Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration–time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration–time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056

Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab. Aim.To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH. Materials and methods.The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks. Results.During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity. Conclusion.The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.

Метою дослідження було вивчити динаміку змін гормональних показників оваріального резерву при серійному застосуванні циклофосфаміду в експерименті. Досліди проводили на 45 статевозрілих самицях білих щурів. Вивчали рівні антимюллерового гормону, естрадіолу та фолікулостимулюючого гормону. Загалом проводили 4 курси хіміотерапії з інтервалом 3 тижні. Після кожного курсу хіміотерапії двічі вивчали гормональний статус піддослідних тварин: під час першого проеструсу після проведеного курсу (для визначення гострої оваріальної токсичності введеного препарату) та під час останнього проеструсу перед черговим курсом хіміотерапії (для вивчення відновлення функції яєчників). Динаміка рівнів гормональних показників оваріального резерву при серійному введенні циклофосфаміду характеризувалася хвилеподібною динамікою із погіршенням показників безпосередньо після курсу хіміотерапії та частковим їх відновленням протягом періоду між суміжними курсами. Оваріотоксичність циклофосфаміду при серійному введенні в терапевтичних дозах в експерименті проявлялася достовірними змінами рівнів антимюллерового гормону, естрадіолу та фолікулостимулюючого гормону вже після проведення першого курсу хіміотерапії.Ключові слова: циклофосфамід, антимюллерів гормон, естрадіол, фолікулостимулюючий гормон, щури.