Ivacaftor (17) – Kalydeco®

Cystic fibrosis (CF), patients from 4 to < 6 months, R117H mutation

Characteristics

Start date 01.12.2020 – Marketing authorisation: 03.11.2020
Resolution 20.05.2021
INN Ivacaftor
Brand name Kalydeco®
Pharm. company Vertex Pharmaceuticals (Ireland) Limited
G-BA Procedure ID D-619
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 0.15 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

Treatment of infants with cystic fibrosis (CF) aged 4 - < 6 months who have an R117H CFTR mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Subpopulation Indication Comparator
Infants with cystic fibrosis aged 4 to < 6 months who have an R117H mutation in the CFTR gene. Best-Supportive-Care

Studies and Results

No. of studies
(best subpopulation)
1 (VX15-770- 124)
Study design
(best subpopulation)
Evidence transfer
Meta analysis
(best subpopulation)
no

  • Clinical trials
    • In the single-arm, open-label Phase III registration trial VX15-770-124, the relevant cohort comprised 7 infants, totalling 6 infants aged 4 to < 6 months.

Infants with cystic fibrosis aged 4 to < 6 months who carry an R117H mutation in the CFTR gene

  • Hint for a non-quantifiable additional benefit
  • Due to the uncertainty arising from the extrapolation of the additional benefit to a younger population, there is a hint of a non-quantifiable additional benefit.
  • Due to the uncertainty surrounding the transfer of the additional benefit to a younger population, a hint is derived overall.
  • Overall assessment / Conclusion
    • On balance, the G-BA concludes that the transferability of the additional benefit of ivacaftor from patients aged 18 years and over to infants with cystic fibrosis aged 4 to < 6 months who carry an R117H mutation in the CFTR gene, is assumed – particularly given the comparable clinical presentation, the progressive course of the disease and the limitations in conducting clinical trials in this age group, whilst taking into account the safety data for children with gating mutations.
    • However, the additional benefit is non-quantifiable, as the current scientific evidence does not permit this at this stage.

Courtesy translation only, please refer to the German original.

Associated procedures

Ivacaftor (27) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and other or unknown mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor 56 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (26) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and RF mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor 21 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (25) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and gating mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor). 28 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (24) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor, 6 to ≤ 11 years (homozygous for F508del mutation) 470 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (23) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor, 6 to ≤ 11 years (heterozygous for F508del and MF mutation) 230 100% Indication of considerable additional benefit Orphan (turnover limit)
Ivacaftor (22) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and others or unknown mutation) 310 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (21) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and RF mutation) 173 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (20) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and gating mutation (incl. R117H)) 133 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (19) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with tezacaftor/ivacaftor in patients 6 to < 12 years (heterozygous for F508del and MF mutation) 50 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (18) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with tezacaftor/ivacaftor in patients 6 to < 12 years (homozygous for F508del mutation) 470 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (17) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), patients from 4 to < 6 months, R117H mutation 1 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (16) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), patients from 4 to < 6 months, gating mutations 1 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (15) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (homozygous for F508del mutation) 2,400 100% Indication of major additional benefit Orphan (turnover limit)
Ivacaftor (14) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and MF mutation) 1,000 100% Hint for major additional benefit Orphan (turnover limit)
Ivacaftor (13) Kalydeco® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), patients ≥ 6 months to < 18 years 26 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (12) Kalydeco® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), ≥ 6 to < 12 months 2 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (11) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), 12 ro < 24 months 5 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (10) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), patients ≥ 18 years with R117H mutation 35–44 100% Hint for minor additional benefit Orphan (turnover limit)
Ivacaftor (9) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), patients from 2 to 5 years 15 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (8) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), various gating mutations, ≥ 6 years 10–11 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (7) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), heterozygous for F508del, ≥ 12 years, combination with tezacaftor 200–300 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (6) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), homozygous for F508del, ≥ 12 years, combination with tezacaftor 2,400 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (5) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), G551D mutation, ≥ 6 years 210 86% Hint for considerable additional benefit Orphan (turnover limit)
Ivacaftor (4) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), ≥ 12 years, combination with tezacaftor n.d. discontinued Orphan
Ivacaftor (3) Kalydeco® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), R117H mutation, 2 to 5 years, > 18 years 0
59
75% minor additional benefit Orphan repealed
Ivacaftor (2) Kalydeco® Vertex Pharmaceuticals Limited Metabolic diseases Cystic fibrosis (CF), various mutations, ≥ 6 years 0
10–11
100% minor additional benefit Orphan repealed
Ivacaftor (1) Kalydeco® Vertex Pharmaceuticals GmbH Metabolic diseases Cystic fibrosis (CF), G551D mutation, ≥ 6 years 0
170
84% considerable additional benefit Orphan repealed


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