Vertex Pharmaceuticals Incorporated announced that the U.S. Food and Drug Administration has accepted its New Drug Application for investigational once-daily vanzacaftor/tezacaftor/deutivacaftor triple combination therapy (vanza triple) 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 responsive to the vanza triple. Vertex used a priority review voucher for this submission reducing the review time from 10 months to 6 months, resulting in a Prescription Drug User Fee Act (PDUFA) target action date of January 2, 2025. Vertex also received validation of its Marketing Authorization Application (MAA) submission by the European Medicines Agency (EMA) in the EU for patients ages 6 years and older.

The company has also submitted in Canada, Australia, Switzerland and the U.K. Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene.

Children must inherit two defective CFTR genes ? one from each parent ? to have CF, and these mutations can be identified by a genetic test.

While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs.

In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving. Vertex CF medicines are treating over 65,000 people with CF across 60 countries on six continents.

This represents 2/3 of the diagnosed people with CF eligible for CFTR modulator therapy. 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 =60 mmol/L, while levels between 30-59 indicate CF is possible and more testing may be needed to make the diagnosis of CF.

A SwCl level of <30 mmol/L is seen in people who carry one copy of a CFTR gene mutation but do not have any manifestation of disease (carriers). Higher levels of SwCl are associated with more severe disease. Restoring CFTR function leads to lower levels of SwCl.

SwCl levels below 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. Restoring SwCl levels below 30 mmol/L has long been the ultimate treatment goal for Vertex, as levels below 30 mmol/L are considered normal and are typical of CF carriers who do not have disease.