By: Jennifer Giordano-Coltart Ph.D.
On August 30, 2016, the Food and Drug Administration (FDA) approved the third U.S. biosimilar product – Sandoz Inc.’s (Sandoz) biosimilar of Amgen Inc.’s (Amgen) blockbuster Enbrel® (etanercept) – pursuant to the Biologics Price Competition and Innovation Act of 2009 (BPCIA).
Sandoz’s biosimilar, GP2015, will be marketed as Erelzi® (etanercept-szzs) and has been approved for all indications on the label of its reference product Enbrel®, including ankylosing spondylitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, and rheumatoid arthritis. The approval was expected following the unanimous vote for approval of the FDA’s Arthritis Advisory Committee in July.
In approving GP2015, the FDA concluded that the biosimilar was highly similar to U.S.-licensed Enbrel®, notwithstanding minor differences in clinically inactive components. FDA also found no clinically meaningful differences between GP2015 and the reference product in terms of the safety, purity, and potency of the product. Sandoz’s abbreviated Biologic License Application (aBLA) was supported by comparative pharmacokinetic studies in healthy volunteers and a confirmatory efficacy and safety similarity study in patients with chronic plaque psoriasis. Of note, the results of these studies were extrapolated to support approval of GP2015 for all other indications for which the reference product is approved. While approved as a biosimilar of Enbrel®, GP2015 was not approved as an interchangeable product
, though additional studies may support such a finding in the future.
Though it has received FDA-approval, Sandoz is currently barred from marketing Erelzi® in the United States due to ongoing litigation. In February 2016, Immunex Corp., Amgen Manufacturing, and Hoffman-La Roche filed suit against Sandoz asserting infringement of 5 patents allegedly covering etanercept under the BPCIA.
On August 11, 2016, based on a sealed stipulation agreed to by the parties, the court entered a consent preliminary injunction that provides that Sandoz will not “make, use, import, offer to sell, or sell” Erelzi®. Amgen has asserted that Enbrel® has U.S. patent protection until 2029 and is aiming to keep Erelzi® and other allegedly infringing products off the market until then. Trial is scheduled for April 17, 2018. In any case, Sandoz must give notice of commercialization to Amgen 180 days prior to launching Erelzi® into the U.S. market based on the recent Federal Circuit decision in Federal Circuit’s recent decision in Amgen v. Apotex
, No. 2016-1308 (Fed. Cir. July 5, 2016). The entry of biosimilars into the market is noticeably impacting prices and shifting market share worldwide. For example, once biosimilar competition entered the market for Remicade® in 2014/2015, sales of the drug fell 24%.
Similarly, four months after market entry of Zarxio®, Amgen’s market share for Neupogen® dropped to 76%.
Amgen is facing competition for Enbrel® in Europe as well. European approval of GP2015 is likely not far off as the European Medicines Agency (EMA) accepted Sandoz’s biosimilar application for the product last year. Also, in January 2016, EMA approved Biogen and Samsung Bioepis’s Benepali® etanercept biosimilar for marketing in Europe. The increased competition is likely to decrease Amgen’s market share and its $5.36 billion in annual revenues from Enbrel®. Download Copy  FDA approves Erelzi, a biosimilar to Enbrel
, FDA News Release (August 30, 2016), http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518639.htm
.  BLA 761042 GP2015, a proposed biosimilar to Enbrel (etanercept), Sandoz
, FDA Briefing Document, Arthritis Advisory Committee Meeting (July 13, 2016), http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwiB1Lby_PrOAhWPZiYKHaWGAeQQFggeMAA&url=http%3A%2F%2Fwww.fda.gov%2Fdownloads%2FAdvisoryCommittees%2FCommitteesMeetingMaterials%2FDrugs%2FArthritisAdvisoryCommittee%2FUCM510493.pdf&usg=AFQjCNE3xdGKrmHwY-yVidWByealiTt6Pg&bvm=bv.131783435,d.eWE
The case is Immunex Corp. et al. v. Sandoz Inc. et al.,
16-cv-01118-CCC-JBC (D.N.J.). The plaintiffs asserted claims of patent infringement under 35 U.S.C. § 271(e)(2)(C) based on Sandoz’s submission of the aBLA for GP2015 and declaratory judgment claims for patent infringement under 42 U.S.C. § 262(l
)(9) based on Sandoz’s refusal to participate in 42 U.S.C. § 262(l
)(4) or (5) of the BPCIA patent information exchange procedures (“patent dance”). 
Phil Taylor, Remicade safe from biosimilar competition this year, says J&J
, PMLive (April 20, 2016), http://www.pmlive.com/pharma_news/remicade_safe_from_biosimilar_competition_this_year,_says_j_and_j_1000477
Dan Stanton, First US biosimilar gradually eroding Amgen’s market share, Sandoz
, BioPharma-Reporter.com (January 29, 2016), http://www.biopharma-reporter.com/Markets-Regulations/Sandoz-s-biosimilar-Zarxio-gradually-eroding-Amgen-s-Neupogen-sales
See Amgen’s 2015 Revenues Increased 8 Percent to $21.7 Billion And Adjusted Earnings Per Share (EPS) Increased 19 Percent To $10.38
, Amgen News Release (January 28, 2016), http://www.amgen.com/media/news-releases/2016/01/amgens-2015-revenues-increased-8-percent-to-217-billion-and-adjusted-earnings-per-share-eps-increased-19-percent-to-1038/.