Background: BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. Methods: Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [− 20%; 20%]. Results: In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(− 8.05)-19.89%], thus, they lied within predetermined equivalence margins [− 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC 0-504 , С mах , Т max , T 1/2. Analysis of C trough did not reveal any significant inter-group differences as well.

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Background BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). Methods Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. Results In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures. Conclusions Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. Trial registration The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).

Цель исследования. Доказательство сходной эффективности препарата тимексон (BCD-063, глатирамера ацетат производства ЗАо «БиоКАД», россия) и копаксон-тева («Тева» фармацевтическое предприятие лТД, израиль) у пациентов с ремиттирующим рассеянным склерозом. Материал и методы. В многоцентровое двойное слепое плацебоконтролируемое сравнительное рандомизированное исследование iii фазы были включены 158 пациентов с достоверным диагнозом ремиттирующего рассеянного склероза. рандомизация в группы BCD-063, копаксон-тева и плацебо производилась в соотношении 2:2:1 соответственно. Результаты и заключение. При анализе эффективности после 48 недель терапии было установлено отсутствие различий между группами BCD-063 и копаксон-тева как на основании показателей МрТ, так и по частоте обострений заболевания. По результатам оценки первичной конечной точки (количества МрТ-подтвержденных обострений на пациента в год) среднее количество обострений в группе BCD-063 составило 0,098361 (0,351422), в группе копаксон-тева-0,098361 (0,351422), в группе плацебо-0,178571 (0,390021). результаты оценки по шкалам ЕDSS, MSfC также показали отсутствие различий между группой BCD-063 и группой препарата копаксон-тева. Был установлен благоприятный профиль безопасности как препарата BCD-063, так и копаксон-тева. Полученные данные свидетельствуют о терапевтической эквивалентности препарата BCD-063 (ЗАо «БиоКАД», россия) и препарата копаксон-тева, что является важным аспектом для дальнейшего внедрения воспроизведенного препарата глатирамера ацетата в практику лечения рассеянного склероза. Ключевые слова: ремиттирующий рассеянный склероз, глатирамера ацетат, BCD-063, тимексон. Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study

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