PMID- 36114990
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20221207
IS  - 1179-190X (Electronic)
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 36
IP  - 6
DP  - 2022 Nov
TI  - Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Aspart (MYL-1601D) 
      Compared with Originator Insulin Aspart (Novolog((R))) in Patients with Type 1 
      Diabetes After 24 Weeks: A Randomized Open-Label Study.
PG  - 761-772
LID - 10.1007/s40259-022-00554-6 [doi]
AB  - BACKGROUND: MYL-1601D is a proposed biosimilar of originator insulin aspart, 
      Novolog((R))/NovoRapid((R)) (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((R))) 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.
CI  - (c) 2022. The Author(s).
FAU - Blevins, Thomas C
AU  - Blevins TC
AD  - Texas Diabetes and Endocrinology, Austin, Texas, USA.
FAU - Raiter, Yaron
AU  - Raiter Y
AD  - GE Healthcare, Eindhoven, The Netherlands.
FAU - Sun, Bin
AU  - Sun B
AD  - Viatris Inc., Canonsburg, PA, USA.
FAU - Donnelly, Charles
AU  - Donnelly C
AD  - Viatris Inc., Canonsburg, PA, USA.
FAU - Shapiro, Roxann
AU  - Shapiro R
AD  - Viatris Inc., Canonsburg, PA, USA.
FAU - Chullikana, Anoop
AU  - Chullikana A
AD  - Biocon Research Limited, Bengaluru, India.
FAU - Rao, Anita
AU  - Rao A
AD  - Biocon Research Limited, Bengaluru, India.
FAU - Vashishta, Laxmikant
AU  - Vashishta L
AD  - Alvogen Pharma India Pvt. Ltd, Bengaluru, India.
FAU - Ranganna, Gopinath
AU  - Ranganna G
AUID- ORCID: 0000-0001-9974-3354
AD  - Viatris, Bengaluru, India. gopi.ranganna@viatris.com.
FAU - Barve, Abhijit
AU  - Barve A
AD  - Viatris Inc., Canonsburg, PA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03760068
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220917
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
RN  - D933668QVX (Insulin Aspart)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Blood Glucose)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - 0 (Insulin)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 1/drug therapy
MH  - Insulin Aspart/adverse effects
MH  - Glycated Hemoglobin/analysis/therapeutic use
MH  - *Biosimilar Pharmaceuticals/adverse effects
MH  - Hypoglycemic Agents/adverse effects
MH  - Blood Glucose
MH  - Insulin Glargine/adverse effects
MH  - *Hypoglycemia/chemically induced
MH  - Insulin/adverse effects
PMC - PMC9649481
COIS- 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.
EDAT- 2022/09/18 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/09/17
CRDT- 2022/09/17 11:18
PHST- 2022/08/23 00:00 [accepted]
PHST- 2022/09/18 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/09/17 11:18 [entrez]
PHST- 2022/09/17 00:00 [pmc-release]
AID - 10.1007/s40259-022-00554-6 [pii]
AID - 554 [pii]
AID - 10.1007/s40259-022-00554-6 [doi]
PST - ppublish
SO  - BioDrugs. 2022 Nov;36(6):761-772. doi: 10.1007/s40259-022-00554-6. Epub 2022 Sep 
      17.