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Abstract Number: 1503

Demonstration of Functional Similarity Comparing Adalimumab to Biosimilar Candidate ABP 501

Teresa Born1, Jyoti Velayudhan2, Yuh-fung Chen3, Heather Thomas4, Christina Pastula2, Gwen Maher3 and Ryan Brown4, 1Biosimilars Process Development, Amgen, Seattle, WA, 2Functional Biocharacterization, Amgen, Seattle, WA, 3Functional Biocharacterization, Amgen, Thousand Oaks, CA, 4Inflammation Research, Amgen, Seattle, WA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Adalimumab and biosimilars

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Session Information

Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Novel therapies, Biosimilars, Strategies and Mechanisms in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: ABP 501 is being developed as a biosimilar to adalimumab, a recombinant monoclonal antibody that binds tumor necrosis factor alpha (TNF) thus inhibiting engagement of TNF receptors and initiation of consequent proinflammatory signaling.  Although adalimumab and intended biosimilars share the same amino acid sequence, differences will likely exist in product quality attributes due to differences in proprietary expression systems, bioprocess and purification.  Equivalence of product quality attributes, especially demonstration of comprehensive functional equivalence, is of primary importance during stepwise development of a biosimilar in order to provide confidence for similar clinical safety and efficacy in patients, including extrapolation to all indications of use.

Methods: The similarity assessment of biological activity included testing binding of ABP 501 and adalimumab to soluble TNF by surface plasmon resonance and to cell-surface expressed TNF (mbTNF) in a competitive imaging cytometry-based assay. The similarity assessment for F(ab)-mediated activity included blocking TNF-induced caspase activation, IL-8 secretion and cytotoxicity.   Inhibition of TNF activity in healthy volunteer blood samples stimulated ex vivo was also compared.  To assess Fc-mediated functions, binding to the neonatal Fc receptor (FcRn) was measured in a competitive cell-based assay and to FcγRIIIa (158V) by AlphaLISATM.  To confirm similarity in Fc-mediated functions, antibody-dependent cell-mediated cytotoxicity (ADCC) was assessed using cells expressing mbTNF and NK92-M1 cells expressing FcγRIIIa (158V).  Complement-dependent cytotoxicity (CDC) was also tested, using complement and cells expressing mbTNF.  Data from up to three lots of each antibody were assessed in the described assays as part of the initial similarity assessment.

Results: Equilibrium binding affinity to TNF was similar between ABP 501 (48-52 pM) and adalimumab (48-53 pM). Binding to mbTNF was also similar between ABP 501 (100-106% relative binding) and adalimumab (100-111%).  Relative potency in the caspase activation assay was similar between ABP 501 (103-107%) and adalimumab (100-110%).  Dose response profiles and resulting EC50 values in the IL-8 secretion (192-294 pM for ABP 501 and 156-253 pM for adalimumab), cytotoxicity (390-457 pM for ABP 501 and 391-544 pM for adalimumab) and whole blood assays, measuring both MCP-1 and MIP-1 beta production, were also similar between ABP 501 and adalimumab.

Binding to FcRn was similar between ABP 501 (86-94%) and adalimumab (92-114%) as was binding to FcγRIIIa (158V) comparing ABP 501 (103-113%) to adalimumab (92-94%). The dose response profile for ADCC (101% relative cytotoxicity for ABP 501 and 107% for adalimumab) and CDC (97% relative cytotoxicity for ABP 501 and 93% for adalimumab) were also similar.

Conclusion: Results from an initial similarity assessment demonstrate that ABP 501 is functionally highly similar to adalimumab in multiple sensitive preclinical pharmacologic assays.


Disclosure:

T. Born,

Amgen,

3,

Amgen,

1;

J. Velayudhan,

Amgen,

3,

Amgen,

1;

Y. F. Chen,

Amgen,

1,

Amgen,

3;

H. Thomas,

Amgen,

1,

Amgen,

3;

C. Pastula,

Amgen,

1,

Amgen,

3;

G. Maher,

Amgen,

1,

Amgen,

3;

R. Brown,

Amgen,

1,

Amgen,

3.

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