Trikafta for cystic fibrosis

Cystic fibrosis is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein, and nearly 90 percent of patients carry at least one copy of the commonest mutation, Phe508del, also written F508del. Elexacaftor is a newer type of CFTR corrector. In a phase 2 trial in patients with one Phe508del copy and a second, minimal-function mutation, elexacaftor given with the older drugs tezacaftor and ivacaftor improved the function of the faulty protein and the patients' clinical course.

Peter Middleton, Marcus Mall and colleagues then ran a phase 3, double-blind trial in 403 patients aged 12 or older with that genotype, assigned at random to the three drugs or placebo for 24 weeks, with lung function at week 4 as the primary end point. Compared with placebo, percent-predicted FEV1 was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks. Pulmonary exacerbations were 63 percent less frequent, sweat chloride fell by 41.8 millimoles per liter (to 57.9 at week 24, against 102.4 with placebo), and the respiratory score of a quality-of-life questionnaire rose by 20.2 points.

FDA approved the combination, sold by Vertex Pharmaceuticals as Trikafta tablets, on 21 October 2019 for patients 12 and older with at least one F508del mutation. The trial report appeared in the New England Journal of Medicine ten days later, on 31 October. Because nearly 90 percent of people with cystic fibrosis have at least one F508del copy, a single oral treatment aimed at the faulty protein itself was now available to most patients old enough to take it.