Ivacaftor / Tezacaftor / Elexacaftor (17) – Kaftrio®

Cystic fibrosis, combination therapy with ivacaftor, ≥ 2 years, non-Class I mutation (a gating mutation and no F508del mutation)

Characteristics

Start date 01.05.2025 – Marketing authorisation: 04.04.2025
Resolution 16.10.2025
INN Ivacaftor/Tezacaftor/Elexacaftor
Brand name Kaftrio®
Pharm. company Vertex Pharmaceuticals (Germany) GmbH
G-BA Procedure ID D-1195
ATC code R07AX32 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
Therapeutic area Metabolic diseases Orphan (turnover limit)
Reason for procedure New therapeutic indication

Therapeutic indication of the resolution

Ivacaftor/Tezacaftor/Elexacaftor is used as a combination therapy with Ivacaftor for the treatment of cystic fibrosis in patients aged 2 years and over who have a non-Class I mutation, which is a gating mutation and is not an F508del mutation, in the CFTR gene.

Subpopulation Indication Comparator
Erwachsene, Jugendliche und Kinder ab einem Alter von 2 Jahren mit zystischer Fibrose, die mindestens eine Nicht-Klasse-I-Mutation, die eine Gating-Mutation und die keine F508del-Mutation ist, im CFTR-Gen aufweisen

Studies and Results

  • Clinical trials
    • The VX21-445-124 trial is a randomised controlled trial comparing ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor versus placebo, in each case in addition to standard of care.

Adults, adolescents and children aged 2 years and over with cystic fibrosis who have at least one non-Class I mutation, which is a gating mutation and is not an F508del mutation, in the CFTR gene

  • For adults, adolescents and children aged 2 years and over with cystic fibrosis who have at least one non-Class I mutation in the CFTR gene that is a gating mutation and is not an F508del mutation, an additional benefit is not proven.
  • An additional benefit is not proven.
  • There are no direct comparative data available for ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor against the appropriate comparator therapy, ivacaftor.
  • The study VX21-445-124, primarily cited by the pharmaceutical manufacturer, is not suitable for establishing additional benefit.
  • The study is a randomised controlled trial comparing ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor against placebo, in each case in addition to standard of care. No comparison was made against the appropriate comparator therapy, ivacaftor, as determined by the G-BA.
  • The single-arm observational studies cited in support by the pharmaceutical manufacturer (VX22-CFD-016, HEOR-23-445-014, Burgel 2024, Cromwell 2024) and the extension study VX21-445-125 also do not allow for a comparison with the appropriate comparator therapy specified by the G-BA.
  • Consequently, the data submitted by the pharmaceutical manufacturer are not suitable for drawing conclusions regarding the additional benefit of ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.

Associated procedures

Ivacaftor / Tezacaftor / Elexacaftor (17) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination therapy with ivacaftor, ≥ 2 years, non-Class I mutation (a gating mutation and no F508del mutation) 100 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (16) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination therapy with ivacaftor, ≥ 2 years, non-Class I mutation (no F508del mutation and no gating mutation) 375 64% Hint for major additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (11) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination treatment with ivacaftor, from 2 to ≤ 5 years of age (heterozygous for F508del and MF mutation) 160 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (12) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination treatment with ivacaftor, 2 to ≤ 5 years (homozygous for F508del mutation) 250 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (13) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and gating mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 13 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (14) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and RF mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 20 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (15) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and other or unknown mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 33 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (6) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor, from 6 to ≤ 11 years (heterozygous for F508del and MF mutation) 233 100% Indication of considerable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (7) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor, 6 to ≤ 11 years (homozygous for F508del mutation) 470 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (8) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and gating mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor) 28 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (10) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and other or unknown mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor 56 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (9) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and RF mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor 21 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (5) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del and others or unknown mutation). 310 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (4) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del and RF mutation) 173 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (3) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients > 12 years (heterozygous for F508del and gating mutation (incl. R117H)). 133 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (1) Kaftrio® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥12 years (heterozygous for F508del and MF mutation) 1,000 100% Hint for major additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (2) Kaftrio® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (homozygous for F508del mutation) 2,400 100% Indication of major additional benefit Orphan (turnover limit)


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