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

Vertex Announces Marketing Authorization in Canada for ALYFTREK, a Once-Daily Next-Generation CFTR Modulator for the Treatment of Cystic Fibrosis (Canada Newswire) - "Vertex Pharmaceuticals...announced that Health Canada has granted Marketing Authorization for ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), a new triple combination therapy for patients 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....This approval is based on a comprehensive Phase 3 pivotal program, 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)."

Canada approval • Cystic Fibrosis

Insurance approval rates and barrier to access for vanzacaftor-tezacaftor-deutivacaftor at a single pediatric CF center (NACFC 2025) - No abstract available

Clinical • Reimbursement • US reimbursement • Pediatrics

Alyftrek in Adults (NACFC 2025) - No abstract available

Clinical

Alyftrek in Peds (NACFC 2025) - No abstract available

Vertex Reports Second Quarter 2025 Financial Results (Businesswire) - "Vertex delivered a strong quarter of revenue growth with each of our three product launches - ALYFTREK, JOURNAVX, and CASGEVY - contributing....Total revenue increased 12% to $2.96 billion compared to the second quarter of 2024, primarily driven by the continued performance of cystic fibrosis (CF) therapies and early contributions from the three ongoing launches. In the U.S., total revenue increased 14% to $1.85 billion due to continued strong patient demand and favorable gross-to-net versus prior year. Outside the U.S., total revenue increased 8% to $1.12 billion due to strong performance across multiple geographies."

Sales • Beta-Thalassemia • Cystic Fibrosis • Pain • Sickle Cell Disease

Vertex Announces Broad Reimbursement Agreement With NHS England for ALYFTREK (Deutivacaftor/Tezacaftor/Vanzacaftor) an Innovative Once-Daily CFTR Modulator for the Treatment of Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals Incorporated...announced today that it has reached a broad reimbursement agreement with NHS England for Vertex’s cystic fibrosis (CF) medicine ALYFTREK (deutivacaftor/tezacaftor/vanzacaftor). This agreement comes as the National Institute for Health and Care Excellence (NICE) has issued a positive final draft recommendation for this medicine. This next-in-class triple combination treatment is licensed for people living with CF aged 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene....Following the European regulatory approval, eligible patients in Ireland, Denmark and Germany will be the first ones to access deutivacaftor/tezacaftor/vanzacaftor in the European Union. Vertex will continue to work with reimbursement bodies across the European Union member states to ensure access for all eligible patients as quickly as possible."

Reimbursement • Cystic Fibrosis

Divergent Neurobehavioral Effects of CFTR Modulators Elexacaftor and Ivacaftor in Mice. (PubMed, bioRxiv) - "Among these, the elexacaftor-tezacaftor-ivacaftor combination (Trikafta) and its updated formulation, vanzacaftor-tezacaftor-deutivacaftor (Alyftrek), represent major therapeutic milestones. Additionally, we confirmed the presence of Cftr mRNA in the amygdala and hippocampus, brain regions implicated in anxiety and depression. These findings provide preclinical support for the reported mental health side effects experienced by some people with CF and offer new insights into CFTR function within the central nervous system, potentially guiding the development of future CF therapies with improved neuropsychiatric profiles."

Journal • Preclinical • CNS Disorders • Cystic Fibrosis • Depression • Genetic Disorders • Immunology • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases • CFTR

Vertex Announces European Commission Approval of ALYFTREK, a New Once-Daily CFTR Modulator for the Treatment of Cystic Fibrosis (Businesswire) - "Vertex Pharmaceuticals...announced that the European Commission has granted approval 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....In two head-to-head pivotal clinical trials, deutivacaftor/tezacaftor/vanzacaftor was non-inferior to KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor on ppFEV1 and superior at reducing sweat chloride, demonstrating greater improvement in CFTR function."

EMA approval • Cystic Fibrosis

​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