Kailera and Hengrui's Oral GLP-1 Candidate HRS-7535 Hits Phase 3 Efficacy but Sparks GI Tolerability Concerns

Kailera and Hengrui's Oral GLP-1 Candidate HRS-7535 Hits Phase 3 Efficacy but Sparks GI Tolerability Concerns

On July 7, 2026, newly public biotechnology firm Kailera Therapeutics and its China-based partner, Jiangsu Hengrui Pharmaceuticals, reported positive topline Phase 3 results in China for their experimental oral small-molecule GLP-1 receptor agonist, HRS-7535 (KAI-7535), in obesity and Type 2 diabetes.

While the drug successfully hit its primary weight loss and blood sugar reduction endpoints, the clinical data sparked significant concerns regarding its safety and tolerability profile¹, causing Kailera’s stock to slide.

Efficacy in Obesity (HARBOR-1 Trial)

In the 44-week Phase 3 HARBOR-1 trial in China, which randomized patients with obesity:

• The highest daily dose tested (180 mg) achieved a mean weight loss of 10.9% (efficacy estimand) and 9.8% (treatment-policy estimand) from baseline, compared to just 2.5% for the placebo arm.
• This weight loss is numerically comparable to next-generation oral weight-loss pills currently in development, such as Eli Lilly’s oral GLP-1 Foundayo (orforglipron) and Novo Nordisk’s Wegovy pill, especially considering that China-based trials historically enroll patients with lower baseline body-mass indexes (BMIs).

Severe Gastrointestinal Side Effects

Despite the encouraging efficacy, analysts and investors were "alarmed" by the high rates of gastrointestinal (GI) side effects observed in the trial:

• Nausea: Testing revealed that 70% of recipients experienced nausea.
• Vomiting: Between 67% and 69% of patients reported vomiting.
• Diarrhea: The drug also carried a high diarrhea rate (~36%).
• Comparison: William Blair analyst Andy Hsieh noted that these totals are significantly higher than competitive assets, adding: "In our view, reducing the rate of nausea and vomiting to roughly mid-30% and mid-20%, respectively, will yield a competitive profile."

On the positive side, HRS-7535 showed no signs of liver toxicity, which is a major regulatory concern for oral small-molecule GLP-1 drugs (such as Pfizer’s now-shelved danuglipron).

Next Steps and Dosing Adjustments

To address these severe tolerability issues, Kailera is shifting its strategy in an ongoing global Phase 2 trial. The company is starting patients with a much lower initial dose to allow for more gradual titration and is exploring a "nighttime" dosing cohort to mitigate the severity of nausea and vomiting.