After Four Years, $7 Billion Blockbuster Etanercept Gains Another Domestic Contender as Qilu Pharma Submits上市 Application

On May 21, the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) announced that Qilu Pharmaceutical had submitted its etanercept biosimilar for marketing approval, with acceptance number CXSS1900024. This development signals the entry of another strong competitor into China’s etanercept market.

Etanercept is the first TNF antagonist approved for the treatment of rheumatoid arthritis (RA). Co-developed by Amgen and Pfizer, it received approval from the U.S. FDA on November 2, 1998, from the European EMA on February 3, 2000, and from the Japanese PMDA on January 19, 2005. Etanercept was introduced to the Chinese market at a later date, receiving approval on February 26, 2010, under the brand name “Enbrel.”

Domestic development of etanercept biosimilars began relatively early in China. Yisaipu, an etanercept biosimilar developed by 3SBio (a subsidiary of Sinopharm), was approved for marketing in 2005, predating the domestic launch of the originator etanercept. Additionally, Shanghai Saijin’s Qiangke and Hisun Pharmaceutical’s Anbainuo were approved for marketing in 2012 and 2015, respectively.

Table 1 Etanercept Drugs Marketed in China

Etanercept: One of the Leading Drivers Among TNF-α Inhibitors

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease, with 70% of RA patients presenting with moderate to severe disease.

Since tumor necrosis factor-alpha (TNF-α) was identified as the primary pro-inflammatory cytokine in autoimmune arthritis in the 1970s, more than two decades of research have ensued. In 1998, researchers successfully developed TNF-α inhibitors, a class of biologic agents for immunosuppressive therapy, and applied them to the clinical treatment of rheumatoid arthritis, demonstrating favorable efficacy.

Nature's Predicted Market Share of RA Drugs in 2019

According to Nature’s forecast, the global market size for rheumatoid arthritis drugs was projected to reach $30.5 billion in 2019, with TNF-α inhibitors accounting for a 71.1% market share. Currently, the TNF-α inhibitors widely used in clinical practice are primarily large-molecule biologics, including adalimumab, etanercept, infliximab, certolizumab, and golimumab.

Sina Medicine, based on financial report data, notes that adalimumab, etanercept, and infliximab, as the three best-selling TNF-α inhibitors currently, continue to demonstrate strong performance in the global market. In 2018, among the top 10 global pharmaceutical sales rankings, adalimumab topped the list with $19.936 billion in sales, etanercept ranked seventh with $7.126 billion, and although infliximab’s sales declined, they still reached $6.446 billion.

Domestic Market: Originator Drugs Struggle Against Local Biosimilars

Currently, there are 8 biologic drugs marketed in China for autoimmune diseases, including 5 imported drugs and 3 domestically produced drugs, all of which are biosimilars. Among them, 3SBio’s “Yisaipu (Etanercept)” was the first to be launched in 2005, becoming the first biosimilar accepted by the market. As shown in the table below:

After the aforementioned originator product entered the Chinese market, its market penetration remained suboptimal due to a series of factors. Taking Qilu Pharmaceutical’s etanercept biosimilar, currently under application for marketing approval, as an example, the domestically produced “Yisaipu” from 3SBio holds a first-mover advantage and was included in the National Reimbursement Drug List in 2017, thereby securing a dominant position in the fields of rheumatoid arthritis, ankylosing spondylitis, and psoriasis.

With the market launch of ‘Qiangke’, ‘Anbinuo’, and Qilu Pharmaceutical’s etanercept biosimilar, the market share of the originator drug ‘Enbrel’ will be gradually eroded.

It cannot be ignored that although rheumatoid arthritis and ankylosing spondylitis represent a huge market in China, the market share of biologic drugs remains small due to low patient awareness and low market penetration of these agents. Meanwhile, Qilu Pharmaceutical and later entrants face even fiercer market competition, and the survival of their products will be subjected to rigorous tests.

What Are the Opportunities for Latecomers in TNF-α Monoclonal Antibodies? Sina Medicine Has Previously Explored This Topic (See Details: Latest Advances in TNF-α Antibody R&D and the Market Landscape of Domestic Biologic Large Molecules in the Autoimmune Field)

In this field, imported and domestically produced varieties are mixed; therefore:

a) For products in the marketing application stage, such as Qilu Pharmaceutical’s etanercept biosimilar, which face intense competition from “Yisaipu,” “Enbrel,” “Qiangke,” and “Anbinuo,” pricing is a critical promotional strategy and market entry point. Securing comprehensive national medical insurance coverage, along with deeper patient access programs, discounts, and insurance benefits, is of paramount importance.

b) For products in the early clinical stages, greater emphasis should be placed on product safety, improved patient compliance, and the development of more differentiated products.