Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor for 24 Weeks or Longer in People with Cystic Fibrosis and One or More F508del Alleles: Interim Results of an Open-Label Phase 3 Clinical Trial
Open accessAbstract
Safety results from this interim analysis were consistent with the initial 24-week placebo-controlled F/MF pivotal study, with similar or lower exposure-adjusted event rates observed in the OLE (Table 1) (5). ELX/TEZ/IVA was generally safe and well tolerated. Most AEs were consistent with common manifestations of CF and were not treatment limiting (3, 10). In participants who received ELX/TEZ/IVA in parent studies, improvements in efficacy and PD measures, including ppFEV1, SwCl concentration, BMI, CFQ-R RD score, and PEx event rate, were maintained or continued to improve further over 24 weeks (F/MF genotypes) or 36 weeks (F/F genotype) of additional treatment. These results validate the durability of ELX/TEZ/IVA efficacy responses, with no emerging safety concerns. Among participants who had received placebo or TEZ/IVA in the respective parent studies, initiation of ELX/TEZ/IVA rapidly led to marked improvements in these efficacy measures that were consistent with the results seen in the ELX/TEZ/IVA arms of those parent studies. Thus, the results of this combined-group interim analysis demonstrate the safety and sustained efficacy of long-term ELX/TEZ/IVA treatment in pwCF 12 years old or older with one or more F508del alleles.
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The rate of pulmonary exacerbations for participants in both genotype groups was lower than in the previous 24-week interim analysis of this extension study (0.19 versus 0.30).
“During the first 144 weeks of this extension study, the estimated pulmonary exacerbation rate for patients with F/MF genotypes (0.20) was lower than in the ELX/TEZ/IVA arm of the 24-week parent study (0.37) [18] and the rate of pulmonary exacerbations for participants in both genotype groups was lower than in the previous 24-week interim analysis of this extension study (0.19 versus 0.30) [23].”
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Cites
Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele
Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., Ramsey, B. W., Taylor-Cousar, J. L., Tullis, E., Vermeulen, F., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1908639 · Cited by 2,198 · see citing works
Self-citationHeijerman, H. G. M., McKone, E. F., Downey, D. G., Van Braeckel, E., Rowe, S. M., Tullis, E., Mall, M. A., Welter, J. J., Ramsey, B. W., McKee, C. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32597-8 · Cited by 1,414 · see citing works
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Research works printed but not linked: 7
- [1]Riordan JR Rommens JM Kerem B Alon N Rozmahel R Grzelczak Z et al Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA Science 1989 245 1066 1073 2475911
- [2]Mall MA Mayer-Hamblett N Rowe SM Cystic fibrosis: emergence of highly effective targeted therapeutics and potential clinical implications Am J Respir Crit Care Med 2020 201 1193 1208 31860331 PMC7233349
- [3]Bell SC Mall MA Gutierrez H Macek M Madge S Davies JC et al The future of cystic fibrosis care: a global perspective Lancet Respir Med 2020 8 65 124 31570318 PMC8862661
- [7]Keating D Marigowda G Burr L Daines C Mall MA McKone EF et al VX16-445-001 Study Group VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles N Engl J Med 2018 379 1612 1620 30334692 PMC6289290
- [8]Griese M Costa S Linnemann RW Mall MA McKone EF Polineni D et al A phase 3, open-label extension study of elexacaftor/tezacaftor/ivacaftor: interim analysis of safety and efficacy in people with cystic fibrosis and F508del/minimal function (F/MF) or F508del/F508del (F/F) genotypes. Presentation at the 43rd Annual European Cystic Fibrosis Conference Virtual; September 24–25, 2020
- [9]Taylor-Cousar JL Mall MA Ramsey BW McKone EF Tullis E Marigowda G et al Clinical development of triple-combination CFTR modulators for cystic fibrosis patients with one or two F508del alleles ERJ Open Res 2019 5 00082-2019 31218221 PMC6571452
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Bower, J. K., Volkova, N., Ahluwalia, N., Sahota, G., Xuan, F., Chin, A., Weinstock, T. G., Ostrenga, J., & Elbert, A. (2023) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2023.03.002 · Cited by 140 · see citing works
Daines, C. L., Tullis, E., Costa, S., Linnemann, R. W., Mall, M. A., McKone, E. F., Polineni, D., Quon, B. S., Ringshausen, F. C., Rowe, S. M., et al. (2023) · European Respiratory Journal · doi:10.1183/13993003.02029-2022 · Cited by 100 · see citing works
Self-citation
- Authors
- Griese, M., Costa, S., Linnemann, R. W., Mall, M. A., McKone, E. F., Polineni, D., Quon, B. S., Ringshausen, F. C., Taylor-Cousar, J. L., Withers, N. J., Moskowitz, S. M., & Daines, C. L.
- Affiliations
- German Center for Lung Research (DE)
- University of Messina (IT)
- Emory University (US)
- St. Vincent's University Hospital (IE)
- University of Kansas (US)
- University of British Columbia (CA)
- Medizinische Hochschule Hannover (DE)
- National Jewish Health, Denver, Colorado
- Royal Devon & Exeter NHS Foundation Trust (GB)
- Vertex Pharmaceuticals (United States) (US)
- University of Arizona (US)
- Corresponding author
- Griese, Matthias
- ORCID
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-02-01
- Volume
- 203
- Issue
- 3
- Pages
- 381-385
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC8020728
- OpenAlex
- W3089095538
- Cited by
- 163
- References
- 2
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 28 · 2023: 43 · 2022: 29 · 2021: 28 · 2020: 4
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of General Medical Sciences (P20GM130423)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- elexacaftor/tezacaftor/ivacaftor, cystic fibrosis, F508del mutation, long-term treatment safety, sustained efficacy, CFTR modulator therapy, open-label extension, ppFEV1, sweat chloride, body mass index, patient-reported outcomes, pulmonary exacerbations, adverse events
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Aminophenols, Child, Cystic Fibrosis, Drug Combinations, Drug Therapy, Combination, Humans, Indoles, Middle Aged, Pyrazoles, Pyridines, Quinolines, Treatment Outcome, Cystic Fibrosis Transmembrane Conductance Regulator, Benzodioxoles, Young Adult
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