First Domestic Semaglutide Biosimilar Files for Approval in China, But Weight-Loss Use Remains Distant

In the current booming development of GLP-1 drugs, the veteran players in the hypoglycemic fieldHuadong MedicineHas a wealth of pipelines in reserve and is one of the companies in China that cannot be ignored. In addition to the liraglutide biosimilar (trade name: Lilupin) approved for weight loss in July 2023, the company also has other pipelines in clinical stages, including semaglutide biosimilar, innovative drugs HDM1002, DR10624, HZ012, and HDM1005.

Among these, in the biosimilar drug of semaglutide, the products of Sinopharm Huadong and Hangzhou Jiuyuan Gene Engineering Co., Ltd. have both reached Phase 3 clinical trials. The new drugs DR10624 and HZ012 are products of Zhejiang Doer Biologics. Huadong Medicine, through its wholly-owned subsidiary Sinopharm Huadong, holds 75% of Doer Biologics and 21.06% of Jiuyuan Gene Engineering. In addition, Huadong Medicine is the single largest shareholder of Jiuyuan Gene Engineering. In January this year, Jiuyuan Gene Engineering also submitted its prospectus to the Hong Kong Stock Exchange, initiating its IPO.

Currently, there has been new progress in the aforementioned pipeline. On April 3, the official website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) showed that the New Drug Application (NDA) for the biosimilar of semaglutide injection (JY29-2) developed by Hangzhou Jiuyuan Gene Engineering Co., Ltd. has been accepted. This marks the first China-produced semaglutide to apply for marketing authorization.

Semaglutide is one of the star products in the GLP-1 field today, developed by the Danish pharmaceutical company Novo Nordisk. In 2023, the sales of its Type 2 diabetes indication injectable formulation Ozempic, oral formulation Rybelsus, and weight loss indication injectable formulation Wegovy reached $13.889 billion, $2.720 billion, and $4.548 billion respectively, totaling $21.157 billion, which is already close to the revenue level of $21.2 billion for Humira, the global top-selling drug in 2022.

However, it is worth noting that this JY29-2 application is for the Type 2 diabetes indication (trade name: Jiyoutai), while its weight loss indication (trade name: Jikeqin) was just approved for clinical trials in January this year. As for future commercialization, it remains to be seen whether Hangzhou Jiuyuan Gene Engineering Co., Ltd. will directly face competition from Huadong Medicine or will entrust the product to the latter for sales.

In fact, following the GLP-1 products popularized by Novo Nordisk and Eli Lilly, there are quite a few domestic companies in China working on biosimilars and improved new drugs of semaglutide.

DXY Insight database shows that, in addition to the aforementioned companies, Chengdu Bright:Aimek, Zhongshan Taiqing, Shijiazhuang Pharmaceutical Group, SiHuan Pharmaceutical, Qilu Pharmaceutical, Chongqing Chenan Biotechnology, United Laboratories,Livzon GroupAll have products in Phase 3 clinical trials, but the indications are all concentrated on Type 2 diabetes. Only Aimeike's product, introduced from Beijing Zhibiao Biotechnology, is in Phase 1 clinical trials for weight loss indications. In other words, it will take some time before domestically produced semaglutide can be compliantly used for weight loss.

An industry insider analyzed to The Paper that this is mainly because the weight-loss indication of the original semaglutide has not yet been approved in China. Domestic companies are facing issues related to clinical design and costs, as well as considerations regarding the registration pathway.

On April 1 this year, the CDE (Center for Drug Evaluation) released the "Guiding Principles for Clinical Trial Design of Semaglutide Injection Biosimilar for Weight Management Indication (Draft for Comments)", providing recommendations and requirements regarding specific issues that need attention during its clinical development.

Currently, the type 2 diabetes indication for Novo Nordisk's semaglutide was approved in China in 2021. The company also revealed in March this year that its weight loss indication is expected to be approved for marketing in China this year. Meanwhile, its strong competitor, Eli Lilly's tirzepatide, had its NDAs for these two indications accepted by the CDE in September 2022 and August 2023, respectively.

Moreover, the iteration speed of products in the GLP-1 field is very fast, and it is unlikely that domestic medical insurance will cover the cost for weight loss indications. In other words, this tests the product selection and commercialization capabilities of the companies entering the market.

In 2023, the weight-loss drug Tirzepatide (brand name: Zepbound) generated sales of $175.8 million within just one month of its launch. It is the world's first and currently only dual-target agonist for GIPR/GLP-1R, with weight-loss effects superior to Semaglutide. Adding to this, the sales of its Type 2 diabetes indication (brand name: Mounjaro) reached $5.163 billion, bringing the total annual sales of the drug in 2023 to $5.339 billion.

According to forecasts by data and analytics company GlobalData, tirzepatide will surpass semaglutide to become the best-selling drug in the diabetes and weight loss field, with sales reaching $27 billion by 2029. In other words, for companies in China, if they choose a follower strategy, the key issue is which company’s product to closely follow, in order to maximize the time gap between product iterations and capture a share of the market.

In addition, the "competition" among leading companies in multiple products not only reveals a huge market demand for latecomers but also reflects breakthrough directions in the GLP-1 field, such as long-acting, oral administration, multi-targeting, combination therapy, and multi-indication benefits.

Therefore, many Chinese players, including Huadong Medicine, have also chosen to develop new drugs. As mentioned earlier, HDM1002 is a small-molecule drug targeting GLP1R, while HZ012 and HDM1005 are peptide drugs that target both GLP1R and GIPR. All three of these drugs are in Phase 1 clinical trials for Type 2 diabetes and weight loss indications. DR10624, on the other hand, is an antibody fusion protein targeting GLP1R, GCGR, and FGF21, and is currently undergoing Phase 1 clinical trials for weight loss indications.

In addition, BGM0504 from BrightGene BioMedical, HS-20094 from Jiangsu Hengrui Pharmaceuticals,Hengrui MedicineHRS9531, developed by Huadong Medicine, is a novel dual-target peptide drug for GLP1R/GIPR, currently in Phase 2 clinical trials for the aforementioned two indications.Dongyang LightHEC88473, a biologic drug, is an antibody fusion protein targeting GLP1R/FGF21. It is currently in Phase 2 and Phase 1 clinical trials for type 2 diabetes and weight loss, respectively.

Among these, the frontrunner is Mastytide, a GCGR/GLP-1R dual-target new drug introduced by Innovent Biologics from Eli Lilly. Its weight loss indication was accepted by the CDE in February this year. The drug's Type 2 diabetes indication is currently in Phase 3 clinical trials.

Editor: He Junxi