Abstract
Background. Gaucher disease (GD) is a rare hereditary condition, which represents the most common form of lysosomal storage diseases. Enzyme replacement therapy (ERT) with recombinant glucocerebrosidase is used for the treatment of type 1 and type 3 GD. Imiglucerase (recombinant glucocerebrosidase) is the first biotechnological ERT medication possessing confirmed clinical efficacy and safety.Aim. To compare the efficacy and safety of the biosimilar drug Glurazyme and the reference drug Cerezyme during ERT therapy in patients with type 1 GD.Materials and methods. Thirty patients aged from 19 to 63 years (33 ± 9.7 years) with a stable course of type 1 GD were enrolled in the study. The patients were randomly divided into two equal treatment groups, one of which received Glurazyme and the other received the reference drug Cerezyme. In both groups, the drugs were used in doses of 15–40 U/kg intravenously once every 14 days for 52 weeks.Results. At the end of the study, at week 52 (primary endpoint of efficacy), both groups demonstrated a similar increase in hemoglobin concentration compared to the baseline data. In both groups, the average increase in hemoglobin concentration was 4.8 g/l, with this parameter varying between the groups by 0.1 g/l. At week 52, the calculated 95% confidence interval for the difference in hemoglobin concentration did not cross the non-inferiority margin of 18 g/l, which had been specified as the lower level of drug efficacy. This led to the conclusion that the studied drug Glurazyme is not inferior to Cerezyme in terms of efficacy. A comparison of the treatment groups by secondary endpoints of efficacy revealed: no decrease in hemoglobin concentration by more than 20 % in both groups; no differences between the groups by the number of patients with a change in platelet concentration relative to the baseline values; no increase in the spleen and liver volume by more than 20 and 10 %, respectively, in both groups. The doses of the drug under study and the reference drug remained unchanged during the research. The concentration of chemokine CCL-18 decreased slightly in 10 patients (64.3 %) and 6 patients (40 %) in the Glurazyme group and the Cerezyme group, respectively. The proportion of patients with improved physical and mental health components was 57.1 and 57.1 %, respectively, in the Glurazyme group compared to 73.3 and 60 %, respectively, in the Cerezyme group. Changes in the state of the bone tissue and the reserves of accumulated metabolites in the bone marrow showed a similar decrease in the severity of bone marrow infiltration in both groups.Conclusions. Glurazyme and Cerezyme showed comparable parameters of efficacy and safety in patients with GD type 1 during long-term enzyme replacement therapy.
Highlights
Gaucher disease (GD) is a rare hereditary condition, which represents the most common form of lysosomal storage diseases
Note. 1,2 — the diagnosis of Gaucher disease was confirmed by medical history data: the low activity of β-glucocerebrosidase in leukocytes in 25 patients and / or the presence of the gene mutation encoding β-glucocerebrosidase in 3 of 8 patients; for the rest of the patients data were not available; 3 — data on the spleen volume were not available for 4 patients in the Glurazyme group and for 6 patients in the Cerezyme group due to the previously conducted splenectomy
Обследование больных на 52-й неделе лечения не выявило ни одного больного со снижением концентрации гемоглобина крови более чем на 20 % от исходных значений
Summary
Glurazyme and Cerezyme showed comparable parameters of efficacy and safety in patients with GD type 1 during long-term enzyme replacement therapy. В связи с этим создание новых лекарственных препаратов, в том числе биоаналогов рекомбинантной глюкоцереброзидазы для лечения БГ, является актуальной задачей. Развитие фармацевтического производства биоаналогов оригинальных лекарственных препаратов для лечения редких заболеваний является одним из ведущих направлений фармацевтической промышленности Российской Федерации в соответствии со стратегией «Фарма-2020». Согласно регуляторным требованиям ЕАЭС, утвержденным Советом Евразийской экономической комиссии 03.11.2016, разработка биоаналога на всех этапах требует проведения сравнительных с оригинальным (референтным) препаратом исследований, в ходе которых изучаются доказательства эквивалентности препаратов по физико-химическим параметрам, доклиническим данным, фармакокинетике (ФК), фармакодинамике (ФД), эффективности, безопасности и иммуногенности. Полученные доказательства фармакокинетической эквивалентности препаратов Глуразим и Церезим, а также хорошей переносимости и благоприятного профиля безопасности препарата Глуразим явились основанием для проведения сравнительного клинического исследования II–III фазы [22]. Цель исследования — сравнить эффективность и безопасность препаратов Глуразим и Церезим при проведении ЗФТ у больных БГ 1-го типа
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