Global Registrational Phase 3 ZUPREME Program Evaluating Petrelintide in Overweight or Obesity Initiated – Zealand Pharma

Zealand Pharma A/S announces the initiation of the global registrational Phase 3 Zupreme program, evaluating the efficacy and safety of once-weekly petrelintide versus placebo in people with overweight or obesity.

The Phase 3a program for petrelintide monotherapy, which is being conducted with Zealand Pharma’s partner Roche, consists of three trials: Zupreme-3, Zupreme-4, and Zupreme-5, evaluating the efficacy and safety of once-weekly petrelintide versus placebo in people with obesity or overweight without type 2 diabetes, people with obesity or overweight with type 2 diabetes, and people with obesity or overweight and established cardiovascular disease, respectively. The three trials are expected to enroll approximately 7,000 participants in total.

“The Phase 3a program is designed to confirm the first-choice potential of petrelintide – supported by the data we have seen throughout the clinical trials with petrelintide: clinically meaningful double-digit weight reduction and a tolerability profile that supports the long-term adherence that chronic weight management requires.” – David Kendall, MD, Chief Medical Officer at Zealand Pharma.

“The program is designed to generate the robust, longer-term evidence needed to support regulatory filings and bring petrelintide to the millions of people demanding a better weight management experience.” – David Kendall, MD, Chief Medical Officer at Zealand Pharma.

About the Phase 3a Zupreme program

Zupreme-3 is a randomized, double-blind, placebo-controlled, Phase 3 trial, evaluating the efficacy and safety of once-weekly petrelintide compared with placebo in participants living with overweight (BMI ≥ 27 < 30 kg/m2) or obesity (BMI ≥ 30 kg/m2) with at least one weight-related comorbidity without type 2 diabetes (T2D). The trial will enroll a total of approximately 3,900 participants.

Zupreme-4 is a randomized, double-blind, placebo-controlled, Phase 3 trial, evaluating the efficacy and safety of once-weekly petrelintide compared with placebo in participants living with overweight or obesity and T2D. The trial will enroll a total of approximately 600 participants.

The Zupreme-3 and Zupreme-4 trials include a screening period, a dose escalation period of 12 weeks followed by a maintenance period until week 64, and a safety follow-up period after treatment is completed until week 77. All participants who complete the week 64 visit will be eligible to continue in an optional open-label extension (OLE) study. Participants in the OLE study will be offered treatment with petrelintide regardless of which treatment arm they were allocated in the main study.

Zupreme-5 is a randomized, double-blind, placebo-controlled, Phase 3 trial, evaluating the efficacy and safety of once-weekly petrelintide in participants living with overweight or obesity and established cardiovascular disease (CVD) with or without T2D. Zupreme-5 includes a screening period, a dose escalation period of 12 weeks followed by a maintenance period, with the primary efficacy assessment occurring at week 64. Following the primary assessment, participants continue into an event-maintenance phase. The trial can last up to a total of 3 years and will enroll a total of approximately 2,500 participants.

The primary endpoint in the Phase 3 Zupreme trials is percentage change in body weight from baseline to week 64. Secondary endpoints include, but are not limited to, change in waist circumference, HbA1c, cardiometabolic risk factors, physical functioning, and change in eating behaviors.