Biosimilars in Inflammatory Bowel Disease 2017: State of the Science, State of the Art, and State of the Finances

Abstract

Biosimilars are defined as highly similar but not chemically identical to the original (also known as the reference) biologic drug. In order to obtain regulatory approval, an anti-TNF biosimilar must prove that there is “highly similar” structural, physiochemical, pharmacokinetic (PK), pharmacodynamic (PD) mechanism of anti-TNF binding and neutralization and no “clinically meaningful differences between the biological and the reference product in terms of safety, purity, and potency.” In randomized controlled trials (RCTs) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), comparing reference infliximab and CT-P13 (Celltrion, Inc.), the first infliximab biosimilar, comparable clinical results in terms of efficacy, safety, and immunogenicity were found.Similarly, an adalimumab biosimilar ABP 501 (Amgen, Inc.) was approved based on extrapolation from a single RCT in RA and psoriasis, respectively.Indication extrapolation for a biosimilar can be granted by regulatory agencies for diseases in which it has not been studied, if the disease pathophysiology and mechanism of actions of the drug are considered comparable between diseases. Based on these factors, the FDA approved CT-P13 (Inflectra, Pfizer Inc.)and ABP 501 as biosimilars for infliximab and adalimumab, respectively, in 2016 for all diseases for which infliximaband adalimumab had previously been approved, including adult and pediatric moderate to severe UC and pediatric and adult moderate to severe and fistulizing CD. This was despite the absence of any randomized controlled trials (RCTs) studying these anti-TNF biosimilars in any inflammatory bowel disease (IBD).In January 2017, the FDA issued theirguidance document regarding the critical issue of interchangeability,whereby an approved biosimilar can be substituted for a prescribed reference drug without the approval or even the knowledge of the prescribing physician or patient.