First patients randomised in KaiNETIC Global Phase 3 Clinical Program of ribupatide

Kailera Therapeutics has announced the randomisation of the first participants in the KaiNETIC global Phase 3 clinical program of ribupatide (also known as KAI-9531), an investigational once-weekly injectable dual GLP-1/GIP receptor agonist peptide, for the treatment of people living with obesity or overweight.

The KaiNETIC global Phase 3 clinical program includes three global, double-blind, randomized, placebo-controlled Phase 3 trials (KaiNETIC-1, KaiNETIC-2, and KaiNETIC-3) to evaluate weekly ribupatide doses of up to 10 mg administered by subcutaneous injection over 76 weeks:

• KaiNETIC-1: target enrolment of 1,800 adults with a BMI of 30 kg/m2 or greater, or a BMI of 27 kg/m2 or greater with a comorbidity, excluding type 2 diabetes

• KaiNETIC-2: target enrolment of 1,700 adults with a BMI of 27 kg/m2 or greater with type 2 diabetes

• KaiNETIC-3: target enrolment of 1,200 adults with a BMI of 35 kg/m2 or greater and without type 2 diabetes. This trial will include an arm that will be randomised to open-label semaglutide 2.4 mg subcutaneous weekly injection.

KaiNETIC is a global Phase 3 program consisting of three double-blind, randomized, placebo-controlled Phase 3 clinical trials designed to evaluate the efficacy and safety of ribupatide for the treatment of obesity or overweight. The trial will evaluate ribupatide doses up to 10 mg administered by weekly subcutaneous injection over a period of 76 weeks with dose titration for up to 24 weeks and a maintenance dose of at least 52 weeks. The trials will enroll participants in North America, Europe, UK, Oceania, and South America.

The first trial, KaiNETIC-1, targets enrollment of approximately 1,800 participants with a BMI of 30 kg/m2 or greater or a BMI of 27 kg/m2 or greater with a comorbidity, excluding type 2 diabetes. The primary endpoint of the trial is the percentage change in body weight from baseline at Week 76. The second trial, KaiNETIC-2, targets enrollment of approximately 1,700 participants with a BMI of 27 kg/m2 or greater and type 2 diabetes. The co-primary endpoints of this trial are percentage change in body weight from baseline and change in hemoglobin A1c from baseline at Week 76.

In KaiNETIC-1 and KaiNETIC-2, participants will be randomized to a ribupatide dose of 4 mg, 6 mg, 8 mg, and 10 mg, or placebo. Both trials will also evaluate ribupatide in a pre-defined subgroup of participants with BMI 35 kg/m2 or greater.

The third trial, KaiNETIC-3, targets enrolment of approximately 1,200 adults with a BMI of 35 kg/m2 or greater and without type 2 diabetes. Participants will be randomized to ribupatide doses of 8 mg or 10 mg, placebo, or open-label semaglutide 2.4 mg. The co-primary endpoints of this trial are percentage change in body weight from baseline compared to placebo at Week 76 and percentage change in body weight from baseline compared to semaglutide 2.4 mg at Week 76.

Ribupatide (also known as KAI-9531 and being developed as HRS9531 by Hengrui Pharma in Greater China) is a once-weekly injectable GLP-1 (glucagon-like peptide-1)/GIP (glucose-dependent insulinotropic polypeptide) receptor dual agonist peptide. Over 2,500 clinical trial participants have been dosed with ribupatide with treatment out to 52 weeks, including in multiple late-stage clinical trials conducted by Hengrui in China. Hengrui submitted a marketing authorization application to the National Medical Products Administration (NMPA) in China for long-term weight management of HRS9531 in adults. Ribupatide is currently being evaluated in the KaiNETIC global Phase 3 clinical program comprised of three Phase 3 trials.

In a previously reported clinical trial conducted by Hengrui in China, after 36 weeks, including only 12 weeks of treatment at the 8 mg dose, ribupatide reduced body weight by 23.6% from baseline, compared to a 1.8% reduction with placebo, based on the efficacy estimand, with no observed plateau in weight loss and a favorable safety profile consistent with other GLP-1-based treatments.