(185) Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating or residual function mutation

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

James F. Chmiel, MD, MPH, ATSF

Professor of Pediatrics, Chief, Pediatric Pulmonology, Allergy, and Sleep Medicine
Indiana University School of Medicine
Indianapolis, Indiana, United States

Co-Author(s)

PB

Peter J. Barry

United Kingdom
Carla Colombo, MD (she/her/hers)

Professor of Pediatrics
University of Milan, United States
ED

Elke De Wachter

United States
IF

Isabelle Fajac

United States
Marcus A. Mall, MD (he/him/his)

Head of Department
Charité–Universitätsmedizin Berlin
Berlin, Berlin, Germany
Kimberly A. McBennett, MD, PhD

Associate Professor
Case Western Reserve University
Cleveland, Ohio, United States
EM

Edward McKone

United States
PM

Pedro Mondejar-Lopez

United States
Brad Quon

Associate Professor
University of British Columbia and St. Paul’s Hospital
Vancouver, United States
BR

Bonnie W. Ramsey, MD

Professor
University of Washington School of Medicine
Seattle, Washington, United States
PR

Philip Robinson

United States
SS

Sivagurunathan Sutharsan

United States
NA

Neil Ahluwalia

Medical Director
Vertex Pharmaceuticals Incorporated, United States
ML

Mengdi Lu

United States
SM

Samuel Moskowitz

Senior Medical Director
Vertex Pharmaceuticals Incorporated, United States
VP

Valentin Prieto-Centurion

Associate Medical Director
Vertex Pharmaceuticals Incorporated, United States
ST

Simon Tian

United States
DW

David Waltz

VP and Head of CF Clinical Development
Vertex Pharmaceuticals Incorporated, United States
TW

Tanya Weinstock

Associate Medical Director
Vertex Pharmaceuticals Incorporated, United States
FX

Fengjuan Xuan

United States
LZ

Laura Zelazoski

United States
YZ

Yaohua Zhang

Principal Biostatistician
Vertex Pharmaceuticals Incorporated, United States
DP

Deepika Polineni, M.D., M.P.H.

Associate Professor of Medicine
University of Kansas Medical Center, Kansas City, KS, USA, Kansas, United States

Background: The triple combination regimen of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in people with CF aged ≥ 12 years with cystic fibrosis (CF) and heterozygous for F508del-CFTR and either a CFTR gating mutation (F508del-gating genotypes) or residual function mutation (F508del-residual function genotypes). A 96-week Phase 3, open-label extension study was conducted to assess long-term safety and efficacy in these participants.

Methods: Participants received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours. The primary endpoint was safety and tolerability; secondary endpoints included absolute changes in percent predicted FEV₁(ppFEV₁), sweat chloride concentration, body mass index (BMI) and associated z-score, body weight, and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. The annualized rate of change in ppFEV₁ was assessed as a post hoc analysis.

Results: 251 participants (F508del-gating genotypes, n=92; F508del-residual function genotypes, n=159) were enrolled and dosed. The last patient visit will take place on April 8, 2022. Results from primary and secondary endpoints and post hoc analysis will be presented.

Conclusions: Pending

Acknowledgements:

References: