Comparative functional and pharmacological characterization of Sandoz proposed biosimilar adalimumab (GP2017): rationale for extrapolation across indications

ABSTRACT

Background: Biosimilars are approved biologics that match reference medicine in quality, safety, and efficacy. The development of Sandoz proposed biosimilar adalimumab (SPBA; GP2017) involved a target-directed, iterative state-of-the-art quality-by-design development program. Here, we describe the functional and pharmacological characterization of SPBA and its proposed mechanism of action in immune-mediated inflammatory diseases.

Methods: Sensitive in vitro binding and functional characterization studies, and nonclinical evaluations (pharmacokinetics, pharmacodynamics, and safety/toxicology) were performed as part of a stepwise approach to confirm the biosimilarity of SPBA with reference adalimumab.

Results: Matching values were reported for SPBA and reference adalimumab in binding assays involving tumor necrosis factor (TNF)-α, complement 1q and human immune effector cell Fcγ receptor subtypes in cell-based bioassays for Fc receptor function (complement- and antibody-dependent cytotoxicity), and in apoptosis inhibition. Furthermore, SPBA and reference adalimumab were equivalent in terms of membrane TNF binding and induction of reverse signaling. Pharmacokinetics of SPBA and reference adalimumab were comparable in rabbits, and the two biologics were equally effective in a human TNF transgenic mouse model of polyarthritis.

Conclusion: SPBA matches reference adalimumab with regards to target binding, functional, pharmacokinetic, and pharmacodynamic properties at the nonclinical level supporting its approval in all indications of the reference adalimumab.

KEYWORDS:

• Adalimumab
• biosimilar
• extrapolation
• GP2017
• inflammatory bowel disease
• tumor necrosis factor-alpha

Author contributions

All authors were involved in the conception and design of the study and the analysis and interpretation of the data. All authors reviewed and revised the manuscript and provided their approval of the final version of the manuscript. All authors agree to be accountable for all aspects of the work.

Acknowledgments

The authors thank Dr. Jacki Kornbluth of St. Louis University for kindly providing the natural killer cell line (NK3.3). The authors acknowledge the role of BioMedCode relating to studies involving the human Tg197 TNF transgenic mouse model of polyarthritis in identifying sensitive study designs to optimally address efficacy comparability in this well-establish and characterized disease model.

Declaration of interest

Ulrich Kronthaler, Otmar Hainzl, Andreas Seidl and Antonio da Silva are paid employees of Sandoz Biopharmaceuticals/Hexal AG, Holzkirchen, Germany. Cornelius Fritsch is a paid employee of Novartis Pharma AG, Basel, Switzerland. Editorial assistance was provided by Dr. Steve Clissold and Dr. Peter Weber of ContentEdNet, Germany. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by Sandoz Biopharmaceuticals/Hexal AG.