16.05.2019) |
| Specialty | Bundling |
| Therapeutic indication of the resolution |
|---|
|
Symkevi is indicated in a combination regimen with ivacaftor 150 mg tablets for the treatment of patients with cystic fibrosis (CF) aged 12 years and older who are heterozygous for the F508del mutation and have one of the following mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T. |
| Subpopulation | Indication | Comparator |
|---|---|---|
| Patients 12 years of age and older with cystic fibrosis who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G and 3849+10kbC→T. | Best-Supportive-Care |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (VX14-661-108) |
|---|---|
|
Study design
(best subpopulation) |
H2H vs. ACT (off-label) |
|
Meta analysis
(best subpopulation) |
no |
- Clinical trials
- To assess the additional benefit of TEZ/IVA + IVA in patients aged 12 years and over with cystic fibrosis who are heterozygous for the F508del mutation in the CFTR gene and who have a mutation on the second allele with residual CFTR function (RF mutation) on the second allele, the pharmaceutical manufacturer submitted the Phase III multicentre, randomised, double-blind, placebo-controlled crossover trial VX14-661-108 (hereinafter ‘Study 108’) was submitted by the pharmaceutical company.
Patients aged 12 years and over with cystic fibrosis who are heterozygous for the F508del mutation and carry one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G and 3849+10kbC→T
- An additional benefit is not proven.
- Overall, for patients aged 12 years and over with cystic fibrosis who are heterozygous for the F508del mutation and carry one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G and 3849+10kbC→T; for these patients, therefore, there is no proof that an additional benefit is achieved with treatment using TEZ/IVA + IVA.
- mortality
- The primary endpoint of Study 108 was the ‘absolute change in FEV1%’ (percentage of forced expiratory volume in one second). In addition, endpoints relating to mortality, morbidity, quality of life and side effects were assessed.
- Consequently, the pharmaceutical manufacturer did not submit any study for this patient population that would have been suitable for assessing the additional benefit of tezacaftor/ivacaftor compared with the appropriate comparator therapy.
- morbidity
- The primary endpoint of Study 108 was the ‘absolute change in FEV1%’ (forced expiratory volume in one second). In addition, endpoints relating to mortality, morbidity, quality of life and side effects were assessed.
- This 8-week study (followed by a crossover) is too short to allow for a benefit assessment. Consequently, the pharmaceutical manufacturer did not submit any study for this patient population that would have been suitable for assessing the additional benefit of TEZ/IVA + IVA compared with the appropriate comparator therapy.
- Health-related quality of life
- The primary endpoint of Study 108 was the ‘absolute change in FEV1%’ (percentage of forced expiratory volume in one second). In addition, endpoints relating to mortality, morbidity, quality of life and side effects were assessed.
- Consequently, the pharmaceutical manufacturer did not submit any study for this patient population that would have been suitable for assessing the additional benefit of tezacaftor/ivacaftor compared with the appropriate comparator therapy.
- Side effects
- The primary endpoint of Study 108 was the ‘absolute change in FEV1%’ (forced expiratory volume in one second). In addition, endpoints relating to mortality, morbidity, quality of life and side effects were assessed.
- Consequently, the pharmaceutical manufacturer did not submit any study for this patient population that would have been suitable for assessing the additional benefit of tezacaftor/ivacaftor compared with the appropriate comparator therapy.
Courtesy translation only, please refer to the German original.
Associated procedures
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