Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) has announced that the U.S. Food and Drug Administration (FDA) has approved ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), a once-daily, next-generation CFTR (cystic fibrosis transmembrane conductance regulator) modulator. ALYFTREK is approved for the treatment of cystic fibrosis (CF) in individuals aged 6 years and older who have at least one F508del mutation or other mutations in the CFTR gene responsive to ALYFTREK. This approval represents a significant advancement in CF therapy.
“We are proud to introduce ALYFTREK, our fifth FDA-approved CFTR modulator,” said Reshma Kewalramani, M.D., CEO and President of Vertex. “For more than two decades, our goal has been to address the root cause of CF and improve the lives of people living with this challenging disease. ALYFTREK, with its once-daily dosing, improved efficacy for 31 additional mutations, and better sweat chloride outcomes compared to TRIKAFTA, takes us one step closer to this goal.”
Comprehensive Phase 3 Data Supports Approval
The approval of ALYFTREK is based on one of the most extensive Phase 3 pivotal trials in CF, which involved over 1,000 patients across more than 200 sites in over 20 countries. The trial demonstrated that ALYFTREK was non-inferior to TRIKAFTA, Vertex’s previously approved CF treatment, in improving the absolute change in lung function (ppFEV1). Additionally, ALYFTREK showed a statistically significant improvement in sweat chloride levels, a key biomarker for CF, compared to TRIKAFTA.
In the Phase 3 trial of children aged 6-11 years, ALYFTREK showed positive results for safety and efficacy, with improvements in lung function and sweat chloride levels, supporting its use in pediatric patients. ALYFTREK was generally well tolerated across all age groups.
A First for Once-Daily Dosing
ALYFTREK is the first CFTR modulator to be approved as a once-daily treatment, addressing a significant need for convenience among CF patients. A recent survey revealed that around 75% of physicians cited improved dosing convenience as a major unmet need for CF patients. Since CFTR modulators must be taken with fat-containing foods, ALYFTREK’s once-daily regimen could help streamline treatment for patients, offering a simpler dosing schedule.
Additionally, ALYFTREK provides a potentially life-changing option for approximately 150 U.S. CF patients with one of 31 mutations that are now eligible for treatment with a CFTR modulator for the first time.
Global Regulatory Review Underway
ALYFTREK is under regulatory review in multiple countries, including the European Union, the United Kingdom, Canada, Australia, Switzerland, and New Zealand. Vertex expects further approvals in these regions in the near future.
About Cystic Fibrosis
Cystic fibrosis is a progressive, life-threatening genetic disorder that affects approximately 92,000 people worldwide. It is caused by mutations in the CFTR gene, leading to defective or absent CFTR proteins, which results in thick, sticky mucus that damages organs such as the lungs, pancreas, and liver. The disease causes chronic respiratory infections and progressive lung damage, with many patients dying in their 30s. However, with advancements in CFTR modulators like ALYFTREK, survival rates are steadily improving.
ALYFTREK’s U.S. Indication and Important Safety Information
ALYFTREK is approved for patients aged 6 years and older with at least one F508del mutation or another CFTR gene mutation responsive to the drug. If a patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm eligibility.
Boxed Warning: ALYFTREK carries a boxed warning for liver injury and liver failure, observed in patients taking similar medications. Liver function tests must be monitored regularly, especially during the first 6 months of treatment. Patients should be closely monitored for signs of liver injury and treated accordingly.
Other safety concerns include hypersensitivity reactions (including anaphylaxis) and potential reduced effectiveness when used with CYP3A inducers. ALYFTREK should not be used in patients with severe hepatic impairment.
Conclusion
With its once-daily dosing and improved efficacy for a broader range of CF mutations, ALYFTREK represents a promising treatment option for people living with cystic fibrosis. Vertex’s commitment to advancing CF care continues with this approval, marking another milestone in its mission to improve patient outcomes and quality of life for individuals with this devastating disease.
