Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) / Vertex - LARVOL DELTA

​Time to reimbursement for elexacaftor/tezacaftor/ivacaftor across countries in the ECFS patient registry (ECFS 2025) - "Objectives: Due to its high price, elexacaftor/tezacaftor/ivacaftor (ETI) is inaccessible to patients unless reimbursed by national health bodies. Time to ETI reimbursement varied significantly across the ECFSPR, demonstrating a grouping of early reimbursement deals followed by prolonged negotiations in predominantly poorer countries. Lower GNI and smaller CF populations were both associated with a longer TTR. Following the recent US authorisation of vanzacaftor/tezacaftor/deutivacaftor, these findings highlight important considerations for equitable access to existing and emerging CFTR modulator therapies internationally."

Clinical • Reimbursement • US reimbursement • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Comparing elexacaftor and vanzacaftor: impact on CFTR functional rescue and protein maturation (ECFS 2025) - "Objectives: Many individuals with Cystic Fibrosis (CF) benefit from Trikafta, a combination of CFTR modulators: Elexacaftor/Tezacaftor/Ivacaftor (ETI)...It is uncertain whether the newly FDA-approved combination: Alyftrek (Vanzacaftor/Tezacaftor/Deutivacaftor; VTD) will mediate an improved clinical outcome for this segment of the population. We were prompted to compare the two Class III correctors: Elexacaftor versus Vanzacaftor... Vanzacaftor shows similar improvements to Elexacaftor in F508del-CFTR channel activity despite greater potency and efficacy in enhancing F508del-CFTR maturation, with ongoing studies exploring the mechanisms behind different molecular consequences of these modulators. Support provided by Cystic Fibrosis Canada and the Cystic Fibrosis Foundation."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor– tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials (ECFS 2025) - No abstract available

Clinical • P3 data • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

The association between sweat chloride and outcomes following treatment with CFTR modulators including vanzacaftor/tezacaftor/deutivacaftor (ECFS 2025) - No abstract available

Late-breaking abstract

Quality of life with VNZ/TEZ/D-IVA versus ELX/TEZ/IVA in people with cystic fibrosis aged ≥6 years: post hoc analyses from phase 3 randomized, controlled and open label extension trials (ECFS 2025) - "Objective: Describe the impact of vanzacaftor/tezacaftor/deutivacaftor (VNZ/TEZ/D-IVA) on quality of life using clinical trial data. The Cystic Fibrosis (CF) QuestionnaireRevised 8 dimensions (CFQ-R-8D) is a CF-specific preference-based scoring algorithm based on CFQ-R (adolescent/adult) for people with CF aged 14yrs. VNZ/TEZ/D-IVA was associated with better health-related quality of life (utility) in adolescents and adults, and with improved CF symptoms and general functioning in children aged 6-11yrs."

Clinical • HEOR • P3 data • Retrospective data • Cough • Cystic Fibrosis • Genetic Disorders • Immunology • Pain • Respiratory Diseases

Exploring the adherence to treatment with elexacaftor/tezacaftor/ivacaftor (ETI) In people with cystic fibrosis: a retrospective, dual-center observational study (ECFS 2025) - "Objectives: Elexacaftor/tezacaftor/ivacaftor (ETI) is the first triple-combination CFTR modulator approved for people with cystic fibrosis (pwCF) with responsive variants. Errors in ETI administration are common and often unrecognized by clinicians, underscoring the need for routine adherence assessments during clinic visits. In this context, the once-daily modulator vanzacaftor/tezacaftor/deutivacaftor offers potential to enhance adherence and reduce error rates."

Adherence • Observational data • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Cystic Fibrosis (Vertex Press Release) - "Vertex is enrolling and dosing studies in younger age groups — a Phase 3 study of TRIKAFTA/KAFTRIO in 1- to 2-year-olds and a Phase 3 study of ALYFTREK in 2- to 5-year-olds — to expand the labels and enable earlier treatment of children with CF; Vertex expects to advance the once-daily, next-generation 3.0 VX-828 combination into a clinical trial in people with CF this year; Vertex has implemented a temporary pause to the multiple ascending dose (MAD) portion of the Phase 1/2 study of VX-522, a nebulized CFTR mRNA therapy, in order to assess a tolerability issue."

New trial • Trial status • Cystic Fibrosis

Evaluation of Long-Term Safety and Efficacy of Vanzacaftor/Tezacaftor/Deutivacaftor in Cystic Fibrosis Participants 1 Year of Age and Older (clinicaltrials.gov) - P3 | N=174 | Enrolling by invitation | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: Oct 2030 ➔ Jul 2029 | Trial primary completion date: Oct 2030 ➔ Jul 2029

Trial completion date • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Vertex Receives CHMP Positive Opinion for ALYFTREK, a New Once-Daily CFTR Modulator for the Treatment of Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals...announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for ALYFTREK (deutivacaftor/tezacaftor/vanzacaftor) for the treatment of people with cystic fibrosis (CF) ages 6 years and older who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene."

