262
RCT Randomized controlled trial
TNF Tumor necrosis factor
UC Ulcerative colitis
WHO World Health Organization
Introduction
The year 2016 witnessed the FDA approval of the first biosimilar agents for the
antitumor necrosis factors (anti-TNF): infliximab (IFX, Janssen) and adalimumab
(ADA, Abbvie). Based on a single trial in rheumatoid arthritis (RA) and ankylosing
spondylitis, respectively, the biosimilar for IFX, CT-P13 (Celltrion Inc.) was
approved, andABP 501 was approved as the first biosimilar for ADA based on a
single trial in RA and psoriasis, respectively. Despite patent challenges,Pfizer began
sales ofInflectra in December 2016, and despite patent challenges, sales ofABP-501
will soon follow [ 1 ]. Considering that the cost of anti-TNF agents has become the
largest expenditure in the care of IBD patients, the savings in drug costs will be a
major driver in the adoption of anti-TNF biosimilars.
An abbreviated pathway for biosimilar drug developmentwas established as part
of the Patient Protection and Affordable Care Act (ACA, also referred to Obamacare),
which was signed into law in March 2010. Within the ACA, the Biologic Price and
Competition Act (BPCI) was created to facilitate development of biosimilar drugs,
aiming forthe introduction ofless expensive drugs with the goal of enhancing greater
patient access to costly biologic agents [ 2 ]. While the election of Donald Trump has
led to efforts to repeal segments of the ACA, there has, to date, not been a public
discussion of plans to address the BPCI. The BPCI created an abbreviated new drug
application (aNDA), known as the 351(k) pathway for a proposed biosimilar drug.
This newly established pathway allows for anew drug application based on a lesser
amount of clinical data and instead requires a greater analysis to establish physio-
chemical, pharmacokinetic, and pharmacodynamic similarity to the originator com-
pound [ 3 ].
The FDA definition ofa biosimilar drug is a “biological product that is highly
similar to the reference product not withstanding minor differences in clinically
inactive components... [with] no clinically meaningful differences between the bio-
logical product and the reference product in terms of the safety, purity, and potency
of the product” [ 2 ]. It is important to recognize that the chemical structure of a
biosimilar drug, in contrast to generic drugs, is not an identical copy with the same
chemical form of the original reference drug. Biosimilars are larger and more com-
plex biological compounds with the potential for immunogenicity similar to origi-
nator biologic agents, and may be prone to posttranslational modification, which
may potentially influence clinical outcomes and immunogenicity.
The focus of this chapter will be primarily on the biosimilar CT-P13 for inflix-
imab since the randomized controlled trials for this compound have already been
C.Y. Ha and A. Kornbluth