Shah Viral N, Al-Karadsheh Amer, Barnes Cathy, Mandry Jose, Nakhle Samer, Wernicke-Panten Karin, Kramer Daniel, Schmider Wolfgang, Pierre Suzanne, Teichert Lenore, Rotthaeuser Baerbel, Mukherjee Bhaswati, Bailey Timothy S
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Division of Endocrinology and Metabolism and Center for Diabetes and Metabolic Diseases, Indiana University, Indianapolis, IN, USA.
J Diabetes Sci Technol. 2024 Feb 29:19322968241232709. doi: 10.1177/19322968241232709.
SAR341402 insulin aspart (SAR-Asp) is a rapid-acting insulin analog developed as an interchangeable biosimilar to the marketed insulin aspart reference product (NovoLog; NN-Asp). GEMELLI X was a randomized controlled trial to assess outcomes with a biosimilar in line with the US Food and Drug Administration requirements for designation as an interchangeable biosimilar. This report assessed whether multiple switches between SAR-Asp and NN-Asp lead to equivalent safety and efficacy compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D) treated with multiple daily injections, using once-daily insulin glargine U100 (Lantus) as the basal insulin.
This open-label randomized (1:1), parallel-group, phase 3 trial compared four × four weeks of alternating use of individually titrated SAR-Asp and NN-Asp (NN-Asp for first four weeks, SAR-Asp in last four weeks; switching group) vs 16 weeks of continuous use of NN-Asp (nonswitching group). End points included pharmacokinetics, immunogenicity, adverse events, hypoglycemia, insulin dose, and change in efficacy parameters.
Of the 210 patients randomized, 200 (95.5%) completed the trial. Patients assigned to switching group (n = 104) and nonswitching group (n = 106) showed similar safety and tolerability, including anti-insulin aspart antibody responses, adverse events, and hypoglycemia. At week 16, there was no relevant difference between switching vs nonswitching groups in the change from baseline in glycated hemoglobin (least square [LS] mean difference = 0.05% [95% confidence interval [CI] = -0.13, 0.22]; 0.50 mmol/mol [-1.40, 2.39]), fasting plasma glucose (LS mean difference = 0.23 mmol/L [95% CI = -1.08, 1.53]; 4.12 mg/dL [-19.38, 27.62]), and changes in insulin dosages.
Alternating doses of SAR-Asp and NN-Asp compared with continuous use of NN-Asp showed similar safety, immunogenicity, and clinical efficacy in adults with T1D. This study supports interchangeability between SAR-Asp and NN-Asp in T1D management.
SAR341402门冬胰岛素（SAR-Asp）是一种速效胰岛素类似物，作为可互换生物类似药开发，与已上市的门冬胰岛素参比产品（诺和锐；NN-Asp）相似。GEMELLI X是一项随机对照试验，旨在根据美国食品药品监督管理局对可互换生物类似药认定的要求，评估一种生物类似药的疗效。本报告评估了在使用每日一次甘精胰岛素U100（来得时）作为基础胰岛素进行多次皮下注射治疗的1型糖尿病（T1D）成人患者中，与持续使用NN-Asp相比，SAR-Asp和NN-Asp之间多次转换是否会导致等效的安全性和疗效。
这项开放标签、随机（1:1）、平行组3期试验比较了四周内分别滴定的SAR-Asp和NN-Asp交替使用（前四周使用NN-Asp，后四周使用SAR-Asp；转换组）与连续使用NN-Asp 16周（非转换组）的情况。终点包括药代动力学、免疫原性、不良事件、低血糖、胰岛素剂量以及疗效参数的变化。
随机分组的210例患者中，200例（95.5%）完成了试验。分配至转换组（n = 104）和非转换组（n = 106）的患者显示出相似的安全性和耐受性，包括抗门冬胰岛素抗体反应、不良事件和低血糖。在第16周时，转换组与非转换组之间糖化血红蛋白自基线的变化（最小二乘[LS]均值差异 = 0.05% [95%置信区间[CI] = -0.13, 0.22]；0.50 mmol/mol [-1.40, 2.39]）、空腹血糖（LS均值差异 = 0.23 mmol/L [95% CI = -1.08, 1.53]；4.12 mg/dL [-19.38, 27.62]）以及胰岛素剂量变化均无显著差异。
与持续使用NN-Asp相比，交替使用SAR-Asp和NN-Asp在T1D成人患者中显示出相似的安全性、免疫原性和临床疗效。本研究支持在T1D管理中SAR-Asp和NN-Asp的可互换性。
