The U.S. Food and Drug Administration (FDA) has approved ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), a novel once-daily triple combination therapy developed by Vertex Pharmaceuticals, for the treatment of cystic fibrosis (CF) in patients aged 6 years and older. This approval marks a significant advancement in CF treatment, offering a new option for patients with at least one F508del mutation or another mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to ALYFTREK.
Clinical Efficacy and Safety
The FDA's decision was supported by data from a comprehensive Phase 3 clinical program involving over 1,000 patients across more than 20 countries. Key findings from these trials include:
- Non-inferiority to TRIKAFTA: Studies in patients aged 12 years and older demonstrated ALYFTREK's non-inferiority to TRIKAFTA (elexacaftor/tezacaftor/ivacaftor) in terms of absolute change from baseline in percent predicted FEV1 (ppFEV1), a measure of lung function.
- Improved Sweat Chloride Levels: ALYFTREK showed statistically significant improvements in sweat chloride (SwCl) levels compared to TRIKAFTA, indicating enhanced CFTR protein function.
- Safety Profile: In a Phase 3 study involving children aged 6-11 years, ALYFTREK demonstrated a favorable safety profile, with secondary endpoints supporting its benefit in this age group.
Claire L. Keating, M.D., Co-Director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University, highlighted that ALYFTREK demonstrated non-inferiority to TRIKAFTA in ppFEV1 response and statistically significant improvement in SwCl across a broad range of genotypes, marking a welcomed advancement for the treatment of CF. She added that ALYFTREK has the potential to improve the care of patients with CF.
Convenience and Expanded Eligibility
ALYFTREK is the first once-daily CFTR modulator, addressing a significant unmet need for more convenient dosing. A recent survey indicated that approximately 75% of physicians view more convenient dosing as a very high unmet need for CF patients. The once-daily regimen is particularly beneficial given the requirement to take CFTR modulators with fat-containing food.
Moreover, ALYFTREK expands treatment eligibility to approximately 150 people with CF in the U.S. who have one of 31 mutations not responsive to other CFTR modulator therapies.
Boxed Warning and Monitoring
The drug's label includes a boxed warning for potential drug-induced liver injury and liver failure, similar to other CFTR modulators. Regular liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) are recommended before initiating ALYFTREK, every month during the first 6 months of treatment, every 3 months for the next 12 months, and at least annually thereafter. The drug is contraindicated in patients with severe hepatic impairment.
Cystic Fibrosis Background
Cystic fibrosis is a rare, life-shortening genetic disease affecting more than 92,000 people globally. It is caused by mutations in the CFTR gene, leading to a defective or missing CFTR protein. This results in the buildup of abnormally thick, sticky mucus in the lungs, liver, pancreas, and other organs, leading to chronic lung infections, progressive lung damage, and other complications.
Ongoing Regulatory Review
ALYFTREK is also under regulatory review by global health authorities in the European Union, the United Kingdom, Canada, Switzerland, Australia, and New Zealand.
