Comparative analysis of pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide-based drug for the treatment of obesity; [Сравнительное исследование фармакокинетических параметров, биоэквивалентности, безопасности, переносимости и иммуногенности лекарственного препарата для лечения ожирения на основе семаглутида]

One of the new classes of drugs for weight loss in overweight and obesity, the safety and efficacy of which have been proven in large-scale studies, are glucagon-like peptide-1 receptor agonists (GLP-1 agonists). Separately, it is worth highlighting the main representative from the GLP-1 agonists class, semaglutide. At a dose of 2.4 mg, this drug demonstrated clinically significant results in terms of the body weight reduction and improvement of cardiometabolic health. The aim of the work was to evaluate pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of the Velgia® (WRYC12301) at doses of 0.25 mg (0.68 mg/mL) and 2.4 mg (3.2 mg/mL) in comparison with the reference drug Wegovy® (Novo Nordisk A/S, Denmark) at the doses of 0.25 mg (0.68 mg/mL) and 2.4 mg (3.2 mg/mL). Materials and methods. The study was conducted between March and June 2024. The volunteers (n=60) were randomised into 4 groups (n=15 in each) in a 1:1 ratio to study the semaglutide dosages of 0.25 mg/dose (0.68 mg/mL) in Groups 1, 2 and 2.4 mg/dose (3.2 mg/mL) in Groups 3, 4. The study drug and the reference drug were injected subcutaneously into the anterior abdominal wall. Pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide (solution for subcutaneous administration, JSC Biochemik, Russia) were studied. Some parameters regulating the quality of the active pharmaceutical substance semaglutide, were determined. Results. The obtained 90% confidence intervals (CIs) for the ratio of Cmax and AUC(0-t) values of the study and reference drugs (Groups 1, 2) at a dose of 0.25 mg (0, 68 mg/mL) were 85.19–114.36% for Cmax and 81.35–112.60% for AUC(0-t), respectively, while for Groups 3, 4, at a dose of 2.4 mg (3.2 mg/mL), Cmax was 83.18–111.3% and AUC(0-t) was 91.70–120.89%, respectively. The obtained 90% CI lies within the established limits, which confirms the bioequivalence of the study and reference drugs. All adverse events registered during the study were of mild severity. According to the results of the immunogenicity parameters analysis, no antibodies to semaglutide were detected in the serum of volunteers. Conclusion. In the course of the study, the bioequivalence of the study and reference drugs was confirmed. A high safety profile and absence of immunogenicity were demonstrated for the Russian drug Velgia® (WRYC12301, semaglutide, solution for a subcutaneous administration, JSC Biochemik, Russia) in comparison with the reference drug (semaglutide, solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) in doses of 0.25 mg/dose (0.68 mg/mL) and 2.4 mg/dose (3.2 mg/mL). © А.С. Аметов, П.А. Белый, К.Я. Заславская, Е.А. Рогожина, В.С. Щербакова, Ю.Г. Казаишвили, А.В. Таганов, Т.Г. Бодрова, Е.С. Мищенко, К.Н. Корянова, Л.И. Щербакова, 2024.