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

Date: Sep 17th, 2022

Link: https://link.springer.com/article/10.1007/s40259-022-00554-6

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.

Funding: The study was sponsored by Mylan GmbH, Switzerland (now Viatris), and Biocon Biologics Ltd, Bengaluru, India.

Authors: Ulrike Hövelmann MD, Yaron Raiter MD, Anoop Chullikana MD, Mark Liu PhD, Charles Donnelly PhD, Tracey Lawrence PhD, Nilanjan Sengupta PhD, Gopu CL PhD, Gopinath Ranganna FFPM, Abhijit Barve MD

Date: Aug 11th, 2021

Link: https://doi.org/10.1111/dom.14519

Abstract –

Aim: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL-1601D biosimilar with originator, NovoLog (Ref-InsAsp-US), and NovoRapid (Ref-InsAsp-EU).

Materials and Methods: This was a double-blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration-time curve from 0 to 12 hours (AUC0-12h) and maximum plasma insulin aspart concentration (Cmax). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUCGIR0-12h) and maximum GIR (GIRmax). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS-mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL-1601D vs. Ref-InsAsp-US) and 95% CIs (MYL-1601D vs. Ref-InsAsp-EU) of primary PD variables, were to be within 80% to 125% to show BE.

Results: MYL-1601D showed PK BE to both Ref-InsAsp-US (AUC0-12h geometric LS-mean ratio 102.17, 90% CI [100.26; 104.11]; Cmax 106.13 [100.71; 111.85]) and Ref-InsAsp-EU (AUC0-12h 101.84 [100.04; 103.67]; Cmax 105.74 [101.09; 110.60]). Likewise, MYL-1601D showed PD BE to Ref-InsAsp-US (AUCGIR_0-last 99.93; 90% CI [95.74; 104.30]; GIR_max 100.12 [94.46; 106.12]) and Ref-InsAsp-EU (AUCGIR_0-last 96.42; 95% CI [91.17; 101.98]; GIR_max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated.

Conclusion: MYL-1601D showed BE to Ref-InsAsp-US and Ref-InsAsp-EU with a comparable safety profile.

Conflict of Interest: UH is an employee of Profil. YR, ML, CD, TL, GR, and AB are employees of Viatris Inc. and may hold stock or stock options in the company. GCL, AC, and NS are Biocon Biologics Ltd employees and may hold stock or stock options in the company.