PMID- 38147290
OWN - NLM
STAT- Publisher
LR  - 20231226
IS  - 1720-8386 (Electronic)
IS  - 0391-4097 (Linking)
DP  - 2023 Dec 26
TI  - Comparative assessment of immunogenicity of recombinant insulin Aspart from 
      BioGenomics and its originator NovoRapid(R) in adult patients with type 2 diabetes 
      mellitus.
LID - 10.1007/s40618-023-02263-5 [doi]
AB  - OBJECTIVES: To assess and compare the immunogenicity of recombinant Insulin 
      Aspart [manufactured by BioGenomics Limited (BGL-ASP)] with its originator 
      NovoRapid(R) (manufactured by Novo Nordisk) in adult patients with type 2 diabetes 
      mellitus. RESEARCH DESIGN AND METHODS: BGL-IA-CTP301 study was a randomized, open 
      label, parallel group, multicenter phase-III clinical study to compare the 
      efficacy and safety of recombinant Insulin Aspart 100 U/mL [manufactured by 
      BioGenomics Limited (BGL-ASP)] with its reference medicinal product (RMP); 
      NovoRapid(R) [manufactured by Novo Nordisk], in adult patients with Type 2 diabetes 
      mellitus (T2DM). The primary objective of the study was to compare the 
      immunogenicity of BGL-ASP and RMP; NovoRapid(R) in patient serum samples collected 
      from phase-III clinical study. Immunogenicity was studied as the incidence of 
      patients positive for anti-insulin Aspart (AIA) antibodies, developed against 
      BGL-ASP/RMP at baseline, end of 12 week and end of 24 week of the treatment 
      period. The changes in incidence of patients positive for AIA antibodies 
      post-baseline were also studied to assess and compare the treatment-emergent 
      antibody response (TEAR) between the treatment groups (BGL-ASP and RMP). 
      Statistical evaluation was done by Fisher's exact test to compare the overall 
      incidence of patients positive for AIA antibodies and the TEAR positives observed 
      post-baseline in both the treated groups. An in-vitro neutralizing antibody assay 
      (Nab assay) was also performed to study the effect of AIA antibodies in 
      neutralizing the biological activity/metabolic function of the insulin. The 
      neutralizing potential of AIA was studied by its effect on %glucose uptake. We 
      also evaluated the association between AIA antibody levels and its impact on 
      biological activity by studying the correlation between them. RESULTS: Analysis 
      of immunogenicity data suggested that the percentage of patients positive for AIA 
      antibodies until week 24 was similar and comparable in both the treatment groups, 
      BGL-ASP and RMP; NovoRapid(R). The changes in incidence of patients positive for 
      AIA post-baseline in terms of TEAR positives were also similar and comparable 
      between the treatment groups. The results of the Nab assay with confirmed 
      positive AIA samples from BGL-ASP- and RMP-treated groups did not have any 
      negative impact on %glucose uptake by the cells in Nab assay, confirming the 
      absence of neutralizing antibodies in both the treatment groups. The correlation 
      studies also showed absence of association between AIA antibody levels and 
      percentage glucose uptake in both BGL-ASP and RMP-NovoRapid(R) treatment groups(.) 
      CONCLUSIONS: The immunogenicity assessment based on the overall incidence of 
      patients positive for AIA, changes in incidence of patients positive for AIA 
      post-baseline, TEAR rates and absence of neutralizing antibodies, were found to 
      be apparently similar and comparable in both the treatment groups (BGL-ASP and 
      RMP). We conclude from our studies that the immunogenicity of BGL-ASP is similar 
      and comparable to RMP and the observed immunogenicity in terms of anti-insulin 
      Aspart antibody levels had no impact on the biological activity of insulin.
CI  - (c) 2023. The Author(s), under exclusive licence to Italian Society of 
      Endocrinology (SIE).
FAU - Mishra, A
AU  - Mishra A
AD  - BioGenomics Ltd, Thane, India. akshay.mishra@biogenomics.co.in.
FAU - Dongre, S
AU  - Dongre S
AD  - BioGenomics Ltd, Thane, India.
FAU - Kulkarni, G
AU  - Kulkarni G
AD  - BioGenomics Ltd, Thane, India.
FAU - Deshmane, R
AU  - Deshmane R
AD  - BioGenomics Ltd, Thane, India.
FAU - Thappa, D
AU  - Thappa D
AD  - BioGenomics Ltd, Thane, India.
FAU - Ghade, N
AU  - Ghade N
AD  - BioGenomics Ltd, Thane, India.
FAU - Lona, J
AU  - Lona J
AD  - BioGenomics Ltd, Thane, India.
FAU - Kokatam, S
AU  - Kokatam S
AD  - BioGenomics Ltd, Thane, India.
FAU - Deo, A
AU  - Deo A
AD  - BioGenomics Ltd, Thane, India.
FAU - Sonar, S
AU  - Sonar S
AD  - BioGenomics Ltd, Thane, India.
FAU - Krishnan, A
AU  - Krishnan A
AD  - BioGenomics Ltd, Thane, India.
LA  - eng
PT  - Journal Article
DEP - 20231226
PL  - Italy
TA  - J Endocrinol Invest
JT  - Journal of endocrinological investigation
JID - 7806594
SB  - IM
OTO - NOTNLM
OT  - Anti-insulin aspart antibodies
OT  - Biosimilars
OT  - Glucose uptake
OT  - Immunogenicity
OT  - Neutralizing antibodies
OT  - Treatment emergent antibody response
EDAT- 2023/12/26 12:42
MHDA- 2023/12/26 12:42
CRDT- 2023/12/26 11:11
PHST- 2023/09/14 00:00 [received]
PHST- 2023/11/28 00:00 [accepted]
PHST- 2023/12/26 12:42 [medline]
PHST- 2023/12/26 12:42 [pubmed]
PHST- 2023/12/26 11:11 [entrez]
AID - 10.1007/s40618-023-02263-5 [pii]
AID - 10.1007/s40618-023-02263-5 [doi]
PST - aheadofprint
SO  - J Endocrinol Invest. 2023 Dec 26. doi: 10.1007/s40618-023-02263-5.