CHMP • Cystic Fibrosis

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2025 (European Medicines Agency) - "On 25 April 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Alyftrek, intended for the treatment of cystic fibrosis in people aged 6 years and older who have at least one non‑class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene....Alyftrek tablets are indicated for the treatment of cystic fibrosis (CF) in people aged 6 years and older who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene."

CHMP • Cystic Fibrosis

CHMP summary of positive opinion for Alyftrek (European Medicines Agency) - "On 25 April 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Alyftrek, intended for the treatment of cystic fibrosis in people aged 6 years and older who have at least one non‑class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.... Two phase 3, randomised, double-blind clinical studies showed Alyftrek to be as effective as Kaftrio in patients with cystic fibrosis and non-class I mutations aged 12 years and older."

CHMP • Cystic Fibrosis

Correction. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Comparative Efficacy of CFTR Modulators: A Network Meta-analysis. (PubMed, Lung) - "VTD and ETI were more efficacious than Tez-Iva and Lum-Iva in pwCF with at least one F508del-CFTR-allele."

Clinical • Journal • Retrospective data • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Vanzacaftor, tezacaftor, and deutivacaftor (Alyftrek) for cystic fibrosis. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Vertex Announces Health Canada Acceptance of New Drug Submission for Vanzacaftor/Tezacaftor/Deutivacaftor, a Next-in-Class Triple Combination Treatment for Cystic Fibrosis (Canada Newswire) - "Vertex Pharmaceuticals Incorporated...today announced that Health Canada has accepted for review its New Drug Submission (NDS) for vanzacaftor/tezacaftor/deutivacaftor, a once-daily triple combination therapy for people living with cystic fibrosis (CF) ages 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene....Vanzacaftor is also undergoing regulatory review in multiple other jurisdictions, including by the Food and Drug Administration (FDA) in the U.S. and by the European Medicines Agency (EMA) in the E.U."

Canada filing • Cystic Fibrosis

Vertex Announces UK MHRA Approval of ALYFTREK (Deutivacaftor/Tezacaftor/Vanzacaftor), a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals...announced today that the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has granted approval for ALYFTREK (deutivacaftor/tezacaftor/vanzacaftor), a once-daily next-in-class triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment for people living with cystic fibrosis (CF) ages 6 years and older who have at least one F508del mutation or another responsive mutation in the CFTR gene....The deutivacaftor/tezacaftor/vanzacaftor Phase 3 trial results showed that it is possible to further improve CFTR protein function with this once-a-day, more flexible and less burdensome regimen...Vertex is working with the National Institute for Health and Care Excellence (NICE) and the NHS to ensure eligible patients can access this new therapy, which treats the underlying cause of CF, as soon as possible."

MHRA approval • Reimbursement • Cystic Fibrosis

Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. (PubMed, Lancet Respir Med) - P3 | "Vanzacaftor-tezacaftor-deutivacaftor is non-inferior to elexacaftor-tezacaftor-ivacaftor in terms of FEV1 % predicted, and is safe and well tolerated. Once daily dosing with vanzacaftor-tezacaftor-deutivacaftor reduces treatment burden, potentially improving adherence, compared with the twice daily regimen of the current standard of care. The restoration of CFTR function and the potential variants treated are also considerations that should be compared with currently available CFTR modulators."

Clinical • Journal • P3 data • Cough • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CFTR

Vanzacaftor-tezacaftor-deutivacaftor for children aged 6-11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial. (PubMed, Lancet Respir Med) - P3 | "Vanzacaftor-tezacaftor-deutivacaftor was safe and well tolerated and maintained FEV1 % predicted from elexacaftor-tezacaftor-ivacaftor baseline with further improved CFTR function. Improvements in CFTR function compared with baseline elexacaftor-tezacaftor-ivacaftor values demonstrate the potential opportunity to restore normal physiology early and prevent development or progression of cystic fibrosis. Nearly all participants had sweat chloride below the diagnostic threshold for cytstic fibrosis (<60 mmol/L) and more than half had normal levels (<30 mmol/L). Additional long-term data in children with cystic fibrosis are being collected in an open-label extension study to demonstrate clinical benefits and safety. These findings will inform health-care providers and people with cystic fibrosis regarding the benefits of early initiation of CFTR modulators."

Journal • P3 data • Constipation • Cough • Cystic Fibrosis • Fatigue • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Infectious Disease • Pain • Pulmonary Disease • Respiratory Diseases • CFTR

Vertex Announces US FDA Approval of ALYFTREK, a Once-Daily Next-in-Class CFTR Modulator for the Treatment of Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals Incorporated...announced that the U.S. Food and Drug Administration (FDA) has approved ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), a once-daily next-in-class triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator for the treatment of cystic fibrosis (CF) in people 6 years and older who have at least one F508del mutation or another mutation in the CFTR gene that is responsive to ALYFTREK...This approval is based on the most comprehensive Phase 3 pivotal program ever conducted in CF, including more than 1,000 patients across more than 20 countries and more than 200 sites...The Phase 3 studies in people with CF ages 12 years and older met their primary endpoint (non-inferiority on absolute change from baseline in ppFEV1 compared to TRIKAFTA) and all key secondary endpoints (including absolute change from baseline in sweat chloride [SwCl] compared to TRIKAFTA)."

