Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial

Viral N Shah; Amer Al-Karadsheh; Cathy Barnes; Jose Mandry; Samer Nakhle; Karin Wernicke-Panten; Daniel Kramer; Wolfgang Schmider; Suzanne Pierre; Lenore Teichert; Baerbel Rotthaeuser; Bhaswati Mukherjee; Timothy S Bailey

doi:10.1177/19322968241232709

Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial

J Diabetes Sci Technol. 2024 Feb 29:19322968241232709. doi: 10.1177/19322968241232709. Online ahead of print.

Authors

Viral N Shah^{1

2}, Amer Al-Karadsheh³, Cathy Barnes⁴, Jose Mandry⁵, Samer Nakhle⁶, Karin Wernicke-Panten⁷, Daniel Kramer⁷, Wolfgang Schmider⁷, Suzanne Pierre⁸, Lenore Teichert⁷, Baerbel Rotthaeuser⁷, Bhaswati Mukherjee⁹, Timothy S Bailey¹⁰

Affiliations

¹ Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
² Division of Endocrinology and Metabolism and Center for Diabetes and Metabolic Diseases, Indiana University, Indianapolis, IN, USA.
³ The Endocrine Center, Houston, TX, USA.
⁴ Suncoast Clinical Research, New Port Richey, FL, USA.
⁵ West Orange Endocrinology, Ococee, FL, USA.
⁶ Palm Medical Group, Las Vegas, NV, USA.
⁷ Sanofi, Frankfurt am Main, Germany.
⁸ Sanofi, Chilly-Mazarin, France.
⁹ Sanofi, Gentilly, France.
¹⁰ AMCR Institute, Escondido, CA, USA.

PMID: 38420944
DOI: 10.1177/19322968241232709

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: GEMELLI X; SAR341402; biosimilar; insulin aspart; interchangeable.