The effectiveness of a generic CFTR-modulator in a prolonged multicenter study

Abstract

Introduction. Prior to recent years, treatment of cystic fibrosis (CF) consisted primarily of symptom management. The pathogenetic therapy with CFTR modulators has emerged as a revolutionary method, supplying the capacity to correct the underlying CFTR chloride channel dysfunction. Aim. To evaluate the efficacy of the generic ivacaftor/tezacaftor/elexacaftor and ivacaftor Trileksa® in a group of patients with pediatric cystic fibrosis, who have been previously treated with branded CFTR modulator Trikafta®, over a 9-month period. Materials and methods. The Russian Cystic Fibrosis Patient Registry (RCFPR) data were analysed. A total of 156 subjects (82 girls (52.6%) and 74 boys (47.4%) aged 6 to 17 years) with a median age at treatment initiation Me (Q1; Q3) 12 (10; 14) were included in the study. Before starting the generic drug, all children received the brand-name drug. The median duration of treatment with the original drug was 25 (19; 30) months. Results. The median sweat test value achieved during treatment with the brand-name drug remained at the cutoff level of 64 (56; 81) mmol/L after 9 months of treatment with the generic drug (p1-4 = 0.93). The median FEV1 and FVC (%pred spirometry measurements) remained stable without negative changes overtime (FEV1 p1-4 = 0.40, FVC p1-4 = 0.70). The patients had significant changes in weight and height over the 9-month course of treatment. Adverse reactions to Trilexa therapy were rare, and the incidence was comparable with that observed for the generic drug. A slight increase in total bilirubin within reference ranges from 9.6 (7.4; 15.4) at baseline to 11.9 (8.9; 17.5) after 9 months was reported (p = 0.02) while the frequency of elevated liver function tests decreased from 5.2% to 3.2%. The number of patients with mental disorders increased: no depressive coditions were observed at treatment initiation, but after 9 months they were reported in 3.2% of patients. The percentage of patients with sleep disturbances increased from 1.3 to 3.8%, headaches from 3.8 to 6.4%, and fatigue from 4.7 to 6.4%. Conclusions. The generic Trileksa is not inferior to the brand-name drug, helps stabilize the achieved clinical and therapeutic outcomes and leads to further improvement in the course of the disease. It is safe, and well tolerated in patients. The long-term efficacy and safety of the drug must be monitored and continuously evaluated while on the market.