277clinical use [ 66 ]. Because of the greater costs and time for research and develop-
ment for a given biosimilar, the most ideal factors for potential biosimilars are bio-
logic agents with patents near expiration, with the potential for extrapolation across
disease states, and with the possibility of interchangeability [ 62 ]. However, the
complexities of manufacturing the biosimilars according to the FDA-mandated
standards, the costs of clinical trials to demonstrate the bioequivalence, the need for
post-marketing surveillance or pharmacovigilance to report safety and immunoge-
nicity outcomes, and the uncertainty regarding interchangeability or automatic sub-
stitution with branded agents are potential barriers to biosimilar development and
encourage corporate partnering or acquisitions, e.g., Pfizer acquired Hospira which
held the American rights to CT-P13. Since the release of CT-P13 to the European
Market in 2013, the average discounts in cost compared to Remicade® are an esti-
mated 25% with a range of 10–30% savings [ 67 ].
Market Financials Influencing Anti-TNF Biosimilars
in the USA
The potential cost savings with the use of biosimilar anti-TNFs are enormous con-
sidering the 2014 global sales of Humira (Abbvie pharmaceuticals) of $13.0 billion
and $10.1 billion for Remicade [ 68 ]. However, in the EU market, penetration of
CT-P13 varies widely, based on pricing discounts, status of tender nations, and
authority of central national payers. In the USA, Pfizer began shipping Inflectra in
November of 2016, and estimates of market uptake of CT-P13 range between 15
and 30% over the first 3 years of market availability. Merck, which markets in
Europe, sustained a loss of sales of Remicade from $2.3 billion in 2014 to $1.8 bil-
lion in 2015 after the introduction of the Remicade biosimilar [ 69 ]. Additionally in
September 2016,the FDAannounced approval of ABP 501 after positive results in
RA and psoriasisand can further serve to discount pricing of anti-TNF agents [ 70 ].
In March 2015, Janssen filed for patent infringement by Celltrion on six patents
related to Abbvie which has stated that although the composition of matter patent
for Humira expires in December 2016, an additional total of 70 patents regarding
formulation, manufacturing, and methods of use do not expire until 2022 and
announced their strategy of attempting to block the introduction of ABP 501 based
on claims of patent infringement.
Conclusions
The approvals of the first anti-TNF biosimilars, CT-P13 and ABP 501 for inflix-
imab and adalimumab, respectively, throughout the world have ushered in a new
era of prescribing possibilities for anti-TNF drugs. This approval for IBD was
extrapolated to IBD from a single RCT in RA and AS, respectively, for CT-P13,and
15 Biosimilars in Inflammatory Bowel Disease 2017: State of the Science