Study of the efficacy and safety of the generic drug ivacaftor + tezacaftor + elexacaftor/ivacaftor (trade name Trilexa®)

Cystic fibrosis (CF) is a universal exocrine disorder that affects virtually all organs and systems containing exocrine glands. A genetic defect in the cystic fibrosis transmembrane conductance regulator gene leads to increased viscosity of exocrine gland secretions, primarily in the respiratory tract. CFTR modulators improve the synthesis, processing, and/or function of the defective CFTR protein, which is a chloride channel. Objective. To evaluate the efficacy of the generic drug ivacaftor + tezacaftor + elexacaftor/ivacaftor (trade name Trilexa®), in a group of patients not previously receiving triple targeted therapy after 3 months of treatment in patients who have not previously received the first threecomponent CFTR modulator. Methods. Data from the Russian CF Patient Registry, entered into the “Targeted Therapy” block, were analyzed for the period from January to August 2025 (main group) and for the period from January 2022 to August 2022 (comparison group). Two groups of patients were identified: Group 1 included 28 pediatric patients (12 boys/16 girls) with a confirmed diagnosis of cystic fibrosis, who started receiving triple targeted therapy generic drug ivacaftor + tezacaftor + elexacaftor/ivacaftor. Group 2, the comparison group, consisted of 34 pediatric patients (14 boys/20 girls) who started receiving the original triple targeted drug ivacaftor + tezacaftor + elexacaftor/ivacaftor (trade name Trikafta®). Results. When assessing the nutritional status, a significant increase in BMI was shown in both groups of patients at the start and after 3 months; p < 0.001. Sweat test parameters (conductivity in mmol/L) differed significantly both at the start of therapy and after a month in both groups. The difference between the average sweat test values (Δ mmol/L) in both groups were comparable and did not differ from each other. The groups did not differ in the number of adverse events, which were mild and did not lead to drug discontinuation. Both drugs, the original and the generic, demonstrated safety and good tolerability. Group 1 value was 43 (35.5; 55), and Group 2 value was 42 (32; 50.3); p = 0.86. FEV1 and FVC indicators showed a tendency to increase with both drugs, but it was not significant in both groups. Conclusion. The triple targeted therapy with the use of generic drug ivacaftor + tezacaftor + elexacaftor/ivacaftor is effective and safe in this sample of pediatric patients with cystic fibrosis. No significant differences were found between generic drug and the original drug in relation to the main efficacy criteria during 3 months of use. The frequency, spectrum, and severity of reported adverse events associated with the use of generic drug were comparable to those associated with the use of the original drug.