Vertex Pharmaceuticals Incorporated announced that data on TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor, were presented at this year's European Cystic Fibrosis Society's (ECFS) 47th European Cystic Fibrosis Conference held June 5-8, 2024, in Glasgow, Scotland. Data from a randomized, double-blind, Phase 3 study (abstract WS06.04) demonstrated that people with CF who have rare, non-F508del mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsive to TRIKAFTAin vitro demonstrated clinical benefit from receiving TRIKAFTA. Compared to placebo, lung function improved by 9.2 percentage points as measured by ppFEV1, CFTR function improved (as measured by mean sweat chloride concentration reductions of 28.3 mmol/L), and pulmonary exacerbations were reduced by 72% per year.

Safety and tolerability were generally consistent with the established safety profile of TRIKAFTA. Vertex also presented the interim analysis (IA) of a registry-based study of real-world data collected from people with CF initiating TRIKAFTA from 2019-20 in the U.S. and KAFTRIO plus ivacaftor from 2020-21 in Germany (abstract WS01.04). The ongoing five-year post-authorization study is the largest real-world study of people with CF treated with TRIKAFTA/KAFTRIO to date, including more than 16,000 people with CF from the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) and approximately 3,000 people with CF from the German CF Registry.

The IA showed clinically meaningful, disease-modifying benefits for TRIKAFTA/KAFTRIO, including a 76% and 70% reduction in the cumulative annual rate of pulmonary exacerbations in the U.S. and in Germany, respectively, compared to the year prior to TRIKAFTA/KATRIO treatment. In addition, there was a 62% lower rate of death in the U.S. and 84% lower in Germany; and an 86% lower rate of lung transplant in the U.S. and 96% lower in Germany compared to the 2019 U.S. CFFPR and German CF Registry populations (pre-TRIKAFTA/KAFTRIO). No new safety concerns were identified.

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. In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly.

TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane.

The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways. TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or another mutation that is responsive to treatment with TRIKAFTA. Patients should talk to their doctor to learn if they have an indicated CF gene mutation.

It is not known if TRIKAFTA is safe and effective in children under 2 years of age.