ALYFTREK phase 3 data support pediatric CFTR modulator submissions

Vertex Pharmaceuticals reported new phase 3 data for vanzacaftor/tezacaftor/deutivacaftor (ALYFTREK) in children aged 2 to 5 years with cystic fibrosis (CF) and responsive CFTR genotypes, including F508del/F508del and F508del/minimal function genotypes, at the European Cystic Fibrosis Conference. The company said it plans to begin global regulatory submissions for this pediatric age group in the first half of 2026.¹

“The data we’re presenting today bring us to the cusp of our 25-year mission to advance medicines that restore CFTR function to people living with CF,” Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex, said in the company announcement.¹

The data extend the pediatric development program for ALYFTREK, a once-daily triple CFTR modulator regimen currently indicated in the United States for patients aged 6 years or older with CF and at least 1 responsive CFTR variant or a variant resulting in CFTR protein production.² The use of ALYFTREK in children aged 2 to 5 years remains investigational.¹

In the 24-week, phase 3, open-label study, 67 children aged 2 to 5 years completed treatment with ALYFTREK. The primary end point was safety and tolerability. According to Vertex, treatment was generally safe and well tolerated, with findings consistent with the established safety profile of the regimen.¹

The main efficacy signal reported was change in sweat chloride concentration, a biomarker of CFTR function. Children entered the study from a baseline on elexacaftor/tezacaftor/ivacaftor (TRIKAFTA), and ALYFTREK treatment was associated with a mean sweat chloride reduction of −9.6 mmol/L through week 24 (95% CI, −12.1 to −7.0). Vertex reported that 92% of participants achieved sweat chloride concentrations less than 60 mmol/L, the commonly used diagnostic threshold for CF, and 65% reached less than 30 mmol/L.¹

Because participants were already receiving TRIKAFTA at baseline, the magnitude of sweat chloride change should be interpreted as incremental improvement over an existing highly effective modulator regimen rather than as treatment-naive efficacy. The open-label design, small sample size, and biomarker-centered outcome also limit conclusions about longer-term effects on pulmonary exacerbations, growth, nutrition, pancreatic function, or structural lung disease.

Vertex also presented 96-week interim analyses from 2 open-label extension studies evaluating ALYFTREK in patients aged 6 to 11 years and in those aged 12 years or older. The company stated that the interim analyses supported longer-term safety and efficacy, although detailed numerical findings were not included in the announcement.¹

In a separate pediatric update, Vertex presented results from a 24-week, phase 3, open-label study of TRIKAFTA in 54 children aged 12 to younger than 24 months. The primary end point was safety and tolerability. TRIKAFTA was reported to be generally safe and well tolerated, with safety findings consistent with its known profile. Treatment was associated with a mean sweat chloride reduction of −71.8 mmol/L from a baseline without CFTR modulator therapy through week 24; 98.0% of children achieved sweat chloride concentrations less than 60 mmol/L, and 68.6% reached less than 30 mmol/L.¹ Vertex said it has initiated global regulatory submissions for TRIKAFTA in this age group. TRIKAFTA is currently indicated in the United States for patients aged 2 years or older with eligible CFTR variants.³

CF is an autosomal recessive, multisystem disease caused by pathogenic variants in CFTR, leading to impaired chloride and bicarbonate transport and disease manifestations in the lungs, pancreas, gastrointestinal tract, hepatobiliary system, sweat glands, and reproductive tract. Earlier initiation of CFTR modulator therapy has become a major focus in pediatric CF care because organ injury begins early in life, often before overt clinical decline. The Cystic Fibrosis Foundation Patient Registry has documented improving survival in the modulator era, but substantial morbidity persists, particularly among patients with advanced disease or genotypes not responsive to currently available modulators.⁴

TRIKAFTA established the current benchmark for highly effective CFTR modulation. In a pivotal phase 3 trial involving patients aged 12 years or older with 1 F508del allele and 1 minimal function allele, elexacaftor/tezacaftor/ivacaftor improved percent predicted forced expiratory volume in 1 second and reduced sweat chloride compared with placebo.³ ALYFTREK uses vanzacaftor, tezacaftor, and deutivacaftor, combining 2 correctors with a potentiator intended to improve CFTR protein processing and channel function.²

Safety monitoring remains central for both regimens. US prescribing information for ALYFTREK and TRIKAFTA includes a boxed warning for drug-induced liver injury and liver failure, with recommendations for liver function testing before treatment, monthly testing during the first 6 months, every 3 months for the next 12 months, and at least annually thereafter.²,³ Other labeled risks include hypersensitivity reactions, cataracts in pediatric patients, drug interactions involving CYP3A modulators, and neuropsychiatric events.²,³

For clinicians, the new pediatric data suggest continued movement of CFTR modulation into younger age groups, but regulatory review and peer-reviewed publication of the full data will be important before practice implications can be fully assessed.

References

1. Vertex Pharmaceuticals Incorporated. Vertex presents new data on ALYFTREK at European Cystic Fibrosis Conference. BusinessWire. June 5, 2026. Accessed June 8, 2026. https://www.businesswire.com/news/home/20260605191367/en/Vertex-Presents-New-Data-on-ALYFTREK-at-European-Cystic-Fibrosis-Conference

2. ALYFTREK (vanzacaftor, tezacaftor, and deutivacaftor) prescribing information. Vertex Pharmaceuticals Incorporated. Accessed June 8, 2026. https://pi.vrtx.com/files/uspi_vanzacaftor_tezacaftor_deutivacaftor.pdf

3. TRIKAFTA (elexacaftor, tezacaftor, and ivacaftor) prescribing information. Vertex Pharmaceuticals Incorporated. Accessed June 8, 2026. https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf

4. Cystic Fibrosis Foundation. Patient Registry 2023 Annual Data Report. Cystic Fibrosis Foundation; 2024.