You are here

Clinical trial development for biosimilars

Seminars in Arthritis and Rheumatism, Volume 44, Issue 6, June 2015, Pages S2 - S8

Abstract

Objectives

Discuss issues regarding clinical trial design for the development of biosimilars in the European Union and the United States, with special focus on monoclonal antibodies used in the treatment of inflammatory diseases.

Methods

A search of the Internet as well as PubMed was conducted through June 2014 for information related to the clinical development of biosimilars using the keywords biosimilar, rheumatoid arthritis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and ankylosing spondylitis. The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) websites were searched for biosimilar guidelines.

Results

The EMA began issuing draft guidelines for the development of biosimilars almost a decade ago and has approved numerous biosimilars. The US FDA has issued draft guidances providing stepwise considerations for the nonclinical and clinical development of biosimilars but has yet to approve a biosimilar under this pathway.

Conclusions

Clinical trials aim to resolve uncertainties that may remain following nonclinical development regarding the similarity of the proposed biosimilar with the reference product. Pharmacokinetic and pharmacodynamic studies form the backbone of early clinical development and serve to inform phase 3 clinical development. Factors to be considered in clinical development include study population, design, end points, sample size, duration, and analytical methods.

Keywords: Biosimilar, biologic, reference product, chronic inflammatory diseases, clinical studies, comparability, immunogenicity, extrapolation, pharmacokinetics, pharmacodynamics, regulatory guidances, study design, safety.

Footnotes

a Department of Internal Medicine II, Rheumatology, Clinical Immunology, Osteology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany

b Rheumatology Research Center, Rheumatology, Clinical Immunology, Osteology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany

c Clinical and Translational Science Institute, NYU School of Medicine, New York, New York

Corresponding author at: Rheumatology Research Center, Rheumatology, Clinical Immunology, Osteology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany.

This supplement was funded by Pfizer Inc. Rieke Alten, MD, Bruce Cronstein, MD, Walter Reinisch, MD, and Josef Smolen, MD, were paid consultants to Pfizer Inc for the research and/or authorship of this supplement. Medical writing and editorial support to prepare this supplement was provided by John Pryor of QD Healthcare Group and funded by Pfizer Inc. Rieke Alten has no additional conflicts of interest to disclose. Bruce Cronstein has the following additional conflicts of interest to disclose: consultant: Bristol-Myers Squibb, Eli Lilly and Company, Regeneron; research grants: AstraZeneca, UK; Celgene, USA; Gilead; Takeda Pharmaceutical Company Limited. Walter Reinisch has the following additional conflicts of interest to disclose: consultant: AbbVie, Amgen, Celltrion, Janssen, MSD.