Financial Services Association, November 19 (Reporter He Fan) In the face of the increasingly competitive GLP-1 drug circuit, how can pharmaceutical companies use innovative breakthroughs to overcome and at the same time truly address clinical needs in terms of new mechanisms and technology? At the GLP-1 Drug Symposium (Chengdu) held today, participants discussed global GLP-1 drug development trends.

Some industry insiders revealed at the conference that in addition to type 2 diabetes and weight loss indications, various indications are being developed and may expand into fields such as PCOS (polycystic ovary syndrome) and stroke in the future. Furthermore, triple-target drugs GLP (glucose-like peptide-1), GIP (glucose-dependent insulin-releasing peptide), and GCG (glucagon) have begun to rise, and multi-target combinations may achieve the best curative effect in treating metabolic diseases.

Various indications are under continuous development

In September, the Lasker Prize, known as the “Nobel Prize weather vane,” awarded the Clinical Medical Research Award to three scientists who discovered and developed GLP-1 drugs. In recent years, GLP-1 receptor agonists have made continuous breakthroughs as a highly sought-after new category around the world, attracting many domestic and foreign pharmaceutical companies to step up their layout.

How is the global clinical development of GLP-1 drugs progressing? At the GLP-1 drug seminar held today, Zhang Lin, head of Renhui Biomedical Department, said, “Judging from weight loss indications, GLP-1 drugs show a trend that is more suitable for the development of weight-related complications in the Chinese population.” However, when using GLP-1 drugs to lose weight or cause muscle loss, data showed that in clinical studies of simeglutide, liraglutide, and tirpotide, muscle loss accounted for 40%, 30%, and 25% of total body weight loss, respectively. “Therefore, targets for fat loss and muscle building will become a new arena. ActRII (activin type II receptor) is currently receiving much attention.”

According to reports, LAE102, an ActrII (02105.HK) drug indicated for obesity and metabolic diseases, is in clinical phase I; Eli Lily/Versanis is indicated for obesity and type 2 diabetes; and monoclonal antibody drugs targeting ActrIA/b are in clinical phase II.

In addition, many pharmaceutical companies are developing indications other than type 2 diabetes and obesity. In addition to cardiovascular disease, chronic kidney disease, NASH (non-alcoholic steatohepatitis), OSAS (obstructive sleep apnea syndrome), and neurodegenerative diseases, Zhang Lin also specifically mentioned PCOS. As a common reproductive endocrine disease among women of childbearing age, PCOS is clinically highly heterogeneous, showing complications such as hyperandrogenemia, hirsutism, acne, and insulin resistance. It is estimated that the number of women of childbearing age nationwide is 24 million. Weight loss treatment has significant clinical significance for patients with PCOS and obesity. The data shows that PCOS patients lose 5%-10% of their body weight and can improve menstrual cycle, ovulation, and insulin resistance. PCOS patients without ovulation who are overweight or obese lose 5% of their body weight, and pregnancy rate increases from 0 to 30%. GLP-1 drugs have great potential in PCOS and other fields.

Three-target GLP-1 drugs may become a research trend

On July 19, Eli Lilly announced that the dual-target GLP-1 drug Mofengda (terpotide injection) was approved for marketing in China. With the exception of tiverpotide, GLP-1 drugs currently approved for weight loss in China are single-target drugs.

“There is still room for improvement in facial fat protection, stronger weight loss and sugar reduction, less rebound from drug withdrawal, and muscle protection.” Song Wenxin, deputy general manager of Minwei Biotech, a subsidiary of Lepu Healthcare (300003.SZ), believes that in the “post-terpotide” era, high-quality weight loss must take a two-pronged approach. On the one hand, in a negative energy state, GLP-1R agonists and GIPR agonists can maintain physiological function passively mobilizing tissues that are relatively easy to consume. On the other hand, thyroxine, Glucagon (glucagon), and FGF21 can increase basal metabolic rate. Therefore, a three-target GLP drug combining GLP-1R, GIPR, and Glucagon can relatively gently suppress appetite while gently increasing basal metabolic rate.

Currently, the GLP-1 three-target drug, which is currently being developed the fastest, is retatrutide, a GLP/GIP/GCG triple agonist developed by Eli Lilly, and has advanced to phase III clinical trials.

“The multi-target combination of intestinal insulin is likely to achieve optimal efficacy in treating metabolic diseases.” Gan Yulong, senior clinical operation director of Doyle Biotech, a subsidiary of East China Pharmaceutical (000963.SZ), said at the seminar that GLP/GIP/GCG three-target drugs can use fatty acid chain modification technology similar to liraglutide in the production process, and the production cost is extremely low, but it is very challenging to select three specific innovative biopharmaceuticals that can be active against GLPR/GIPR/GCGR. It is very challenging to find a balance between pharmacodynamics, cross-species properties, immunogenicity, safety and stability.