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

Thomas C Blevins, Yaron Raiter, Bin Sun, Charles Donnelly, Roxann Shapiro, Anoop Chullikana, Anita Rao, Laxmikant Vashishta, Gopinath Ranganna, Abhijit Barve, Thomas C Blevins, Yaron Raiter, Bin Sun, Charles Donnelly, Roxann Shapiro, Anoop Chullikana, Anita Rao, Laxmikant Vashishta, Gopinath Ranganna, Abhijit Barve

Abstract

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.

Conflict of interest statement

Thomas C. Blevins has received clinical research support from AstraZeneca, Eli Lilly, Lexicon, Merck, Mylan, Novo Nordisk, Sanofi, Mannkind, Medtronic, and Tandem and speaker fees from Amgen, AstraZeneca, Boehringer-Ingelheim, Janssen, Eli Lilly, Merck, Novo Nordisk, and Sanofi. Bin Sun, Charles Donnelly, Roxann Shapiro, Gopinath Ranganna, and Abhijit Barve are employees of Viatris Inc. and may hold stock or stock options in the company. Yaron Raiter is an ex-employee of Viatris Inc and currently associated with GE Healthcare. Anoop Chullikana and Anita Rao are Biocon Biologics Ltd employees and may hold stock or stock options in the company. Laxmikant Vashishta is an ex-employee of Biocon Biologics Ltd. and currently a full-time employee of Alvogen Pharma India Pvt. Ltd.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Means and standard deviations for observed A HbA1c (%) values over time, B fasting plasma glucose (mmol/L) values over time by treatment, C daily mealtime insulin dose (U/kg) values over time by treatment, D total daily insulin dose (U/kg). Means and standard deviations are from descriptive statistics procedure. In addition to the current product name Novolog®, the product code name Ref-InsAsp-US is used throughout the document. HbA1c glycated hemoglobin, N number of patients in population, SD standard deviation
Fig. 1
Fig. 1
Means and standard deviations for observed A HbA1c (%) values over time, B fasting plasma glucose (mmol/L) values over time by treatment, C daily mealtime insulin dose (U/kg) values over time by treatment, D total daily insulin dose (U/kg). Means and standard deviations are from descriptive statistics procedure. In addition to the current product name Novolog®, the product code name Ref-InsAsp-US is used throughout the document. HbA1c glycated hemoglobin, N number of patients in population, SD standard deviation
Fig. 2
Fig. 2
Means and standard deviations for hypoglycemic event rates (episodes per 30 days adjusted). Hypoglycemia was defined as a state produced by a lower-than-normal level of glucose in the blood. In both treatment groups, the greatest reduction from baseline in hypoglycemic event rates was observed between baseline and week 12. Note: in addition to the current product name Novolog®, the product code name Ref-InsAsp-US is used throughout the document. N number of patients in the population, SD standard deviation

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Source: PubMed

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