Comparative Clinical Efficacy and Safety of the Proposed Biosimilar ABP 710 With Infliximab Reference Product in Patients With Rheumatoid Arthritis

Mark C. Genovese; Juan Sanchez-Burson; MyungShin Oh; Eva Balazs; Jeffrey Neal; Andrea Everding; Tomas Hala; Rafal Wojciechowski; Gary Fanjiang; Stanley Cohen

Disclosures

Arthritis Res Ther. 2020;22(60) 

In This Article

Background

ABP 710 is being developed as a biosimilar to infliximab reference product (RP) (Remicade®). Remicade® is approved in the USA and EU for the treatment of adult and pediatric Crohn's disease, adult and pediatric ulcerative colitis, rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.[1,2] Biologics have revolutionized the treatment of autoimmune disorders; however, they are expensive options, leading to limited access to treatment. Recently, in an effort to provide alternative treatment options, regulatory agencies have established guidelines to provide an abbreviated development and approval pathway for biosimilars. Guidance from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) outline a stepwise, totality-of-evidence-based approach to the development of a proposed biosimilar, with evaluation of any residual uncertainty about biosimilarity at each step.[3–5] The evaluation of biosimilarity begins with demonstration of analytical (structural, functional, and physiochemical) similarity, which forms the foundation of biosimilarity. This is then followed by comparative preclinical and clinical pharmacology evaluations, including human pharmacokinetics (PK) and pharmacodynamics, if relevant, and finally at least one comparative clinical study to evaluate the similarity of efficacy, safety, and immunogenicity in a representative indication using a sensitive patient population and endpoints to complete the totality of evidence.

ABP 710 and infliximab RP are both chimeric immunoglobulin G monoclonal antibodies produced by recombinant DNA technology, with the same primary amino acid sequence, product strength, dosage form, and formulation upon reconstitution. ABP 710 is similar in secondary and tertiary structure as well as overall conformational stability.[6] The similarity of ABP 710 with infliximab RP for in vitro binding to tumor necrosis factor alpha, FcRn, and FcγRIIIa and in vitro effector function activity of antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity has been demonstrated through multiple sensitive biological characterization assays (Saleem R, Cantin G, Wikstroem M, Bolton G, Kuhns S, McBride HJ, Liu J: ABP 710: analytical and functional similarity with infliximab reference product, submitted). In a clinical PK study in healthy adult patients, similarity of ABP 710 with infliximab RP was demonstrated through comparisons of area under the serum concentration-time curve from time 0 extrapolated to infinity.[7] This comparative clinical study was designed to demonstrate the similarity of ABP 710 with infliximab RP in efficacy, safety, and immunogenicity in patients with moderate to severe RA.

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