Pathogenetic treatment of cystic fibrosis: expanding access to drugs

Background. Cystic fibrosis is a hereditary monogenic disease inherited in an autosomal recessive pattern, caused by a mutation in the cystic fibrosis transmembrane regulator (CFTR) gene and characterized by multisystem involvement of exocrine glands, with particularly severe respiratory disorders. Until recently, the treatment of cystic fibrosis was mainly symptomatic. A revolutionary breakthrough in the treatment of the disease is associated with the emergence of pathogenetic therapy with CFTR modulators, which eliminate the disturbances in the functioning of the CFTR chloride channel that underlie the disease. The article provides a detailed review of the classification of CFTR mutations and the corresponding classes of modulator drugs: potentiators (ivakaftor, detivakaftor), correctors (elexacaftor, tezacaftor, lumacaftor, vanzacaftor). Particular attention is paid to the highly effective triple combination of elexacaftor/tezacaftor/ivacaftor, which has become the gold standard for the treatment of cystic fibrosis. It is emphasized that early initiation of modulator therapy can prevent the development of severe manifestations of the disease. The epidemiological indicators of cystic fibrosis in Russia are considered separately, where there is a lag in the proportion of adult patients and the availability of targeted therapy compared to Western Europe and North America. As a solution to the problem of the availability of expensive drugs, data on generic triple therapy drugs are presented. The results of Russian studies demonstrating the bioequivalence, comparable efficacy, and safety of generic targeted drugs for the treatment of cystic fibrosis compared to the original drugs are presented. Conclusion. CFTR modulators offer a personalized approach to the treatment of cystic fibrosis. The widespread use of both original and generic CFTR modulator drugs is a key factor in improving the effectiveness and accessibility of pathogenetic therapy, which will improve the survival and quality of life of patients with cystic fibrosis.