Viatris Inc, 1000 Mylan Boulevard, Canonsburg, PA, 15317, USA.
Biocon Research Limited, 20th KM, Hosur Road, Electronic City, 560100, Bangalore, India.
BMC Endocr Disord. 2021 Jun 26;21(1):129. doi: 10.1186/s12902-021-00797-4.
MYL-1501D is a proposed biosimilar to insulin glargine. The noninferiority of MYL-1501D was demonstrated in patients with type 1 diabetes and type 2 diabetes in 2 phase 3 trials. Immunogenicity of MYL-1501D and reference insulin glargine was examined in both studies.
INSTRIDE 1 and INSTRIDE 2 were multicenter, open-label, randomized, parallel-group studies. In INSTRIDE 1, patients with type 1 diabetes received MYL-1501D or insulin glargine over a 52-week period. In INSTRIDE 2, patients with type 2 diabetes treated with oral antidiabetic drugs, insulin naive or not, received MYL-1501D or reference insulin glargine over a 24-week period. Incidence rates and change from baseline in relative levels of antidrug antibodies (ADA) and anti-host cell protein (anti-HCP) antibodies in both treatment groups were determined by a radioimmunoprecipitation assay and a bridging immunoassay, respectively. Results were analyzed using a mixed-effects model (INSTRIDE 1) or a nonparametric Wilcoxon rank sum test (INSTRIDE 2).
Total enrollment was 558 patients in INSTRIDE 1 and 560 patients in INSTRIDE 2. The incidence of total and cross-reactive ADA was comparable between treatment groups in INSTRIDE 1 and INSTRIDE 2 (P > 0.05 for both). A similar proportion of patients had anti-HCP antibodies in both treatment groups in INSTRIDE 1 at week 52 (MYL-1501D, 93.9 %; reference insulin glargine, 89.6 %; P = 0.213) and in INSTRIDE 2 at week 24 (MYL-1501D, 87.3 %; reference insulin glargine, 86.9 %; P > 0.999).
In INSTRIDE 1 and INSTRIDE 2, similar immunogenicity profiles were observed for MYL-1501D and reference insulin glargine in patients with type 1 diabetes and type 2 diabetes, respectively.
ClinicalTrials.gov, INSTRIDE 1 ( NCT02227862 ; date of registration, August 28, 2014); INSTRIDE 2 ( NCT02227875 ; date of registration, August 28, 2014).
MYL-1501D 是一种拟用于治疗胰岛素的生物类似药。在两项 3 期临床试验中，1 型糖尿病和 2 型糖尿病患者的研究结果显示 MYL-1501D 非劣效于胰岛素 glargine。在这两项研究中，均对 MYL-1501D 和参考胰岛素 glargine 的免疫原性进行了检测。
INSTRIDE 1 和 INSTRIDE 2 是两项多中心、开放性、随机、平行分组的研究。在 INSTRIDE 1 中，1 型糖尿病患者接受 MYL-1501D 或胰岛素 glargine 治疗，为期 52 周。在 INSTRIDE 2 中，接受口服抗糖尿病药物治疗、无论是否使用胰岛素的 2 型糖尿病患者接受 MYL-1501D 或参考胰岛素 glargine 治疗，为期 24 周。通过放射免疫沉淀测定法和桥接免疫测定法，分别确定两组患者抗药物抗体（ADA）和抗宿主细胞蛋白（anti-HCP）抗体相对水平的发生率和从基线的变化。使用混合效应模型（INSTRIDE 1）或非参数 Wilcoxon 秩和检验（INSTRIDE 2）进行分析。
INSTRIDE 1 共纳入 558 例患者，INSTRIDE 2 共纳入 560 例患者。在 INSTRIDE 1 和 INSTRIDE 2 中，治疗组间总 ADA 和交叉反应性 ADA 的发生率相似（均 P > 0.05）。在 INSTRIDE 1 的第 52 周（MYL-1501D，93.9%；参考胰岛素 glargine，89.6%；P = 0.213）和 INSTRIDE 2 的第 24 周（MYL-1501D，87.3%；参考胰岛素 glargine，86.9%；P > 0.999），两组患者均有相似比例的患者出现抗-HCP 抗体。
在 1 型糖尿病和 2 型糖尿病患者中，INSTRIDE 1 和 INSTRIDE 2 研究中，MYL-1501D 和参考胰岛素 glargine 的免疫原性特征相似。
ClinicalTrials.gov，INSTRIDE 1（NCT02227862；注册日期，2014 年 8 月 28 日）；INSTRIDE 2（NCT02227875；注册日期，2014 年 8 月 28 日）。
