DEMONSTRATION OF FUNCTIONAL SIMILARITY OF PROPOSED BIOSIMILAR ABP 798 TO RITUXIMAB
Author(s): ,
Helen McBride
Affiliations:
Biosimilars Development,Amgen Inc.,Thousand Oaks,United States
,
Gwendolyn Maher
Affiliations:
Biosimilars Development,Amgen Inc.,Thousand Oaks,United States
,
Heather Sweet
Affiliations:
Biosimilars Development,Amgen British Columbia,Burnaby,Canada
,
Ian Foltz
Affiliations:
Biosimilars Development,Amgen British Columbia,Burnaby,Canada
,
Jude Canon
Affiliations:
Biosimilars Development,Amgen Inc.,Thousand Oaks,United States
Scott Kuhns
Affiliations:
Biosimilars Development,Amgen Inc.,Thousand Oaks,United States
EHA Learning Center. McBride H. May 18, 2017; 182563
Helen McBride
Helen McBride

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Abstract
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Abstract: PB1849

Type: Publication Only

Background

Proposed biosimilars undergo comprehensive structural and functional characterization before they can be studied in confirmatory clinical trials. ABP 798 is being developed as a biosimilar to rituximab. The originator is approved for treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, severe rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

Aims

ABP 798 was compared with rituximab sourced from the European Union (EU). Quality attributes assessed included binding properties (CD20, C1q, FcRn, and Fcγ receptors), antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and induction of apoptosis.

Methods

Binding of ABP 798 and rituximab to the CD20 antigen was characterized using a cell-based CD20 binding assay utilizing the human B-lymphoblastoid, WIL2-S, cell line. A direct binding ELISA was used to assess the binding of the Fc domain of ABP 798 to C1q. Binding of the Fc moiety of ABP 798 and rituximab to FcγRIa, FcγRIIa, FcγRIIb, and FcγRIIIa (158V) were evaluated in AlphaLISA® competitive binding assays. Binding to FcRn was evaluated by an AlphaScreen® competitive binding assay. ADCC activity was evaluated in a functional cell-based assay, with CD20-expressing WIL2-S cells used as target cells and NK92-M1 cells, stably transfected with human CD16 (FcγRIIIa [158V]), used as effector cells. CDC activity was evaluated in a functional cell-based assay using a CD20 expressing human B-lymphoblastoid WIL2-S cell line and baby rabbit complement. Induction of apoptosis was assessed by measuring activation of caspase 3/7 in SU-DHL-4 cells, a CD20-expressing human B cell lymphoma cell line.

Results
Relative binding (%) was comparable between ABP 798 and rituximab (Table).

Assay
ABP 798
Rituximab
CD20
91 – 105
82 – 105
C1q
85 – 100
85 – 89
FcRn
89 – 104
92 – 115
FcγRIa
94 – 98
87 – 95
FcγRIIa
96 – 102
96 – 106
FcγRIIb
96 – 108
93 – 109
FcγRIIIa (158V)
88 – 100
67 – 97
The dose response profiles and relative activity for ADCC and CDC were similar (mean ADCC relative activity: ABP 798, 88%; rituximab, 86%; mean CDC relative potency: ABP 798, 103%; rituximab, 104%). The dose response profile for induction of caspase 3/7 was comparable between ABP 798 and rituximab.

Conclusion

The results presented here suggest that ABP 798 is similar to rituximab sourced in the EU in terms of biological activity across the range of tested functions. These results provide a firm foundation for further clinical development of ABP 798.

Session topic: 24. Gene therapy, cellular immunotherapy and vaccination

Keyword(s): antibody, Rituximab, Immunotherapy

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