A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One <i>F508del</i> Allele

Zemanick, Edith T.; Taylor‐Cousar, Jennifer L.; Davies, Jane C.; Gibson, Ronald L.; Mall, Marcus; McKone, Edward F.; McNally, Paul; Ramsey, Bonnie W.; Rayment, Jonathan H.; Rowe, Steven M.; Tullis, Elizabeth; Ahluwalia, Neil; Chu, Chenghao; Ho, Thang; Moskowitz, Samuel M.; Noël, Sabrina; Tian, Simon; Waltz, David A.; Weinstock, Tanya G.; Xuan, Fengjuan; Wainwright, Claire; McColley, Susanna A.

doi:10.1164/rccm.202102-0509oc

Cited by 180 publications

(174 citation statements)

References 35 publications

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“…The development and recent approval of an increasing number of CFTR modulator drugs has created an unprecedented opportunity to treat the basic defect in a growing number of patients with CF [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. However, clinical trials of CFTR modulators showed heterogeneous responses in clinical outcomes as well as sweat chloride concentration among patients with identical CFTR genotypes.…”

Section: Icm As Outcome Measure Of In Vivo Response To Cftr-directed Therapeuticsmentioning

confidence: 99%

“…Recently, a triple combination of the two correctors elexacaftor and tezacaftor with the potentiator ivacaftor showed substantial clinical improvement in patients with CF with at least one F508del allele [ 10 , 11 ]. As a result, effective CFTR modulators have recently been approved and are becoming available for the treatment of approximately 90 % of CFTR genotypes [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Despite this unprecedented breakthrough in precision medicine of the underlying CF defect, there are still approximately 10% of patients with CFTR genotypes that cannot be treated with current CFTR-directed therapeutics.…”

Section: Potential Use Of Icm For Personalized Medicine For Patients With Rare Mutations and High Unmet Needmentioning

confidence: 99%

“…Recent breakthroughs in cystic fibrosis (CF) transmembrane conductance regulator (CFTR)-directed therapies have heralded a new era of precision medicine for patients with CF [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Biomarkers that are sensitive to detect improvement of CFTR function in individual patients could help to assess individual treatment responses to these therapies targeting the underlying CF defect.…”

Section: Introductionmentioning

confidence: 99%

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Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis

Graeber

Vitzthum

Mall

2021

JPM

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Refinement of personalized treatment of cystic fibrosis (CF) with emerging medicines targeting the CF basic defect will likely benefit from biomarkers sensitive to detect improvement of cystic fibrosis transmembrane conductance regulator (CFTR) function in individual patients. Intestinal current measurement (ICM) is a technique that enables quantitative assessment of CFTR chloride channel function in rectal tissues or other intestinal epithelia. ICM was originally developed to study the CF ion transport defect in the intestine and has been established as a sensitive biomarker of CFTR function and diagnostic test for CF. With the emergence of CFTR-directed therapeutics, ICM has become an important tool to estimate the level of rescue of CFTR function achieved by approved CFTR modulators, both at the level of CFTR genotype groups, as well as individual patients with CF. In combination with preclinical patient-derived cell culture models, ICM may aid the development of targeted therapies for patients with rare CFTR mutations. Here, we review the principles of ICM and examine how this CFTR biomarker may be used to support diagnostic testing and enhance personalized medicine for individual patients with common as well as rare CFTR mutations in the new era of medicines targeting the underlying cause of CF.

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Section: Icm As Outcome Measure Of In Vivo Response To Cftr-directed Therapeuticsmentioning

confidence: 99%

Section: Potential Use Of Icm For Personalized Medicine For Patients With Rare Mutations and High Unmet Needmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis

Graeber

Vitzthum

Mall

2021

JPM

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“…Recently released phase 3 data for ELX/TEZ/IVA use in children 6 to 11 years of age showed positive safety and tolerability results, as well as secondary endpoint improvements in ppFEV1, sweat chloride, Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores, body mass index (BMI), as well as number of pulmonary exacerbations and hospitalizations. 1 Studies have also documented that initiating HEMT at an earlier age has the potential to alter the progression and prognosis of CF. [2][3][4] Based on this information, a supplemental New Drug Application to expand the use of ELX/TEZ/IVA to include children 6 to 11 years was submitted in early 2021 with a targeted decision date of June 2021.…”

Section: Introductionmentioning

confidence: 99%

Early insurance coverage of elexacaftor/tezacaftor/ivacaftor for cystic fibrosis in children 6 to 11 years of age

Anderson

McCoy

Pettit

et al. 2021

Preprint

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Introduction: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (HEMT) originally approved in 2019 for use in patients 12 years of age and older with at least one F508del mutation or a mutation in the CFTR gene that is responsive based on in vitro data. This report describes coverage of ELX/TEZ/IVA for CF in children 6 to 11 years of age prior to the recent age expansion by the Food and Drug Administration (FDA). Methods: An email was sent to pharmacists and pharmacy technicians through the CF Foundation LISTSERV and all responses regarding ELX/TEZ/IVA use in children 6 to 11 years of age were collected. Results: A total of 65 children from 15 CF care centers were included in the study. A total of 55 children had early coverage of ELX/TEZ/IVA for an overall approval rate of 84.6%. The median time to approval was 15 days. Lung function and weight outcomes were also positive. Conclusions: Early insurance coverage of ELX/TEZ/IVA for CF in children 6 to 11 years was achieved regardless of insurance type and should be considered an option for patients in need of HEMT therapy.

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“…Here, we learn the results of the Phase III clinical trial to prove safety and tolerability of ELX/TEZ/IVA in children aged 6 to 11 years (3). In this study, the open label use of ELX/TEZ/IVA was studied in 66 children.…”

mentioning

confidence: 99%

The Future of Highly Effective Modulator Therapy in Cystic Fibrosis

Daines

Morgan

2021

Am J Respir Crit Care Med

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A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele

Abstract: contributed equally to this article. ** Drs. Wainwright and McColley contributed equally to this article.+Associate Editor, AJRCCM (participation complies with American Thoracic Society requirements for recusal from review and decisions for authored works).

Cited by 180 publications

References 35 publications

Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis

Potential of Intestinal Current Measurement for Personalized Treatment of Patients with Cystic Fibrosis

Early insurance coverage of elexacaftor/tezacaftor/ivacaftor for cystic fibrosis in children 6 to 11 years of age

The Future of Highly Effective Modulator Therapy in Cystic Fibrosis

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