Dataset Information

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.

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.

SUBMITTER: Blevins TC

PROVIDER: S-EPMC9649481 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Blevins Thomas C TC Raiter Yaron Y Sun Bin B Donnelly Charles C Shapiro Roxann R Chullikana Anoop A Rao Anita A Vashishta Laxmikant L Ranganna Gopinath G Barve Abhijit A

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20220917 6

<h4>Background</h4>MYL-1601D is a proposed biosimilar of originator insulin aspart, Novolog<sup>®</sup>/NovoRapid<sup>®</sup> (Ref-InsAsp-US/Ref-InsAsp-EU).<h4>Objective</h4>This study assessed the immunogenicity, efficacy, and safety of MYL-1601D with Ref-InsAsp-US in patients with type 1 diabetes mellitus (T1D).<h4>Methods</h4>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 (La ...[more]

PMID: 36114990

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Project description:IntroductionThe biosimilar SAR341402 insulin aspart (SAR-Asp) was compared to its originator NovoLog®/NovoRapid® insulin aspart (NN-Asp) in terms of efficacy, safety, and immunogenicity, in adults with type 1 or type 2 diabetes switching from different rapid-acting insulin analogs.MethodsThis phase 3, randomized, open-label, multinational, 52-week study (GEMELLI 1) enrolled participants with type 1 or type 2 diabetes (n = 597). At randomization, participants transitioned from NovoLog/NovoRapid (n = 380) or Humalog®/Liprolog® (n = 217) to equivalent (1:1) doses (or a dose at the discretion of the investigator) of either SAR-Asp or NN-Asp (1:1 randomization). Participants were treated with multiple daily injections in combination with insulin glargine 100 U/mL (Lantus®). In this subgroup analysis, efficacy measures (change in hemoglobin A1c [HbA1c], insulin dose [total, basal and mealtime]), and safety outcomes (hypoglycemia incidence, adverse events, anti-insulin aspart antibodies) of SAR-Asp were compared with those of NN-Asp separately according to the participants' prestudy mealtime insulin.ResultsAt week 26 (primary efficacy endpoint), change in HbA1c was similar between SAR-Asp and NN-Asp in those participants pre-treated with NovoLog/NovoRapid (least squares [LS] mean difference - 0.04%, 95% confidence interval [CI] - 0.182 to 0.106%) or Humalog/Liprolog (LS mean difference - 0.15%, 95% CI - 0.336 to 0.043%) (P value for treatment by subgroup interaction = 0.36). This HbA1c response persisted over the 52 weeks of the study similarly for both treatments within each subgroup. In both subgroups, changes in insulin doses were similar between treatments over 26 weeks and 52 weeks, as were the incidences of severe or any hypoglycemia, adverse events (including hypersensitivity and injection site reactions), and anti-insulin aspart antibodies.ConclusionsEfficacy and safety (including immunogenicity) profiles of SAR-Asp are similar to those of NN-Asp over 52 weeks in adults with diabetes irrespective of prior type of mealtime insulin.Trial registrationClinicalTrials.gov identifier: NCT03211858.

Project description:Background: SAR341402 (SAR-Asp) is a biosimilar/follow-on of the originator insulin aspart-NovoLog®/NovoRapid® (NN-Asp). This study investigated whether the efficacy, safety, and immunogenicity findings for SAR-Asp versus NN-Asp, observed over 6 months in people with type 1 (n = 497) or type 2 diabetes (n = 100) treated with multiple daily injections in combination with insulin glargine (Lantus®), are maintained after 12 months. Materials and Methods: GEMELLI 1 was a multicenter, randomized, open-label, phase 3 study. Participants completing the initial 6-month treatment period continued on SAR-Asp or NN-Asp, as randomized, for a 6-month safety extension. Results: Of the 597 participants randomized, 264 out of 301 (87.7%) and 263 out of 296 (88.9%) assigned to SAR-Asp and NN-Asp, respectively, completed 12 months of treatment. Improved glycemic control was sustained at 12 months in both treatment groups, with similar least-squares mean reductions in glycated hemoglobin (HbA1c) from baseline (SAR-Asp: -0.25%; NN-Asp: -0.26%). Fasting plasma glucose and seven-point self-monitored plasma glucose profile changes, including postprandial glucose excursions, and changes in mealtime and basal insulin dosages were similar between groups. Safety and tolerability, including anti-insulin aspart antibodies (AIAs; incidence, prevalence, titers, cross-reactivity to human insulin), neutralizing antibodies (incidence, prevalence), hypoglycemia, and treatment-emergent adverse events (including hypersensitivity events and injection site reactions), were similar between groups. No relationship was observed between maximum individual AIA titers and change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Conclusions: SAR-Asp and NN-Asp demonstrated similar efficacy and safety (including immunogenicity) in people with diabetes over 12 months of treatment.

Project description:BackgroundSAR341402 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.MethodsThis 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.ResultsOf 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.ConclusionsAlternating 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.

Project description:PurposeTo compare the immunogenicity and efficacy of insulin glargine biosimilar Ezelin (EZL) versus originator insulin glargine Lantus (LAN) as a reference basal insulin in patients with type 2 diabetes (T2D).Patients and methodsThis was a randomized, multicenter, open-label, 24-week study in insulin-naïve patients with T2D, with HbA1c of >7.0%. We randomly assigned 133 eligible patients to receive either EZL or LAN. Baseline characteristics, including insulin autoantibody (IAA), zinc transporter 8 (ZnT8) antibody, HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), AST, ALT, BUN, eGFR, and oral antidiabetic drugs, were obtained before starting insulin treatment. After starting treatment, insulin dose was titrated to achieve FPG target along with oral antidiabetic drugs. Patients were given home glucometer and assisted to record plasma glucose measurement and adverse event (AE). Every month, patients came to the diabetes clinic and performed a regular physical examination and intensifying treatment if needed. Out of the 133 randomized patients, only 122 completed the study and can be examined for their IAA and ZnT8 after 6 months of treatment. The study was registered in clinicaltrials.gov, NCT03352674.ResultsThere is a similar proportion of patients with changes of IAA from baseline: 1 out of 58 (1.7%) patients receiving EZL versus 1 out of 64 (1.6%) patients receiving LAN (p = 1.000). One patient in the EZL group (1.7%) versus none in the LAN group experienced a change of ZnT8 antibody from baseline. Similar glucose control in EZL versus LAN was determined by the change in HbA1c, FPG, and 2hPPG (-2.0%, -67.46 mg/dL, and -76.51 mg/dL in the EZL group versus -1.7%, -58.11 mg/dL, and -70.03 mg/dL in the LAN group). There were six events of documented hypoglycemia in the EZL group versus five events in the LAN group. No patients experienced diabetic ketoacidosis during the study.ConclusionOverall, insulin glargine biosimilar EZL and originator insulin glargine LAN have shown a similar immunogenicity profile, as well as efficacy in providing glucose control and safety findings in T2D populations.

Dataset Information

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.

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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Tweets

Dataset Information

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.

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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.