European Roll Out For Samsung Bioepis's Etanercept Biosimilar

After gaining two regulatory approvals for its biosimilars at home last year, South Korea's Samsung Bioepis has now received its first overseas clearance for an etanercept biosimilar, in Europe. Benepali, which will be Europe's first biosimilar version of the fusion protein, is set to enter 31 European markets.

SEOUL - Samsung Bioepis Co. Ltd. has received marketing approval from the European Commission for its biosimilar version of Amgen Inc.'s Enbrel (etanercept), making it likely to be the first etanercept biosimilar to debut in Europe.

The latest approval paves the way for the South Korean biopharma's biosimilar to be gradually rolled out as Benepali (previously known as SB4) in 31 European countries - 28 EU member states as well as the European Economic Area (EEA) member states of Norway, Iceland and Liechtenstein - for the treatment of rheumatoid arthritis, psoriatic arthritis (PsA), axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis) and plaque psoriasis.

"We expect to roll out the product from the first quarter, or in the first half, of this year in Europe. But situations are different by country, so the launching date will be different for each country," said a spokesperson at Samsung Bioepis.

Aside from Europe and South Korea, the company is also undergoing a regulatory approval process for the etanercept biosimilar in Canada, she added.

In accordance with a commercialization agreement signed in 2013 between Samsung Bioepis and Biogen Inc., Biogen will lead the commercialization and distribution of Benepali in the EU and EEA member states. Samsung Bioepis, established in 2012, is a joint venture between Samsung Group affiliate Samsung BioLogics and Biogen.

The EC approval follows a positive opinion on Benepali by the European Medicines Agency's Committee for Medicinal Products for Human Use, which was announced on Nov. 20, 2015.

Benepali, which is called Brenzys in South Korea, began to be prescribed in South Korea in December following the greenlight from the Ministry of Food and Drug Safety in September (Also see "Korean Green Light For Samsung Bioepis’s Biosimilar Etanercept" - Scrip, 7 Sep, 2015.).

In December, the company also gained a second biosimilar regulatory approval in South Korea, for the infliximab biosimilar Renflexis (Also see "Korea Approves Second Biosimilar Infliximab" - Scrip, 9 Dec, 2015.).

"Benepali gives physicians another high-quality medicine to treat autoimmune patients across Europe," said Paul Emery, Arthritis Research UK professor of rheumatology at Leeds University. "Benepali's affordability may allow more patients from a wider demographic to receive proper treatment."

Multiple Phase III Biosimilars

“In addition to Benepali, we continue to advance one of the industry’s broadest biosimilar pipelines with multiple biosimilar candidates in Phase III clinical trials. Over the coming months, a number of them will be filed for regulatory approval in markets across the world," said Christopher Hansung Ko, president & CEO of Samsung Bioepis.

Enbrel is a dimeric fusion protein consisting of the extracellular ligand-binding portion of TNF receptor linked to the Fc portion of human immunoglobulin G1. Enbrel binds specifically to circulating TNF and blocks its interaction with cell surface TNF receptors, thereby retarding inflammation in autoimmune diseases. It is produced by recombinant DNA technology in a Chinese hamster ovary mammalian cell expression system.

In 1998, Enbrel was the first TNF inhibitor to receive approval and then launch for rheumatoid arthritis in the US. Since then, the drug's indications have expanded to include polyarticular juvenile idiopathic arthritis, PsA, plaque psoriasis, and ankylosing spondylitis. Enbrel was approved for the treatment of PsA in the US and EU in January 2002 and December 2002, respectively.

In August 2003, the US FDA granted approval for a label extension for Enbrel to include the progression of structural damage in patients with PsA, and in May 2005, the FDA approved a further expansion to Enbrel's label to include the improvement of physical function in PsA patients, according to Datamonitor Healthcare.

Global sales of Enbrel totaled $8.5bn in 2014. Its primary patent expiry dates are January 2015 for EU, April 2029 for the US and January 2017 for Japan.

Datamonitor forecasts Enbrel to lose up to 55% of its patient share to biosimilar etanercept across all markets. This is even though the initial uptake of biosimilars may be slow as rheumatologists prescribe them cautiously; initial prescribing is expected to be weighted towards new patients, Datamonitor analysts say.

In a 52-week Phase III clinical study, Benepali demonstrated comparable safety and equivalent efficacy to Enbrel, as evidenced by a ACR20 response rate of 80.8% in the Benepali arm versus 81.5% in the Enbrel arm. The study randomized 596 patients with moderate to severe rheumatoid arthritis despite methotrexate therapy across 70 sites in 10 countries (Also see "New Samsung Biosimilar Results Bode Well For Portfolio" - Scrip, 16 Nov, 2015.).

Samsung Bioepis is solely responsible for the development and manufacture of all immunology and oncology biosimilars in its pipeline, as well as global clinical trials and regulatory registration in all markets worldwide for these biosimilars.

Following approval, Samsung Bioepis biosimilars are marketed and distributed by its commercialization partners, Biogen and Merck & Co. Inc., with whom Samsung Bioepis has commercialization agreements that cover the first six biosimilars in the company's pipeline.

Samsung Bioepis’s biosimilar candidates and regions covered by its partners are as follows:

Partner	Biosimilar	Reference Drug	Regions
Biogen	SB4	Enbrel (etanercept)	EU, Switzerland, Japan
	SB2	Remicade (infliximab)	EU, Switzerland, Russia, Turkey
	SB5	Humira (adalimumab)	EU, Switzerland, Russia, Turkey
Merck	SB4	Enbrel (etanercept)	Worldwide excluding US, EU, Switzerland, Japan
	SB2	Remicade (infliximab)	Worldwide including US, but excluding EU, Switzerland, Russia, Turkey
	SB5	Humira (adalimumab)	Worldwide including US, but excluding EU, Switzerland, Russia, Turkey
	SB3	Herceptin (trastuzumab)	Worldwide
	SB9	Lantus (insulin glargine)	Worldwide