PMID- 36581484
OWN - NLM
STAT- MEDLINE
DCOM- 20230614
LR  - 20230614
IS  - 1873-5010 (Electronic)
IS  - 1569-1993 (Linking)
VI  - 22
IP  - 3
DP  - 2023 May
TI  - Long-term tezacaftor/ivacaftor safety and efficacy in people with cystic fibrosis 
      and an F508del-CFTR mutation: 96-week, open-label extension of the EXTEND trial.
PG  - 464-470
LID - S1569-1993(22)01426-6 [pii]
LID - 10.1016/j.jcf.2022.12.006 [doi]
AB  - 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 (ppFEV(1)) 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 ppFEV(1) and PEx rates were maintained for an additional 96 weeks 
      in Part B.
CI  - Copyright (c) 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All 
      rights reserved.
FAU - Flume, Patrick A
AU  - Flume PA
AD  - MUSC Health Cystic Fibrosis Center, Medical University of South Carolina, 96 
      Jonathan Lucas St., Charleston, SC, USA. Electronic address: flumepa@musc.edu.
FAU - Harris, R Scott
AU  - Harris RS
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Paz-Diaz, Hildegarde
AU  - Paz-Diaz H
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Ahluwalia, Neil
AU  - Ahluwalia N
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Higgins, Mark
AU  - Higgins M
AD  - Vertex Pharmaceuticals (Europe) Limited, 2 Kingdom Street, London W2 6BD, UK.
FAU - Campbell, Daniel
AU  - Campbell D
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Berhane, Indrias
AU  - Berhane I
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Shih, Judy L
AU  - Shih JL
AD  - Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, USA.
FAU - Sawicki, Gregory
AU  - Sawicki G
AD  - Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, 300 
      Longwood Avenue, Boston, MA, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
DEP - 20221227
PL  - Netherlands
TA  - J Cyst Fibros
JT  - Journal of cystic fibrosis : official journal of the European Cystic Fibrosis 
      Society
JID - 101128966
RN  - 0 (Aminophenols)
RN  - 0 (Benzodioxoles)
RN  - 0 (CFTR protein, human)
RN  - 0 (Chloride Channel Agonists)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - 1Y740ILL1Z (ivacaftor)
RN  - 0 (tezacaftor)
SB  - IM
MH  - Humans
MH  - Aminophenols/therapeutic use
MH  - Benzodioxoles/therapeutic use
MH  - Chloride Channel Agonists/therapeutic use
MH  - *Cystic Fibrosis/diagnosis/drug therapy/genetics
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/genetics/therapeutic use
MH  - Mutation
OTO - NOTNLM
OT  - Cystic fibrosis
OT  - F508del
OT  - Ivacaftor
OT  - Phase 3
OT  - Tezacaftor
COIS- Declaration of Competing Interests PAF reports grants and personal fees from 
      Vertex Pharmaceuticals outside the submitted work. RSH, HP-D, NA, MH, IB, and JLS 
      are employees of Vertex Pharmaceuticals and may own stock or stock options in 
      Vertex Pharmaceuticals. DC is a former employee of Vertex Pharmaceuticals and 
      owns stock or stock options in Vertex Pharmaceuticals. GS reports personal fees 
      from and advisory boards for Vertex Pharmaceuticals during the conduct of the 
      study, and grants from Vertex Pharmaceuticals and personal fees from Gilead 
      Sciences outside the submitted work.
EDAT- 2022/12/30 06:00
MHDA- 2023/06/12 06:42
CRDT- 2022/12/29 21:53
PHST- 2022/06/15 00:00 [received]
PHST- 2022/11/29 00:00 [revised]
PHST- 2022/12/13 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2022/12/30 06:00 [pubmed]
PHST- 2022/12/29 21:53 [entrez]
AID - S1569-1993(22)01426-6 [pii]
AID - 10.1016/j.jcf.2022.12.006 [doi]
PST - ppublish
SO  - J Cyst Fibros. 2023 May;22(3):464-470. doi: 10.1016/j.jcf.2022.12.006. Epub 2022 
      Dec 27.