Hengrui and Kailera report 19.2% weight loss from Chinese Phase 3 of HRS9531

Hengrui Pharma and its U.S. partner Kailera Therapeutics reported new results from a Phase 3 obesity trial in China of HRS9531, a once-weekly injectable drug that acts on two hormone receptors, GLP-1 and GIP. In the 48-week study, called GEMINI-1, people taking the highest tested dose, 6 mg, lost an average of 19.2% of their body weight, with no sign that weight loss had leveled off by the end of the trial ^[1].

The trial enrolled 567 adults in China with obesity or overweight plus at least one weight-related health problem, and did not include people with diabetes. Participants had an average starting weight of about 93 kg, or 205 pounds ^[1]. They were randomly assigned to receive placebo or one of three doses of HRS9531: 2 mg, 4 mg or 6 mg, once a week.

Using one way of measuring results that counts only people who stayed on treatment as planned, average weight loss was 11.2% at 2 mg, 17.4% at 4 mg and 19.2% at 6 mg, compared with 1.4% for placebo ^[1]. A second, more conservative method, which counts everyone regardless of whether they stopped treatment early, showed slightly lower numbers: 10.7%, 16.4% and 17.7% for the three doses ^[1]. By that same measure, 85.7% of people on the 6 mg dose lost at least 5% of their body weight, and 44.4% lost at least 20% ^[1].

Side effects were mostly mild-to-moderate stomach and digestive problems, similar to what has been seen with other GLP-1 drugs, and few people quit the trial because of side effects: 0.7% at 2 mg, 0.7% at 4 mg, 1.4% at 6 mg, and none in the placebo group ^[1]. The companies also reported improvements in blood pressure, cholesterol levels, insulin resistance markers and an inflammation marker called hsCRP among those taking the drug ^[1]. Hengrui has submitted an application to China's National Medical Products Administration to market HRS9531 for weight management, and that application has been accepted for review ^[1].

These results build on an earlier, smaller Phase 2 trial in China that tested an even higher dose, 8 mg, and found 23.6% average weight loss at 36 weeks, also with no plateau ^[1]. Kailera, which holds rights to develop the drug outside Greater China under the name KAI-9531, plans to start global Phase 3 trials by the end of 2025. Those trials will test higher doses, including 8 mg and 10 mg, over longer treatment periods, and will include separate studies for people with obesity alone, people with obesity and type 2 diabetes, and people with more severe obesity ^[1].

Why it matters for patients

These results come from a Chinese trial and a Chinese regulatory filing, not from a U.S. study or an application to the Food and Drug Administration. HRS9531 is not approved or available in the United States, and the global Phase 3 program that could support a future U.S. application has not yet started ^[1]. The 19.2% weight-loss figure is an average from one dose in one trial; individual results varied, and the companies used two different statistical methods that produced somewhat different numbers ^[1]. Side effect data so far look similar to other approved GLP-1 drugs, mostly digestive symptoms, but the safety picture over longer use and in more diverse patient groups is still being gathered ^[1].

What happens next

Hengrui's marketing application is now under review by Chinese regulators, though no decision date has been announced ^[1]. Kailera has said it plans to begin global Phase 3 trials of the drug, testing higher doses and longer treatment, before the end of 2025 ^[1]. Those trials would need to produce their own results before any U.S. regulatory filing could follow.