Background/Purpose:

ABP 710 is being developed as a biosimilar to infliximab, a recombinant chimeric monoclonal antibody that binds tumor necrosis factor alpha (TNFa) and inhibits the TNF receptor-mediated downstream pro-inflammatory signaling cascade. Although ABP 710 and infliximab reference product have the same primary amino acid sequence differences in production cell line and the manufacturing process can impact product quality attributes that may be critical for in vivo efficacy, pharmacokinetics and immunogenicity. To demonstrate that ABP 710 is similar to the reference product, we performed a comprehensive comparative biological characterization of ABP 710 with infliximab reference product.

Methods:

The functional similarity assessment of ABP 710 and infliximab reference product included: 1) binding to soluble (s) TNFa by ELISA, 2) binding to membrane-bound (mb) TNFa by a competitive imaging cytometry-based assay, 3) inhibition of sTNFa-induced apoptosis in the U937 cell line, and 4) reverse signaling via induction of apoptosis in mbTNFa-expressing Jurkat cells. To confirm similarity of Fc-mediated functions, antibody-dependent cell-mediated cytotoxicity (ADCC) was assessed using cells expressing mbTNFa as target cells and NK92-M1 cells expressing FcγRIIIa (158V) as effector cells. In addition, complement-dependent cytotoxicity (CDC) was assessed using rabbit complement and cells expressing mbTNFa. Data from at least three lots of ABP 710 and infliximab reference product sourced from the US (IFX-US) and infliximab reference product sourced from the EU (IFX-EU) were assessed as described.

Results:

Relative binding of ABP 710 to sTNFa (ABP 710 =93-105%; IFX-US =88-101%; IFX-EU =93-104%) and mbTNFa (ABP 710 =101-109%; IFX-US =99-106%; IFX-EU =105-113%) were similar between ABP 710 and infliximab reference product. Relative inhibition of apoptosis in U937 cells (ABP 710 =87-112%; IFX-US =78-115%; IFX-EU =89-114%), and to induce apoptosis in Jurkat cells expressing mbTNFa (ABP 710 =99-105%; IFX-US =90-114%; IFX-EU =96-107%) were also similar between ABP 710 and infliximab reference product. Fc-mediated functions, ADCC (ABP 710=102-133%; IFX-US =91-169%; IFX-EU =100-166%) and CDC (ABP 710 =96-110%; IFX-US =93-136%; IFX-EU =98-135%) were similar as well between ABP 710 and infliximab reference product.

Conclusion:

As one aspect of the “totality of evidence” approach to support similarity, results from this assessment demonstrate that ABP 710 is functionally similar to infliximab reference product in multiple sensitive biological characterization assays.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/abp-710-matching-critical-biological-functions-with-infliximab/