FDA approval • Cystic Fibrosis

Vertex Reports Fourth Quarter and Full Year 2023 Financial Results (Businesswire) - "Vertex on track to submit new drug applications (NDAs) to the FDA by mid-2024 for...Vanzacaftor Triple in CF....Product revenue increased 11% to $9.87 billion compared to 2022, primarily driven by the continued strong uptake of TRIKAFTA/KAFTRIO in ex-U.S. markets...Net product revenue in 2023 increased 6% to $6.04 billion in the U.S. and increased 18% to $3.83 billion outside the U.S., compared to 2022....Vertex completed dosing in the single ascending dose (SAD) portion of the Phase 1/2 study of VX-522 in people with CF. Vertex initiated the multiple ascending dose (MAD) portion of the study; screening, enrollment and dosing are underway. Vertex expects to share data from this study in late 2024 or early 2025."

FDA filing • P1/2 data • Sales • Cystic Fibrosis

Vertex Highlights First Oral Presentation of Phase 3 Clinical Data of the Vanza Triple and New Data on Long-Term Impact of TRIKAFTA at the North American Cystic Fibrosis Conference (Businesswire) - "Vertex Pharmaceuticals Incorporated...today announced the first accepted medical presentations of the Phase 3 data on the investigational once daily vanzacaftor/tezacaftor/deutivacaftor ('vanza triple') — the potential next-in-class triple combination medicine...The vanza triple has not been approved by any global health authority....Vertex will present new data on TRIKAFTA from long-term (96 week and 192 week) studies in patients ages 2-11 years old that reinforce the sustained benefit seen in studies in older people with CF....Vertex will have four poster presentations that include clinical trial and real-world evidence data, three specifically on TRIKAFTA and one showing sustained benefits from KALYDECO, which is approved for treatment in the youngest ages."

Clinical data • P3 data • Real-world • Cystic Fibrosis

W25--Cutting-Edge Research: What's New? (NACFC 2024) - "The sessions speakers will discuss the results of the Vanzacaftor/Tezacaftor/Deutivacaftor Phase 3 trial and clinical effectiveness of Elexacaftor/Tezacaftor/Ivacaftor (ETI) on CF inflammation. • Evaluate the results of multicenter decentralized study designs and remote clinical endpoints. • Assess the novel quantitative assay for clinical measurement of elexacaftor/tezacafor/ivacaftor."

Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Respiratory Diseases

Vanzacaftor/Tezacaftor/Deutivacaftor (VNZ Triple) in Adolescents and Adults with CF: Results from Two Randomized, Active-Controlled Phase 3 Trials (NACFC 2024) - "elexacaftor/tezacaftor/ ivacaftor (ETI) is transformative in treating people with CF (PwCF) with eligible variants by improving CFTR function, but there remains an unmet need for CFTR modulators (CFTRm) capable of further restoring CFTR function toward normal. VNZ triple, a next-generation highly effective CFTRm, was noninferior to ETI in improving lung function and superior to ETI in restoring CFTR function (as measured by sweat chloride), with approximately twice the odds of restoring CFTR function to below the diagnostic threshold for CF (SwCl<60 mmol/L) and approximately triple the odds of achieving normal or carrier levels not associated with CF (SwCl<30 mmol/ L). Safety of VNZ triple was similar to that of ETI. VNZ triple sets the new standard for highly effective CFTRm."

Clinical • P3 data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Safety and efficacy of vanzacaftor/tezacaftor/deutivacaftor in children aged 6 to 11 with cystic fibrosis (NACFC 2024) - "Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the current standard of care, is transformative in treating people with CF with eligible variants by improving CFTR function, but there remains a need for a CFTR modulator capable of further restoring CFTR function toward normal (sweat chloride [SwCl]<60 mmol/L, a value below the diagnostic threshold for CF, and SwCl<30 mmol/L, a value seen in people who do not have CF/CF carriers). VNZ triple maintained normal lung function and further normalized CFTR function, measured as reduction in SwCl, beyond the improvement achieved with ELX/TEZ/IVA, bringing SwCl levels below the diagnostic threshold for CF (<60 mmol/L) in 95% of participants and to normal levels (<30 mmol/L) in 53%. VNZ triple sets the new standard for highly effective CFTR modulators, with the potential to restore normal physiology and prevent development and progression of CF manifestations."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

VX20-121-104: A Study Evaluating the Long-term Safety and Efficacy of VX-121 Combination Therapy (clinicaltrials.gov) - P3 | N=822 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: Oct 2025 ➔ Oct 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Combination therapy • Trial completion date • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases