Announcement • Jul 07
Kailera Therapeutics Announces Positive Topline Data From Two Hengrui Pharma Phase 3 Clinical Trials Of Oral Small Molecule GLP-1 Receptor Agonist HRS-7535/KAI-7535
Kailera Therapeutics, Inc. announced positive topline data from two additional Phase 3 clinical trials of oral small molecule GLP-1 receptor agonist HRS-7535 (also known as KAI-7535) conducted by Hengrui Pharma: the Phase 3 HARBOR-1 trial (NCT06904105) in adults living with obesity/overweight in China and the Phase 3 OUTSTAND-2 trial (NCT06589765) in adults with type 2 diabetes (T2D) in China. Kailera is concurrently advancing KAI-7535 in a global Phase 2 clinical trial in people living with obesity or overweight. The trial initiated in April 2026, with data expected in 2027. HRS-7535 (being developed by Kailera as KAI-7535) is a small molecule GLP-1 receptor agonist, which was designed to improve upon the clinical profile of existing oral treatments. It was developed by Hengrui Pharma and licensed to Kailera outside of Greater China in 2024. Over 2,000 patients to date have been dosed with HRS-7535 in clinical trials in China. Kailera is conducting a global Phase 2 trial of KAI-7535 for the treatment of obesity, with data expected in 2027. The KAI-7535 Phase 2 global trial is a multicenter, randomized, double-blind, placebo-controlled conducted by Kailera in the U.S. and Australia. This trial is designed to further optimize KAI-7535's clinical profile for the treatment of obesity by evaluating a wide range of doses, starting at a lower dose of 15 mg, and following a more gradual titration schedule. The trial initiated in April 2026 and is expected to enroll approximately 320 adult participants with a BMI of 30 or greater, or a BMI of 27 or greater with at least one co-morbidity, which may include T2D. Participants are enrolled across four parallel cohorts (each N=80, randomized 4:1 active to placebo), including two dosing regimens (morning and evening). Participants receive escalating doses of KAI-7535 or placebo over a 44-week treatment period. The trial incorporates a stepwise titration schedule designed to improve tolerability and determine the optimal balance between weight loss and tolerability. All active-treatment participants initiate therapy at 15 mg and increase every four weeks, reaching a maximum dose of 180 mg. A higher-dose cohort follows an extended escalation schedule, with the option to further increase to 360 mg or remain at the maximum tolerated dose. The primary endpoint is percent change in body weight from baseline at Week 44. HARBOR-1 met its primary endpoint, achievement of superior weight reduction at Week 44 with HRS-7535 compared to placebo. Based on the efficacy estimand, participants taking HRS-7535 120 mg and 180 mg achieved a mean weight loss of 9.5% and 10.9% from baseline at Week 44, respectively, compared to 2.5% with placebo. Based on the treatment policy estimand, participants taking HRS-7535 120 mg and 180 mg achieved a mean weight loss of 8.0% and 9.8% from baseline at Week 44, respectively, compared to 2.4% with placebo. Based on the treatment policy estimand, at Week 44, 58.6% (120 mg) and 68.2% (180 mg) of HRS-7535 treated participants achieved at least 5% weight loss; 39.6% (120 mg) and 46.6% (180 mg) achieved at least 10% weight loss; and 18.5% (120 mg) and 26.0% (180 mg) achieved at least 15% weight loss. At Week 50, based on an ad hoc analysis, participants taking HRS-7535 120 mg and 180 mg achieved a mean weight loss of 9.5% and 11.1% from baseline, respectively, compared to 2.6% with placebo, based on the efficacy estimand. Improvements were also observed in Hba1c, systolic blood pressure, and lipid profiles. Most treatment-emergent adverse events (TEAEs) were mild to moderate and gastrointestinal-related. The most common TEAEs for participants treated with HRS-7535 (120 mg and 180 mg, respectively) were nausea (70.3% and 70.0% vs. 16.2% with placebo); vomiting (66.7% and 68.6% vs. 4.5% with placebo); and diarrhea (36.9% and 35.9% vs. 15.3% with placebo). Treatment discontinuation rates due to TEAEs were 4.1% (120 mg) and 3.1% (180 mg) for HRS-7535 vs. 2.7% with placebo. No liver safety signal was observed, consistent with prior HRS-7535 clinical trials. HARBOR-1 (HRS-7535-303, NCT06904105) was a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial conducted by Hengrui in China to evaluate the efficacy and safety of HRS-7535 in adults with overweight or obesity. The trial enrolled 556 adults with obesity with a mean baseline body weight of 94.1 kg and mean baseline body mass index (BMI) of 34.0 kg/m2. The participant population was 62% female. Participants were randomized (2:2:1) to receive once-daily HRS-7535 120 mg, 180 mg, or placebo. The primary objective was to evaluate the efficacy of HRS-7535 compared to placebo in the percentage change in body weight at Week 44. Following the primary endpoint assessment, participants continued treatment through Week 50, the end of the trial. OUTSTAND-2 met its primary endpoint, non-inferiority to dapagliflozin across all HRS-7535 dose levels (30 mg, 60 mg, and 90 mg) at Week 32, with the HRS-7535 90 mg group demonstrating significant HbA1c reduction compared to dapagliflozin. At Week 32, based on the efficacy estimand, the reductions in HbA1c from baseline for the HRS-7535 30 mg, 60 mg, and 90 mg groups and the dapagliflozin 10 mg group were 1.58%, 1.50%, 1.68%, and 1.28%, respectively. Improvements were observed in body weight, systolic blood pressure, lipid profiles, and the urinary albumin-to-creatinine ratio (UACR). Most TEAEs were mild to moderate and gastrointestinal-related. No Grade 3 hypoglycemic events were reported, and, consistent with prior HRS-7535 clinical trials, no liver safety signal was observed. OUTSTAND-2 (HRS-7535-302, NCT06589765) was a multicenter, randomized, double-blind, dapagliflozin-controlled Phase 3 trial conducted by Hengrui Pharma in China. It aims to evaluate the efficacy and safety of HRS-7535 in adults with type 2 diabetes who have inadequate glycemic control despite metformin therapy. The trial enrolled 810 adults with type 2 diabetes with a mean baseline HbA1c of 8.60%, mean baseline body weight of 74.7 kg and mean baseline body mass index (BMI) of 27.1 kg/m2. The participant population was 36% female. Participants were randomized in a 1:1:1:1 ratio to receive once-daily oral treatment with HRS-7535 (30 mg, 60 mg, or 90 mg) or dapagliflozin (10 mg). The core treatment period was 32 weeks, after which all participants entered an extended treatment period continuing through Week 52. The primary endpoint was change in HbA1c from baseline at Week 32. Hengrui Pharma intends to share the full HARBOR-1 and OUTSTAND-2 clinical trial data at upcoming scientific conferences and plans to submit NDAs for HRS-7535 for the treatment of T2D and obesity in China.
