Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Aspart (MYL-1601D) Compared with Originator Insulin Aspart (Novolog®) in Patients with Type 1 Diabetes After 24 Weeks: A Randomized Open-Label Study,BioDrugs

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Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Aspart (MYL-1601D) Compared with Originator Insulin Aspart (Novolog®) in Patients with Type 1 Diabetes After 24 Weeks: A Randomized Open-Label Study
BioDrugs ( IF 5.4 ) Pub Date : 2022-09-17 , DOI: 10.1007/s40259-022-00554-6
Thomas C Blevins ₁ , Yaron Raiter ₂ , Bin Sun ₃ , Charles Donnelly ₃ , Roxann Shapiro ₃ , Anoop Chullikana ₄ , Anita Rao ₄ , Laxmikant Vashishta ₅ , Gopinath Ranganna ₆ , Abhijit Barve ₃

Affiliation

Background

MYL-1601D is a proposed biosimilar of originator insulin aspart, Novolog^®/NovoRapid^® (Ref-InsAsp-US/Ref-InsAsp-EU).

Objective

This study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D).

Methods

This was a 24-week, open-label, randomized, phase III study. Patients were randomized 1:1 to mealtime MYL-1601D or Ref-InsAsp-US in combination with insulin glargine (Lantus SoloSTAR^®) once daily. The treatment-emergent antibody response (TEAR) rate (defined as patients who were anti-insulin antibody [AIA] negative at baseline and became positive at any timepoint post-baseline or patients who were AIA positive at baseline and demonstrated a 4-fold increase in titer values at any timepoint post-baseline) was the primary endpoint. The study also compared the change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), prandial, basal, and total daily insulin, 7-point self-monitored blood glucose (SMBG) profiles, immunogenicity, and adverse events (AEs) including hypoglycemia.

Results

In total, 478 patients were included in the intent-to-treat analysis (MYL-1601D: 238; Ref-InsAsp-US: 240) set. The 90% confidence interval (CI) for the primary endpoint was within the pre-defined equivalence margin of ±11.7% and the treatment differences (SE) in TEAR responders between the treatment groups was − 2.86 (4.16) with 90% CI − 9.71 to 3.99. The mean (SD) changes from baseline for HbA1c, FPG, and insulin dosages were similar in both groups at week 24. The safety profiles including hypoglycemia, immune-related events, AEs, and other reported variables were similar between the treatment groups at week 24.

Conclusions

MYL-1601D demonstrated similar immunogenicity, efficacy, and safety profiles to Ref-InsAsp-US in patients with T1D over 24 weeks.

Clinical Trial Registration ClinicalTrials.gov:

NCT03760068.

中文翻译：

24 周后，门冬胰岛素生物仿制药 (MYL-1601D) 与原研门冬胰岛素 (Novolog®) 相比在 1 型糖尿病患者中的免疫原性、功效和安全性：一项随机开放标签研究

背景

MYL-1601D 是原研门冬胰岛素 Novolog ^® /NovoRapid ^® (Ref-InsAsp-US/Ref-InsAsp-EU) 的拟议生物仿制药。

客观的

本研究评估了 MYL-1601D 与 Ref-InsAsp-US 在 1 型糖尿病 (T1D) 患者中的免疫原性、有效性和安全性。

方法

这是一项为期 24 周的开放标签随机 III 期研究。患者按 1:1 的比例随机分配至进餐时间 MYL-1601D 或 Ref-InsAsp-US 联合甘精胰岛素 (Lantus SoloSTAR ^® )，每日一次。治疗出现的抗体反应 (TEAR) 率（定义为基线时抗胰岛素抗体 [AIA] 阴性但在基线后任何时间点变为阳性的患者或基线时 AIA 阳性且增加 4 倍的患者基线后任何时间点的滴度值）是主要终点。该研究还比较了糖化血红蛋白 (HbA1c)、空腹血糖 (FPG)、膳食胰岛素、基础胰岛素和每日总胰岛素、7 点自我监测血糖 (SMBG) 概况、免疫原性和不良事件相对于基线的变化。 AEs）包括低血糖。

结果

总共有 478 名患者被纳入意向治疗分析（MYL-1601D：238；Ref-InsAsp-US：240）组。主要终点的 90% 置信区间 (CI) 在 ±11.7% 的预定义等效界值内，治疗组之间 TEAR 反应者的治疗差异 (SE) 为 − 2.86 (4.16)，90% CI 为 − 9.71到 3.99。第 24 周时，两组的 HbA1c、FPG 和胰岛素剂量相对于基线的平均 (SD) 变化相似。包括低血糖、免疫相关事件、AE 和其他报告变量在内的安全性特征在第 2 周时在治疗组之间相似24.