Roche Reports Positive Phase II Results for Investigational Obesity Drug Petrelintide

Roche has announced positive topline results from the Phase II ZUPREME-1 trial, evaluating the investigational obesity therapy petrelintide.

The study showed that once-weekly injections of petrelintide produced significant and clinically meaningful weight loss compared with placebo in people living with overweight or obesity.

The results strengthen Roche’s growing presence in the cardiometabolic and obesity treatment market, one of the fastest-growing areas in global pharma.

Key Results From the ZUPREME-1 Trial

The ZUPREME-1 study included 493 participants with overweight or obesity, with an average BMI of 37 kg/m². After 28 weeks of treatment, petrelintide met the trial’s primary endpoint.

Major findings include:

• Statistically significant weight loss across all five petrelintide treatment arms versus placebo
• Up to 10.7% mean weight loss at week 42 using the efficacy estimand
• 1.7% weight loss with placebo
• 98% of participants in the highest-performing cohort reached the maintenance dose
• Greater weight loss observed in female participants compared with males

These findings suggest that petrelintide may offer a well-tolerated and effective option for long-term weight management.

Safety and Tolerability Profile

Petrelintide demonstrated a favourable safety profile in the trial.

Key safety observations included:

• No unexpected safety signals
• 4.8% treatment discontinuation due to adverse events, compared with 4.9% for placebo
• Most side effects were mild gastrointestinal events

Other notable observations:

• Vomiting occurred less frequently than with placebo
• No vomiting was reported in the most effective treatment arm
• Rates of diarrhoea and constipation remained low
• Nausea rates were lower than in the earlier Phase 1b trial

Trial withdrawal for any reason was 8.4% for petrelintide, compared with 13.6% for placebo.

What Comes Next for Petrelintide?

The full ZUPREME-1 dataset, including a nine-week safety follow-up, will be presented at an upcoming medical congress. The results will help determine the design of future Phase III trials.

Several additional studies are already planned:

• ZUPREME-2 Phase II trial, evaluating petrelintide in people with obesity and type 2 diabetes (results expected in H2 2026)
• A Phase II combination trial of petrelintide with CT-388, expected to begin in 2026

In 2025, Roche also entered an exclusive collaboration with Zealand Pharma to co-develop and commercialize petrelintide for obesity and overweight treatment.

Inside the ZUPREME-1 Study Design

The ZUPREME-1 trial was a 42-week randomized, double-blind, placebo-controlled Phase II study.

Important study characteristics include:

• 493 participants
• Mean body weight: 107 kg
• Mean BMI: 37 kg/m²
• Mean age: 48 years
• 53% female participants

The trial tested five doses of once-weekly petrelintide injections alongside lifestyle interventions such as:

• Reduced-calorie diet
• Increased physical activity

Participants were enrolled across 33 clinical sites in the United States, Poland, and Romania.

Primary endpoint:

• Percentage change in body weight from baseline to week 28

Secondary endpoints included:

• Body weight change at week 42
• Waist circumference
• HbA1c levels
• Fasting glucose and lipid levels
• High-sensitivity C-reactive protein (hsCRP)

How Petrelintide Works?

Petrelintide is an investigational long-acting amylin analogue designed for once-weekly subcutaneous administration. Amylin is a hormone produced in pancreatic beta cells and released alongside insulin after food intake.

Activation of the amylin receptor can:

• Increase feelings of fullness
• Restore sensitivity to the satiety hormone leptin
• Reduce food intake and body weight

Petrelintide has been engineered for chemical stability at neutral pH, which may enable co-formulation with other peptide therapies in the future.

The Growing Global Obesity Challenge

Obesity continues to represent a major global health challenge. Key projections include:

• By 2035, more than 4 billion people worldwide could be living with overweight or obesity
• The condition is a major risk factor for cardiovascular disease, diabetes, and other chronic conditions

As healthcare systems face increasing pressure, pharmaceutical companies are accelerating innovation in next-generation obesity therapies.

About Roche

Founded in 1896 in Basel, Switzerland, Roche has grown into:

• The world’s largest biotechnology company
• A global leader in in-vitro diagnostics

The company focuses on developing innovative medicines and diagnostics aimed at improving and saving lives across a wide range of diseases.

With the advancement of petrelintide and other cardiometabolic therapies, Roche is expanding its strategy to address obesity and its related health complications.

Bottom line:

Roche’s Phase II results suggest that petrelintide could become a promising new therapy in the rapidly evolving obesity treatment landscape, with strong weight-loss outcomes and a favourable tolerability profile as the drug moves toward Phase III development.

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