Focus area: Physicians
A New combination therapy against an OLD disease: Tezacaftor-Ivacaftor in CF homozygous for Phe508del patients
Efficacy and safety of combination therapy with Tezacaftor-Ivacaftor could support its use in a group of CF patients.
CFTR modulators are a family of new compounds that target specific ionic channel defects caused by mutations in CFTR gene, treating the underlying pathogenic mechanisms cause of Cystic Fibrosis (CF).
Ivacaftor, the first approved CFTR modulator, increases the probability of channel opening of normal and mutant CFTR protein. Ivacaftor, as a single drug or in combination with other modulators such as Lumacaftor, have been associated with a rate of progressive decline in lung function that is lower than the rate observed among untreated patients.
Tezacaftor is an investigational CFTR corrector that, in combination with Ivacaftor, has shown efficacy in preclinical studies and has shown enhanced CFTR function and improved lung function in a phase 2 clinical trial involving patients homozygous for Phe508del mutation or heterozygous for the Phe508del and G551D mutations.
A very recent and interesting paper, published on November 2017 at New England Journal of Medicine, reported the findings of a phase 3, randomized, double-blind, multicenter, placebo-controlled, clinical trial that evaluated the efficacy and safety of Ivacaftor-Tezacaftor combination in CF patients, 12 years of age or older, who were homozygous for the Phe508del mutation. The study was conducted for a 24 week’s period at 91 sites of United States, Canada and Europe from January 2015 to January 2017. Tezacaftor-Ivacaftor resulted in a significantly lower rate of pulmonary exacerbations and in a greater improvement in quality of life and lung function than placebo. The use of Tezacaftor-Ivacaftor was not associated with a significant effect on BMI (Body Mass Index), that was seen in previous Ivacaftor studies. The incidence of adverse events was similar in the Tezacaftor-Ivacaftor group and the placebo group.
The improved efficacy and safety of combination therapy with Tezacaftor-Ivacaftor, as compared with currently available therapy, could support its use in a broad range of CF patients.
Taylor-Cousar JL, Munck A, McKone EF et al. Tezacaftor-Ivacaftor in patients with Cystic Fibrosis homozygous for Phe508del. NEJM, 2017;377:2013-2023