The Science Behind Biosimilars

An important challenge currently facing rheumatologists and rheumatology health professionals is to gain an understanding of the landscape surrounding biosimilar agents, including the scientific, clinical, economic, and prescribing issues related to their use. The US Food and Drug Administration (FDA) defines a biosimilar as a biologic product that is “highly similar to” an approved biologic product (the “reference,” “originator,” or “biooriginator” product) and that has “no clinically meaningful differences” in safety or effectiveness as compared to the reference product (1). The number of biosimilars in development has burgeoned since the Biologics Price Competition and Innovation (BPCI) Act of 2009 was passed by the US Congress with the intent of reducing costs and thereby increasing patients’ access to biologics. Another factor driving development of biosimilars is that the exclusivity period, as defined by the FDA, is approaching completion for several biologics. Nomenclature for biosimilars in the US uses the common nonproprietary name followed by a 4-letter suffix, so that each drug, both reference product and biosimilar, will have a unique nonproprietary name. Proprietary names, in contrast, are generated by the manufacturer and may vary from country to country for the same drug. As of December 2017, the FDA had approved 9 biosimilars, 6 of which are tumor necrosis factor (TNF) inhibitors, for rheumatologic and other inflammatory diseases: infliximab-dyyb (Inflectra), infliximab-abda (Renflexis), and infliximab-qbtx (Ixifi) (biosimilars of infliximab [Remicade]), etanercept-szzs (Erelzi) (biosimilar of etanercept [Enbrel]), and adalimumab-adbm (Cyltezo) and adalimumab-atto (Amjevita) (biosimilars of adalimumab [Humira]) (2–5). Many additional biosimilars of reference products with indications for both rheumatologic and nonrheumatologic diseases are under development. An updated list of approved biologics and biosimilars is available online in the “Purple Book” through the FDA Center for Drug Evaluation and Research (6). Biosimilars should not be confused with generic medications, despite the fact that for both, pathways for regulatory approval are abbreviated as compared to the pathways for approval of new drugs (Figure 1). The chemical structure of a generic small-molecule drug must be identical to that of its reference product. Thus, once chemical identity has been demonstrated, approval of a S. Louis Bridges Jr., MD, PhD: University of Alabama at Birmingham; Douglas W. White, MD, PhD: Gundersen Health System, La Crosse, Wisconsin; Angus B. Worthing, MD: Georgetown University Medical Center and Arthritis & Rheumatism Associates, Washington, DC; Ellen M. Gravallese, MD, Jonathan Kay, MD: University of Massachusetts Medical School, Worcester; James R. O’Dell, MD: University of Nebraska Medical Center, Omaha; Kamala Nola, PharmD, MS: Lipscomb University College of Pharmacy and Health Sciences, Nashville, Tennessee; Stanley B. Cohen, MD: Metroplex Clinical Research Center, Dallas, Texas. Dr. Gravallese has received consulting fees from Eli Lilly and Company, Sanofi, and Janssen (less than $10,000 each) and grant support from AbbVie, Eli Lilly and Company, and Pfizer. Dr. O’Dell has received consulting fees from Medac and Coherus (less than $10,000 each). Dr. Kay has received consulting fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Biotech, Merck Sharp & Dohme, Pfizer, Roche Laboratories, Samsung Bioepis, and UCB (less than $10,000 each) and from Amgen and Sandoz (more than $10,000 each). Dr. Cohen has received consulting fees from Amgen, Boehringer Ingelheim, Merck, Pfizer, and Sandoz (less than $10,000 each). Address correspondence to S. Louis Bridges Jr., MD, PhD, University of Alabama at Birmingham, Clinical Immunology and Rheumatology, 1720 2nd Avenue South, 178 SHEL, Birmingham, AL 35223. E-mail: sbridges@uabmc.edu. Submitted for publication August 22, 2017; accepted in revised form November 16, 2017.