On July 15, Hengrui Medicine disclosed the positive top-line results of its GLP-1/GIP dual receptor agonist HRS9531 in China's Phase III weight loss study. The average weight loss in the 6mg dose group was 19.2% in 48 weeks, and it did not reach the plateau. At the same time, the safety is good, and Hengrui plans to submit a new drug application in the near future.

Not long ago, Innovent Biologics' GLP-1/GCG dual receptor agonist Xinermei® (Masdu peptide) was approved for marketing in China for adult weight control. Its Phase III clinical trial showed that at week 48, the average weight loss in the 6 mg group reached 14.84%.

The GLP-1 products of the two major pharmaceutical companies, Innovent and Hengrui, have entered the harvest period one after another, and the domestic weight loss drug market has ushered in a new pattern.

Average weight loss of 19.2% in 48 weeks

HRS9531 (KAI-9531) is a dual receptor agonist of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) independently developed by Hengrui Medicine.

HRS9531-301 is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical study (NCT06396429) designed to evaluate the efficacy and safety of HRS9531 injection in Chinese adult subjects with obesity (BMI ≥ 28 kg/m2) or overweight (BMI ≥ 24 kg/m2) with at least one weight-related comorbidity.

A total of 567 subjects were enrolled in the study, with an average baseline weight of 93 kg. Subjects were randomly divided into groups in a 1:1:1:1 ratio and received HRS9531 injection 2mg, 4mg, 6mg or placebo once a week. The co-primary endpoints were the percentage of weight change from baseline after 48 weeks of administration and the proportion of subjects with a weight reduction of ≥5% from baseline.

Among them, 531 subjects completed the study. Compared with placebo, all dose groups of HRS9531 achieved superiority in the co-primary endpoints and all key secondary endpoints, and the overall safety was similar to that reported in previous trials.

The results of the primary analysis (treatment strategy) showed that after 48 weeks of treatment with HRS9531 injection, the average weight loss was up to 17.7% (16.3% after placebo adjustment), and the proportion of subjects with a weight loss of ≥5% reached 88.0%. In addition, 44.4% of subjects in the high-dose group had a weight loss of ≥20%. The results of the supplementary analysis (hypothetical strategy) showed that the average weight loss in the HRS9531 treatment group was up to 19.2% (17.7% after placebo adjustment).

HRS9531 showed good safety and tolerability, which was consistent with other GLP-1 drug treatments and previously reported Phase II clinical data for HRS9531. Most treatment-emergent adverse events (TEAEs) were mild to moderate, mainly gastrointestinal-related events.

It is worth mentioning that in May 2024, Hengrui Medicine licensed the exclusive rights to develop, produce and commercialize three GLP-1 innovative drugs (HRS9531, HRS-7535, HRS-4729) worldwide, excluding Greater China, to Kailera Therapeutics in the NewCo model. The initial payment plus milestone payments can total up to US$6 billion, and the company also acquired a 19.9% stake in Kailera.

Hengrui Medicine plans to submit a new drug application (NDA) for HRS9531 injection for long-term weight management in China in the near future, and Kailera is advancing the global clinical development of HRS9531 (KAI-9531).

Fierce competition among GLP-1/GIP dual receptor agonists

Eli Lilly's tirpotide is the world's first GLP-1/GIP dual receptor agonist. It was approved by the US FDA for the treatment of type 2 diabetes (T2DM) in May 2022 and for weight loss in November 2023. In China, both indications of tirpotide have also been approved for marketing.

The FDA's approval is based on data from two Phase III clinical trials, SURMOUNT-1 and SURMOUNT-2. In SURMOUNT-1, the average weight loss after 72 weeks of treatment with 15 mg of tebuconazole was 20.9% (24 kg), and the proportion of patients who lost more than 5% was 96%. In SURMOUNT-2, the 15 mg group lost 15.7% (24 kg), and the proportion of patients who lost more than 5% was 86.4%.

In 2024, the combined sales of the two brands of telportolide will reach US$16.466 billion, second only to semaglutide and K drug.

However, competition in the GLP-1/GIP dual receptor agonist market will soon enter a fierce stage.

In April 2025, the innovative weight loss drug Sejaro from Russian pharmaceutical company Geropharm was approved for marketing in Russia. It is reported that the drug is completely bioequivalent to telportin. However, the original telportin has not yet been approved in Russia for the treatment of obesity and diabetes indications.

Among the GLP-1/GIP dual receptor agonists under development, many in China have entered Phase III clinical trials, including Hengrui Medicine, Zhongsheng Pharmaceutical, Borri Pharmaceutical, Hansoh Pharmaceutical, etc., and there are more in Phase II clinical trials and earlier stages, and the competition landscape is becoming increasingly fierce.

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