Ribupatide

Fresh off one of the largest biotech IPOs on record, Kailera Therapeutics on Tuesday reported positive topline results from two Phase III trials in China of oral GLP-1 receptor agonist HRS-7535, known outside China as KAI-7535.The studies, conducted by partner Jiangsu Hengrui Pharmaceutical Co., successfully hit their main goals in both obesity and type 2 diabetes, adding late-stage evidence for the asset's effectiveness. Kailera, which licensed the drug from Hengrui outside China in 2024, is now evaluating it in its own global Phase II weight-loss trial.Weight loss around 11%One of the studies reported Tuesday, known as HARBOR-1, enrolled 556 adults with overweight or obesity and compared once-daily oral HRS-7535 with placebo over 44 weeks as the main goal. Patients on the higher 180-mg dose lost an average 10.9% of their body weight under the efficacy estimand analysis, versus 2.5% for placebo, while the 120-mg dose produced 9.5% weight loss.Based on the treatment policy estimand – which captures the effect of being assigned to treatment, regardless of whether people stay on the course – those in the 180-mg dose arm shed 9.8% of their body weight at 44 weeks, while the 120-mg group lost 8%.An ad hoc analysis at the 50-week mark showed weight loss reaching 11.1% and 9.5% with the higher and lower doses, respectively, based on the efficacy estimand. The trial also reported improvements in HbA1c, systolic blood pressure and lipid profiles.Gastrointestinal (GI) events such as nausea (about 70%), vomiting (about 67%) and diarrhoea (about 36.5%) accounted for most of the side effects, which were typically mild-to-moderate in nature. Treatment discontinuations due to side effects were under 5% at both doses, and investigators reported no liver safety signal.The second trial, OUTSTAND-2, enrolled 810 adults with type 2 diabetes inadequately controlled on metformin and compared three doses of HRS-7535 with AstraZeneca's Farxiga (dapagliflozin). The study met its primary endpoint as well, demonstrating non-inferiority across all dose groups at week 32, while the highest 90-mg dose achieved significant HbA1c reduction against Farxiga. Average HbA1c reductions ranged from 1.50% to 1.68% across HRS-7535 doses, compared to 1.28% for Farxiga.Investigators also reported improvements in body weight, blood pressure, lipid levels and urinary albumin-to-creatinine ratio. Adverse events were mostly mild-to-moderate and GI-related, with no grade 3 hypoglycaemia events or evidence of liver toxicity.Hengrui plans to present the full HARBOR-1 and OUTSTAND-2 datasets at upcoming scientific meetings and submit regulatory applications for obesity and type 2 diabetes in China.Phase II global readout next yearThe readouts come as Kailera tests the drug outside of China. The company's ongoing placebo-controlled Phase II obesity trial in the US and Australia is evaluating a range of doses, including a lower starting dose of 15 mg, and a more gradual titration schedule in approximately 320 participants with obesity or overweight plus at least one co-morbidity. Results from that study are expected in 2027.Kailera had also licensed two other assets from Hengrui. The most advanced is ribupatide (KAI-9531/HRS-9531), a once-weekly injectable GLP-1/GIP dual agonist currently in a global Phase III programme for obesity, while KAI-4729 is a preclinical GLP-1/GIP/glucagon tri-agonist given as a once-weekly injectable.

Dive Brief:Kailera Therapeutics said its GLP-1 pill helped people with obesity in a short Phase 3 trial in China lose around one-tenth of their body weight, giving the newly public biotechnology firm another dataset in support of its plans to challenge marketed weight loss drugs from Eli Lilly and Novo Nordisk.At the highest daily dose tested, the drug, HRS-7535, helped enrollees lose an average of 9.8% of their body weight over 44 weeks, a finding that might make it a threat to Lillys Foundayo and Novos Wegovy pill. The drug also meaningfully dropped blood sugar in a separate late-stage test in diabetes. However, Kailera and its China-based partner, Hengrui Pharma, havent yet completed a Phase 2 trial in obesity in the kind of broader study population favored by the Food and Drug Administration.In April, Kailera completed one of the biggest-ever initial public offerings for a biotechnology company, selling $625 million in shares based on the strength of an obesity and metabolic-disease portfolio it licensed from Hengrui. Chief among those prospects is a dual-acting injection called ribupatide thats designed to have superior properties to Lillys Zepbound.Dive Insight:The market for obesity drugs is so vast that many companies believe theres enough room for several products as well as treatment strategies to thrive.Those looking for quick and significant weight loss, for instance, might turn to an injectable drug like Zepbound or the still-experimental retatrutide. In clinical testing, Zepbound helped people lose about a fifth of their body weight, on average, and retatrutide might be even more powerful.Oral medications, by comparison, offer the kind of convenience others might prefer. Though the approved treatments from Lilly and Novo arent as effective as their injectable counterparts, they give people an option that doesnt involve frequent shots.The Phase 3 trial results disclosed Tuesday suggested HRS-7535 could emerge as a new and comparable option, though Kailera and partner Hengrui will need to prove the drugs effectiveness in the sort of longer, global study Foundayo and the Wegovy pill have already completed. In clinical testing, the Wegovy pill helped people lose around 14% of their body weightafter 64 weeks. Foundayo was associated with roughly 11% weight lossafter 72 weeks.While HRS-7535 produced weight loss numbers that were numerically lower by comparison, thats not necessarily a surprise, as China-based trials tend to enroll people with a lower body-mass index as well as more men, wrote William Blair analyst Andy Hsieh.Hsieh expressed more concern with HRS-7535s safety, as testing showed that 70% of recipients had nausea and 67% to 69% reported vomiting, totals that alarmed his team.In our view, reducing the rate of nausea and vomiting to roughly mid-30% and mid-20%, respectively, will yield a competitive profile, Hsieh wrote. In an ongoing global Phase 2 trial, Kailera is starting with a lower dose and exploring a nighttime dosing cohort, he added.Hsieh did point out, however, that the trial revealed no signs of liver toxicity, a key concern with HRS-7535 because of structural similarities to Pfizers now-shelved obesity pill danuglipron. '