Alyftrek, triple-combination CF treatment, approved in UK
Vertex says it's working to ensure availability through NHS
The U.K. Medicines and Healthcare Products Regulatory Agency approved Alyftrek (vanzacaftor, tezacaftor, and deutivacaftor) as a cystic fibrosis (CF) treatment for patients ages 6 and older.
The triple-combination CFTR modulator, developed by Vertex Pharmaceuticals, is indicated for patients who have at least one copy of a responsive mutation, including the most common F508del, the most frequent CF-causing mutation.
Vertex said it’s working with the National Institute for Health and Care Excellence (NICE) to ensure the treatment is available to eligible patients through the National Health Service. “The approval of Alyftrek, our fifth CFTR modulator regimen, represents another significant milestone in that journey for people with CF in the UK,” Carmen Bozic, MD, Vertex’s chief medical officer, said in a company press release.
CF results from mutations in the CFTR gene that lead to the dysfunction or absence of a protein, also known as CFTR, which is essential for the flow of salt and water across the cell membrane. CFTR mutations lead to an unusually thick and sticky mucus builds up in several organs, driving most disease symptoms. Having no or abnormal CFTR protein also leads to high levels of chloride, a salt molecule, in sweat.
Next-generation CF treatment
CFTR modulators work by improving the functionality of the CFTR in certain people with CF.
Alyftrek was developed as a next-generation successor to Trikafta (elexacaftor/tezacaftor/ivacaftor), another approved CFTR modulator. The new treatment includes tezacaftor in combination with two new modulators, vanzacaftor (VX-121) and deutivacaftor (VX-561). It was designed to have a higher efficacy at a more convenient, once- daily dosing schedule than Trikafta, which is taken twice daily.
Vanzacaftor and tezacaftor aim to help the CFTR fold correctly and reach the cell surface. Deutivacaftor is a potentiator, meaning it increases the function of CFTR at the cell surface by making it more likely that the channel protein is open.
Alyftrek’s approval was based on data from three Phase 3 clinical trials: SKYLINE 103 (NCT05076149) and SKYLINE 102 (NCT05033080), which enrolled CF patients 12 and older, and an ongoing study (NCT05422222) in children ages 1 to 11. This trial is recruiting patients at several U.S. sites.
Results generally showed that Alyftrek was superior to Trikafta at reducing sweat chloride levels, indicating it has a more potent effect on CFTR functionality. Both treatments had comparable effects at stabilizing lung function, and showed similar safety.
“[Alyftrek] 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,” said Alex Horsley, PhD, professor of respiratory medicine at the University of Manchester. “Children and adults taking the new triple combination therapy were more likely to have carrier levels of sweat chloride compared to those on [Trikafta], which we hope will translate to reduced risk of developing CF-related complications in the long term.”
Carriers are people without CF symptoms who carry one copy of a CFTR gene mutation but do not have any manifestation of disease.
Alyftrek recently received U.S. Food and Drug Administration (FDA) approval, and is under regulatory review in the European Union, Switzerland, Canada, Australia, and New Zealand.
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