Highlights
- •In Study 661-110 of TEZ/IVA in pwCF and the F508del-CFTR mutation:
- •pwCF aged ≥12 years completed 96 additional weeks of treatment, totaling 216 weeks
- •Improvements in ppFEV1 and PEx were maintained for the additional 96 weeks
- •TEZ/IVA was generally safe and well tolerated
- •
- •TEZ/IVA safety profile was sustained throughout the additional treatment period.
Abstract
Background
Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed
to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants
aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A.
Here we report results from Part B, which evaluated safety and efficacy for an additional
96 weeks.
Methods
Part B enrolled participants aged ≥12 years with CF and F/F or F/RF genotypes who completed TEZ/IVA treatment in either Study 661-110 Part A, Study
661-112 (F/F), or Study 661-114 (F/F). Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination once daily (morning)
and IVA 150 mg once daily (evening) for 96 weeks. Safety endpoints included adverse
events (AEs) and serum liver function tests. Efficacy endpoints included absolute
change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) and pulmonary exacerbation (PEx) rate.
Results
464 participants were enrolled from Part A (n=377) and other eligible studies (n=87);
463 received ≥1 dose of TEZ/IVA. Overall, 92.2% had ≥1 AE, 0.9% had AEs leading to
treatment discontinuation, and 29.4% reported serious AEs. The most common AEs, which
were generally consistent with common manifestations of CF, included infective PEx
of CF, cough, nasopharyngitis, hemoptysis, and headache. Lung function was maintained
over 96 weeks in both genotype groups. PEx rates per year were comparable with Part
A.
Conclusions
TEZ/IVA was generally safe and well tolerated over a further 96 weeks; safety data
were consistent with Part A. Improvements in ppFEV1 and PEx rates were maintained for an additional 96 weeks in Part B.
Keywords
Abbreviations:
AE (adverse event), ALT (alanine aminotransferase), AST (aspartate transaminase), BMI (body mass index), CF (cystic fibrosis), CFTR (cystic fibrosis transmembrane conductance regulator), F/F (homozygous for the F508del-CFTR mutation), F/RF (heterozygous for the F508del-CFTR mutation and a residual function CFTR mutation), IVA (ivacaftor), PEx (pulmonary exacerbations), ppFEV1 (percent predicted forced expiratory volume in 1 second), SD (standard deviation), TEZ (tezacaftor), ULN (upper limit of normal)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: December 27, 2022
Accepted:
December 13,
2022
Received in revised form:
November 29,
2022
Received:
June 15,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
