Genentech Reports Positive Phase II Results for Petrelintide, an Amylin Analog for Overweight and Obesity
Genentech, a member of the Roche Group today announced positive topline results from the Phase II ZUPREME-1 trial evaluating the investigational drug petrelintide versus placebo in adults living with overweight and obesity. The trial enrolled 493 participants with a mean body mass index (BMI) of 37 kg/m² and a well-balanced gender distribution.
The study met its primary endpoint, demonstrating that once-weekly subcutaneous injections of petrelintide—with dose escalation every four weeks—resulted in statistically significant and clinically meaningful weight loss after 28 weeks compared to placebo. Participants across all five treatment arms achieved sustained weight reduction through week 42, with the highest efficacy cohort reaching an average of 10.7% weight loss from baseline, versus 1.7% for the placebo group. In this same cohort, 98% of participants achieved the maintenance dose, underscoring the favorable tolerability of the treatment. Body weight reduction measured by the treatment regimen estimand aligned closely with the efficacy estimand, and notably, female participants lost substantially more weight than male participants during the trial.
“Petrelintide achieved meaningful weight loss with a well-tolerated dosing approach, which is essential to support long-term and sustained benefits in people living with obesity,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. “These data reinforce our confidence in petrelintide’s potential to address important unmet medical needs in chronic weight management.”
Petrelintide demonstrated a favorable safety and tolerability profile comparable to placebo, with no unexpected safety signals observed. Discontinuation due to adverse events (AEs) was 4.8% in the maximally effective treatment arm versus 4.9% for placebo. The most commonly reported AEs were gastrointestinal in nature, the majority of which were mild. Interestingly, the proportion of participants experiencing vomiting was lower than in the placebo group, and no vomiting occurred in the maximally effective treatment arm. Rates of diarrhea and constipation were consistent with placebo and remained in the single-digit range. Nausea, which had been more common in the prior 16-week Phase 1b trial using a faster dose escalation schedule, was less frequent in ZUPREME-1, with almost no cases reported after reaching the maintenance dose. Overall trial withdrawal was 8.4% across petrelintide arms, compared with 13.6% in the placebo group.
The final ZUPREME-1 dataset, including a nine-week safety follow-up, will be presented at an upcoming medical congress and will guide the design of Phase III trials. Topline results from a second Phase II petrelintide monotherapy trial, ZUPREME-2—evaluating the drug in people living with overweight or obesity and type 2 diabetes—are expected in the second half of 2026. In addition, a Phase II trial exploring the combination of petrelintide with CT-388 is planned for later in 2026.
With a growing cardiometabolic portfolio and strong diagnostic expertise, Genentech continues to advance treatments to address the diverse needs of people living with obesity and related comorbidities. Obesity is recognized globally as the greatest single risk factor for chronic disease. By 2035, over four billion people—more than half the world’s population—are projected to be living with overweight or obesity. This trend, driven by genetics, biology, behavior, environment, and socioeconomic factors, is placing a significant burden on healthcare systems due to associated comorbidities and reduced quality of life.
In 2025, Genentech and Roche entered an exclusive collaboration with Zealand Pharma to co-develop and co-commercialize petrelintide for people living with overweight and obesity.
About ZUPREME-1 [NCT06662539]
ZUPREME-1 is a 42-week randomized, double-blind, placebo-controlled, dose-finding Phase II trial including 493 participants with a mean baseline weight of 107 kg, a mean BMI of 37 kg/m², and a mean age of 48 years. The trial population was 53% female, allowing for balanced gender representation and comprehensive data collection. The study compared five doses of once-weekly petrelintide versus placebo, alongside a reduced-calorie diet and increased physical activity, in participants with obesity or overweight with weight-related comorbidities.
The trial included a screening period, a 16-week dose escalation period with four-week dose increments, a maintenance period through week 42, and a nine-week follow-up period ending at week 51. ZUPREME-1 enrolled participants across 33 sites in the United States, Poland, and Romania. The primary endpoint was the percentage change in body weight from baseline to week 28. Secondary endpoints included percentage change in body weight through week 42, changes in waist circumference, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hsCRP), fasting lipids, fasting glucose, and exploratory endpoints including body composition changes measured via MRI.
About Petrelintide
Petrelintide is an investigational long-acting amylin analog designed for once-weekly subcutaneous administration. Its chemical and physical stability allows co-formulation and co-administration with other peptides. Amylin is a hormone produced by pancreatic beta cells and co-secreted with insulin in response to meals. Activation of amylin receptors reduces body weight by enhancing sensitivity to the satiety hormone leptin, promoting earlier fullness and supporting weight reduction. Petrelintide’s mechanism and favorable tolerability profile make it a promising therapeutic candidate for chronic weight management.
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