[The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial].

ABSTRACT

AIM: To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). MATERIALS AND METHODS: Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (11) into 2 treatment groups investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve LDH concentrationtime (AUCLDH) throughout the study period weeks 527. RESULTS: The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/ldays. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9146 500.9] U/ldays and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups. CONCLUSION: The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.