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. 2023 Dec;23(4):421-438.
doi: 10.1007/s40268-023-00441-7. Epub 2023 Oct 13.

Analytical and Functional Similarity of the Biosimilar Candidate ABP 654 to Ustekinumab Reference Product

Greg Cantin  1 , Qian Liu  2 , Bhavana Shah  2 , Scott Kuhns  2 , Mats Wikström  2 , Shawn Cao  2 , Jennifer Liu  2
Affiliations

Analytical and Functional Similarity of the Biosimilar Candidate ABP 654 to Ustekinumab Reference Product

Greg Cantin et al. Drugs R D. 2023 Dec.

Abstract

Background and objective: ABP 654 is a proposed biosimilar to ustekinumab reference product (RP), a human immunoglobulin isotype class G subclass 1 kappa monoclonal antibody that acts as an antagonist of interleukin (IL)-23 and IL-12. Ustekinumab RP is indicated for the treatment of some forms of plaque psoriasis, active psoriatic arthritis, Crohn's disease, and ulcerative colitis. ABP 654 and ustekinumab RP utilize different expression systems, and the purpose of this study was to assess analytical similarity between ABP 654 and ustekinumab RP sourced from the United States (US) and the European Union (EU).

Methods: The analytical testing plan included general properties, primary structure, higher-order structure, product-related substances and impurities, particles and aggregates, biological activity, and thermal stability and degradation studies.

Results: ABP 654 was found to be analytically similar to ustekinumab RP with respect to physicochemical and biological properties, including structure, function, purity, and potency.

Conclusions: Based on a comprehensive similarity assessment, ABP 654 was found to be similar to ustekinumab RP, notwithstanding minor physicochemical differences that are not expected to have a clinically meaningful effect on safety or efficacy.

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Conflict of interest statement

Greg Cantin, Qian Liu, Bhavana Shah, Scott Kuhns, Mats Wikström, Shawn Cao, and Jennifer Liu are employees and stockholders of Amgen Inc.

There is a plan to share data. This may include de-identified individual patient data for variables necessary to address the specific research question in an approved data-sharing request, and also related data dictionaries, study protocol, statistical analysis plan, informed consent form, and/or clinical study report. Data sharing requests relating to data in this manuscript will be considered after the publication date and (1) this product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or (2) clinical development discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for these data. Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). Complete details are available at https://wwwext.amgen.com/science/clinical-trials/clinical-data-transparency-practices/clinical-trial-data-sharing-request/. In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labeling. A committee of internal advisors reviews requests. If not approved, a Data Sharing Independent Review Panel may arbitrate and make the final decision. Requests that pose a potential conflict of interest or an actual or potential competitive risk may be declined at Amgen’s sole discretion and without further arbitration. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at http://www.amgen.com/datasharing.

Figures

Fig. 1
Fig. 1
Amino acid sequence by reduced peptide map assessment of ABP 654 and ustekinumab (US and EU). a 3-60 mins. b 60-120 mins. EU European Union, US United States
Fig. 2
Fig. 2
N-glycan map by HILIC assessment of ABP 654 and ustekinumab (US and EU). EU European Union, HILIC hydrophilic interaction liquid chromatography, US United States
Fig. 3
Fig. 3
Sialic acid linkage analysis of ABP 654 and ustekinumab (US and EU). Released N-glycans were analyzed by HILIC (glycan map) with and without treatment by linkage-specific neuraminidases. a HILIC profiles of ABP 654 for total glycans (black trace) and glycans after treatment with neuraminidase Au (specific for α2-3,6,8,9 linkages, blue trace) and neuraminidase Sp (specific for α2,3 linkage, pink trace). b HILIC profiles of ustekinumab (US) for total glycans (black trace) and glycans after treatment with neuraminidase Au (specific for α2-3,6,8,9 linkages, blue trace) and neuraminidase Sp (specific for α2,3 linkage, pink trace). c HILIC profiles of ustekinumab (EU) for total glycans (black trace) and glycans after treatment with neuraminidase Au (specific for α2-3,6,8,9 linkages, blue trace) and neuraminidase Sp (specific for α2,3 linkages, pink trace). EU European Union, HILIC hydrophilic interaction liquid chromatography, US United States
Fig. 4
Fig. 4
Size variant assessment of ABP 654 and ustekinumab (US and EU). a Side-by-side SE-UHPLC analysis. b Side-by-side rCE-SDS analysis. c Side-by-side nrCE-SDS analysis. EU European Union, HC heavy chain, HMW high molecular weight, LC liquid chromatography, LMW low molecular weight, MMW mid molecular weight, NGHC non-glycosylated heavy chain, US United States
Fig. 5
Fig. 5
Charge variant assessment by CEX-HPLC of ABP 654 and ustekinumab (US and EU). a Untreated samples. b Carboxypeptidase B-treated samples. c Carboxypeptidase B-treated plus PNGase F-treated samples.  CEX-HPLC cation exchange high-performance liquid chromatography, EU European Union, US United States
Fig. 6
Fig. 6
Primary mechanism of action assessment of ABP 654 and ustekinumab (US and EU). Individual lot results plotted along with the mean ± one SD.  EU European Union, IL interleukin, US United States
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