New data on Hengrui Pharma and Kailera Therapeutics’ investigational oral GLP-1 have validated the late-stage weight loss asset and paved the road for a regulatory submission in China, but analysts pointed to high rates of nausea and vomiting that could challenge the ongoing U.S. study.
Partners Hengrui Pharma and Kailera Therapeutics revealed Tuesday that two China-based late-stage trials evaluating an investigational small molecule GLP-1 receptor have hit their main goals, prompting Hengrui to tee up plans for regulatory submission in the Asian country.
Meanwhile, analysts say Kailera will have to overcome high rates of gastrointestinal side effects in its ongoing U.S. trial if it is to establish a competitive profile. The biotech owns the rights to the obesity candidate outside of China.
The asset, called HRS-7535—or KAI-7535 by Kailera—is designed to improve upon the clinical profile of existing oral treatments. If approved, it would be the third oral GLP-1 for obesity to hit the U.S. market, following Novo Nordisk’s Wegovy pill and Eli Lilly’s Foundayo earlier this year.
In the Phase 3 trial called HARBOR-1, Hengrui tested HRS-7535 among adults with obesity or overweight. At week 44, the experimental oral treatment demonstrated a mean weight loss of 8% and 9.8% from baseline for patients receiving 120 mg and 180 mg, respectively. That’s compared to the 2.4% reduction experienced in the placebo arm and represents a primary endpoint win.
Analysts at William Blair see the data as competitive, despite average weight loss coming in below that of Lilly’s Foundayo. The analysts in a Tuesday note caveated that China-specific trials “tend to generate less profound weight loss relative to global studies, primarily driven by lower BMI and higher proportion of male participants (though we recognize that the proportion of females was similar between HARBOR-1 and ATTAIN-1).”
After this data drop, Hengrui said it plans on submitting new drug applications (NDAs) in both obesity and type 2 diabetes in China, according to a Tuesday release. Back in May, the partners shared plans for a China regulatory submission in type 2 diabetes after unveiling positive results from the Phase 3 OUTSTAND-1 study.
When looking at safety, most of the treatment-emergent adverse events (TEAEs) were mild to moderate in severity and gastrointestinal-related, according to the company.
The most common TEAEs were nausea, occurring in about 70% of patients treated with HRS-7535 compared to 16.2% on placebo. Up to 68.6% of patients receiving HRS-7535 experienced vomiting and up to 36.9% experienced diarrhea.
Treatment discontinuation rates due to TEAEs were 4.1% for patients receiving 120 mg, 3.1% for the180-mg cohort and 2.7% in the placebo arm. No liver safety signal was observed, the company said, with plans to release the full dataset at an upcoming conference.
Gastrointestinal adverse events occurred more frequently than in the Phase 2 China study, with analysts at William Blair writing that they are “particularly alarmed” by the nausea and vomiting rates.
“In our view, reducing the rate of nausea and vomiting to roughly mid-30% and mid-20%, respectively, will yield a competitive profile,” William Blair said Tuesday. Kailera will have to demonstrate that reduction in an ongoing midstage study of the candidate for people with obesity and overweight, with a readout expected next year.
“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,” Kailera Chief Medical Officer Scott Wasserman said in a prepared statement.
The other late-stage findings come from OUTSTAND-2, which achieved its main goal by demonstrating non-inferiority to dapagliflozin—commonly sold as Farxiga—among participants with type 2 diabetes at 32 weeks. The study evaluated HRS-7535 at three dose levels delivered daily.
Compared to baseline, patients who received the highest HRS-7535 dose of 90 mg demonstrated an HbA1c reduction of 1.68%. Meanwhile, participants receiving 10 mg of dapagliflozin demonstrated a HbA1C lowering of 1.28%. Hengrui also reported improvements in body weight, systolic blood pressure, lipid profiles and the urinary albumin-to-creatinine ratio.
William Blair views the HbA1c lowering as competitive to 14 mg of Novo’s Rybelsus (semaglutide), which demonstrated up to 1.64% reduction in a subset of Chinese patients for its Phase 3 program.
No liver safety signals were observed, and no Grade 3 hypoglycemic events occurred, according to the company.
“Taken together, we believe KAI-7535’s efficacy has the potential to be competitive in both chronic weight management and type 2 diabetes,” William Blair analysts wrote.
The asset is one of Kailera’s four clinical candidates, with the biotech’s late-stage program—an injection called ribupatide—leading the way. Kailera’s weight loss pipeline fueled its $625 million IPO in April, which served as the industry’s largest public debut at the time.
“From a stock perspective, we view Kailera’s broad GLP-1-based pipeline as largely de-risked through clinical and commercial validation from competitor programs, especially those from Eli Lilly,” William Blair concluded.
