Promising cystic fibrosis treatment receives EC approval

The European Commission has granted approval for Alyftrek (deutivacaftor/tezacaftor/vanzacaftor) for the treatment of people with cystic fibrosis (CF) aged six years and older who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Approximately 1,200 people with CF in Ireland are now eligible for this new once-daily CFTR modulator treatment. In people with CF, mutations in the CFTR gene lead to decreased quantity and/or function of the CFTR protein channel at the cell surface. Vanzacaftor and tezacaftor are designed to increase the amount of CFTR protein at the cell surface by facilitating the processing and trafficking of the CFTR protein. Deutivacaftor is a potentiator designed to increase the channel open probability of the CFTR protein delivered to the cell surface to improve the flow of salt and water across the cell membrane. 

Two head-to-head pivotal clinical trials demonstrated greater improvement in CFTR function with deutivacaftor/tezacaftor/vanzacaftor in combination with ivacaftor, over ivacaftor/tezacaftor/elexacaftor (Kaftrio).

The results of the two deutivacaftor/tezacaftor/vanzacaftor phase III clinical trials showed similar (non-inferiority) changes in ppFEV1 and superior improvement of sweat chloride (SwCl) levels compared to ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor.

In line with the reimbursement agreement in Ireland, Vertex Phamaceuticals is working with the HSE to ensure all eligible patients will have access to Alyftrek as quickly as possible.

CF is a progressive, multi-organ disease that is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Diagnosis of CF is often made by genetic testing and is confirmed by testing sweat chloride (SwCl), which measures CFTR protein dysfunction.

The diagnostic threshold for CF is SwCl ≥ 60mmol/L, while levels between 30-59 indicate CF is possible and more testing may be needed to make the diagnosis of CF. Restoring CFTR function leads to lower levels of SwCl. SwCl levels < 60 mmol/L are associated with improved outcomes such as better and more stable lung function, fewer pulmonary exacerbations, better quality of life and improved survival.