Ivacaftor (18) – Kalydeco®

Cystic fibrosis (CF), combination therapy with tezacaftor/ivacaftor in patients 6 to < 12 years (homozygous for F508del mutation)

Characteristics

Start date 01.12.2020 – Marketing authorisation: 25.11.2020
Resolution 20.05.2021
INN Ivacaftor
Brand name Kalydeco®
Pharm. company Vertex Pharmaceuticals (Ireland) Limited
G-BA Procedure ID D-623
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

In a combination regimen with tezacaftor/ivacaftor tablets for the treatment of adults, adolescents, and children aged 6 to < 12 years with cystic fibrosis (CF) who are homozygous for the F508del mutation.

Subpopulation Indication Comparator
Children with cystic fibrosis aged 6 to < 12 years who are homozygous for the F508del mutation. Lumacaftor/Ivacaftor

Studies and Results

No. of studies
(best subpopulation)
0 (Data not accepted)
Study design
(best subpopulation)
Data not accepted (Dossier: Single-arm + no comparison)

  • Clinical trials
    • To demonstrate the additional benefit of IVA + TEZ/IVA in children aged 6 to < 12 years with cystic fibrosis who are homozygous for the F508del mutation, the pharmaceutical manufacturer submitted the single-arm study VX13-661-113 (hereinafter referred to as Study 113) was submitted by the pharmaceutical company to demonstrate the added benefit of IVA + TEZ/IVA.
    • In addition, the pharmaceutical manufacturer submitted the results of the 8-week RCT VX16-661-115 (IVA + TEZ/IVA vs. placebo; hereinafter referred to as Study 115) and the single-arm extension study VX17-661-116 (hereinafter referred to as Study 116).

Children with cystic fibrosis aged 6 to < 12 years who are homozygous for the F508del mutation

  • For children with cystic fibrosis aged 6 to < 12 years who are homozygous for the F508del mutation, the additional benefit of ivacaftor in combination with tezacaftor/ivacaftor compared with the appropriate comparator therapy is not proven.
  • Consequently, the pharmaceutical manufacturer did not submit any study for this patient population that would have been suitable for assessing the additional benefit of IVA + TEZ/IVA compared with the appropriate comparator therapy.
  • Overall, additional benefit is not proven for patients aged 6 years and over but under 12 years with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene.
  • Overall assessment
    • On balance, additional benefit is not proven for patients aged 6 years or older but under 12 years with cystic fibrosis who are homozygous for the F508del mutation in the CFTR gene.

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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