Etanercept

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. TNF is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF.[12]

Etanercept is a fusion protein produced by recombinant DNA. It fuses the TNF receptor to the constant end of the IgG1 antibody. First, the developers isolated the DNA sequence that codes the human gene for soluble TNF receptor 2, which is a receptor that binds to tumor necrosis factor. Second, they isolated the DNA sequence that codes the human gene for the Fc end of immunoglobulin G1 (IgG1). Third, they linked the DNA for TNF receptor 2 to the DNA for IgG1 Fc. Finally, they expressed the linked DNA to produce a protein that links the protein for TNF receptor 2 to the protein for IgG1 Fc.[13]

Society and culture

Economics

The US retail price of etanercept has risen over time. In 2008, the cost of etanercept was $1,500 per month or $18,000 per year.[44] By 2011, the cost had exceeded $20,000 per year.[45][46] In 2013, a survey by the International Federation of Health Plans (IFHP) found that the average US cost for etanercept was $2,225 per month, or $26,700 per year.[47] The IFHP report also found wide variation in prices charged to various US health plans, between $1,946 per month at the 25th percentile and $4,006 per month at the 95th percentile.[47]

Etanercept is more expensive in the US than in other countries.[47] As of 2013, average monthly costs in surveyed nations ranged from $1,017 in Switzerland to $1,646 in Canada, compared to an average monthly cost of $2,225 per month in the US.[47]

Amgen sells etanercept within the US and Canada, while Pfizer, Inc. sells the drug outside of the US and Canada.[45] Sales within the US and Canada were $3.5 billion in 2010.[45] Sales of etanercept outside the US and Canada were $3.3 billion in 2010.[48]

In late March 2025, Amgen lost a lawsuit against Colorado over a prescription drug affordability board.[49]

Patents

The patent on etanercept was set to expire in October 2012,[50] but, in the United States, a second patent, granting exclusivity for another 16 years, has been granted.[51]

Before the extension it seemed unlikely that a generic would have been available. As a biologic, etanercept is subject to different laws from those applicable to chemical formulations. Many countries do not permit the manufacture of generic biologics. However, the European Union and the United States (Biologics Price Competition and Innovation Act of 2009) do have in place a system to approve generic biologics (biosimilars) which "requires mandatory clinical testing and periodic review".[52]

In April 2013, the Indian pharma major Cipla made an announcement about launching the first biosimilar of Etanercept in India under the brand name Etacept for the treatment of rheumatic disorders.[53]

Biosimilars

In January 2016, Benepali was approved for use in the European Union.[54]

In February 2017, Lifmior was approved for use in the European Union.[55] It was withdrawn from the market in February 2020.[56]

In June 2017, Erelzi was approved for use in the European Union.[57]

In March 2019, YLB113 (Etanercept biosimilar by YL Biologics) was approved in Japan.[58]

In April 2019, Eticovo received FDA approval.[59]

width	153
tradename	Enbrel
medlineplus	a602013
dailymedid	Etanercept
pregnancy au	D
pregnancy au comment	‡R1R‡
routes of administration	Subcutaneous
atc prefix	L04
atc suffix	AB01
biosimilars	etanercept-szzs, etanercept-ykro, Benepali, Brenzys,‡R2R‡ Erelzi,‡R3R‡‡R4R‡ Etacept, Etera, Eticovo, Lifmior, Nepexto, Rymti
legal au	S4
legal ca	Rx-only
legal ca comment	/ Schedule D‡R5R‡
legal uk	POM
legal uk comment	‡R6R‡‡R7R‡‡R8R‡
legal us	Rx-only
legal us comment	‡R9R‡
legal eu	Rx-only
legal eu comment	‡R10R‡‡R11R‡
bioavailability	58–76% (SC)
elimination half-life	70–132 hours
cas number	185243-69-0
pubchemsubstance	7847807
drugbank	DB00005
chemspiderid	None
unii	OP401G7OJC
kegg	D00742
chembl	1201572
c	2224
h	3475
n	621
o	698
s	36

Medical uses

Unrecognized uses

Adverse effects

Mechanism of action

Structure

History

Society and culture

Economics

Patents

Biosimilars

References