Partners Hengrui Pharma and Kailera Therapeutics announced on July 7 that two late-stage clinical trials in China evaluating an investigational small molecule GLP-1 receptor, known as HRS-7535 or KAI-7535, achieved their primary endpoints. Hengrui said it plans to submit new drug applications for obesity and type 2 diabetes in China following these results.
In the Phase 3 HARBOR-1 trial among adults with obesity or overweight, patients receiving 120 mg and 180 mg of the oral treatment saw mean weight loss of 8% and 9.8% from baseline at week 44, compared to a 2.4% reduction with placebo. William Blair analysts said the data is competitive but noted that average weight loss was lower than that observed with Eli Lilly’s Foundayo. The analysts also commented that China-specific trials tend to show less profound weight loss due to differences in body mass index and participant demographics.
Safety findings indicated most treatment-emergent adverse events were mild to moderate gastrointestinal issues. Nausea occurred in about 70% of patients treated with HRS-7535 versus 16.2% on placebo; vomiting affected up to 68.6%, and diarrhea up to 36.9%. Discontinuation rates due to adverse events ranged from approximately three percent in the active arms to under three percent with placebo. No liver safety signals were reported, according to the company.
William Blair analysts said they are “particularly alarmed” by the nausea and vomiting rates seen in this study compared with earlier phase research, stating, “In our view, reducing the rate of nausea and vomiting to roughly mid-30% and mid-20%, respectively, will yield a competitive profile.” Kailera Chief Medical Officer Scott Wasserman said, “To optimize KAI-7535’s overall clinical profile for the treatment of obesity in diverse patient populations, we are assessing a wide dose range, a lower starting dose, and a more gradual titration in our ongoing Phase 2 global clinical trial.”
The OUTSTAND-2 study met its main goal by demonstrating non-inferiority against dapagliflozin (Farxiga) for type 2 diabetes after thirty-two weeks at multiple doses daily; patients receiving the highest dose had an HbA1c reduction of 1.68%, while those on dapagliflozin saw a decrease of 1.28%. Improvements were also reported for body weight, blood pressure, lipid profiles, and urinary albumin-to-creatinine ratio.
William Blair concluded, “Taken together, we believe KAI-7535’s efficacy has the potential to be competitive in both chronic weight management and type 2 diabetes.” The company plans further disclosures at upcoming conferences.
