Tezacaftor / Ivacaftor (3) – Symkevi®

• 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.