Efficacy and safety of the biosimilar medicinal product Tigerase<sup>®</sup> (dornase alfa) in long-term symptomatic treatment of patients with cystic fibrosis: results of a phase III clinical trial

The article discusses the results of a phase III clinical trial to compare the pharmacokinetics, efficacy and safety of the biosimilar medicinal product Tigerase ® (dornase alpha) (Generium JSC, Russia) and the reference medicinal product Pulmozyme ® (F.Hoffmann-La Roche Ltd, Switzerland) with the purpose of establishing their comparability for symptomatic treatment of patients with cystic fibrosis (CF). Methods. The study included 100 patients aged 18 years and older with a confirmed diagnosis of CF, who were divided into two groups by stratified randomization in a ratio of 1 : 1 based on the initial level of FEV 1 (40–60% or > 60–100% from due value). Tigerase ® or Pulmozyme® were used in a dose of 2.5 mg daily, once a day in the form of inhalations using a jet nebulizer compressor for 24 weeks. Results and discussion: The analysis of the data regarding the primary efficacy endpoint – changes in FEV 1 – showed that in both groups (FAS population (Full analyses set) and PP population (Per protocol)), similar changes in FEV 1 were observed. The average value of changes in FEV 1 after 24 weeks of treatment compared with the initial level in the FAS population was –1.3% ± 9.8 % (95% CI (–4.1; 1.6)) in Group I (Tigerase ® ) and –1.9% ± 10.0% (95% CI (–4.7; 1.0)) in Group II (Pulmozyme ® ). The point estimate for the intergroup difference in changes in FEV 1 (Group I – Group II) was 0.6%. The calculated 95% CI for the difference in changes in FEV 1 in the FAS population was (–3.3; 4.6%]. In both populations studied, the intergroup difference in changes in FEV1 did not exceed 6%. During long-term treatment of patients with CF, no statistically significant differences were found in terms of efficacy (changes in FEV 1 and FVC; number of exacerbations of chronic pulmonary disease and the number of days before its development; change in body weight; quality of life) between medicinal products in both studied populations (FAS and PP). Conciusion. A safety analysis demonstrated the comparability of medicinal products in terms of the incidence of adverse events. The frequency of detection of antibodies to dornase alpha during the study was similar in the treatment groups; the formation of antibodies did not lead to a decrease in the efficacy and safety of therapy.