Phase 2b data backs monthly dosing potential for Pfizer’s GLP-1 RA berobenatide with strong efficacy and tolerability findings

Detailed findings from several Phase 2b investigations of berobenatide (PF’3944), an investigational potential first-in-class monthly GLP-1 receptor agonist (GLP-1 RA) peptide, were shared during a late-breaking expert symposium at the 86th Scientific Sessions of the American Diabetes Association (ADA). The Phase 2 work was designed to pinpoint the right doses for Phase 3 and to assess escalation approaches. Spanning both weekly and monthly dosing in participants living with obesity or overweight, with and without type 2 diabetes, the collective evidence from the VESPER-1, 2, and 3 Phase 2b studies:

• establishes proof of concept for berobenatide as a potential first-in-class monthly GLP-1 RA peptide capable of delivering competitive weight loss
• points to a favourable tolerability profile, with low rates of gastrointestinal adverse events and discontinuations even under rapid dose escalation with no step-down option permitted
• underscores the appeal of monthly delivery in a patient-friendly format, with a 0.5 mL injection volume that brings convenience and scalability benefits

The first clinical data at the highest weekly dose for berobenatide were unveiled for the first time. Coming from a 32-week exploratory extension of the Phase 2b VESPER-1 study, the results captured a non-placebo-adjusted weight loss of 15.9% with no sign of plateau at 32 weeks among participants who had transitioned from placebo to 2.4 mg weekly berobenatide. VESPER-1 is examining once-weekly berobenatide in adults with obesity or overweight, with the extension arm looking at the durability of weight loss and the effects of moving from weekly to less frequent dosing, including once-monthly.

“In Phase 2b studies, berobenatide delivered continuous, uninterrupted weight loss at all doses selected for Phase 3, while preserving a tolerable profile as people transitioned from a weekly to a monthly maintenance dose,” said Jim List, MD, PhD, Chief Internal Medicine Officer, Pfizer. “These data highlight the potential for berobenatide to be the first approved monthly GLP-1 RA peptide and support our extensive Phase 3 program that includes 10 studies for chronic weight management and obesity-related comorbidities. With berobenatide as a potential foundational metabolic medicine, both as a single agent and as a combination backbone, Pfizer is advancing a differentiated pipeline with multiple mechanisms and modalities designed to meet the many needs of people living with obesity and related conditions.”

Further findings from the previously reported Phase 2b VESPER-3 study, which is examining monthly maintenance dosing of berobenatide in adults with obesity or overweight without type 2 diabetes, were also presented. Separately, data from the Phase 2b VESPER-2 study, which looked at weekly berobenatide dosing in adults with obesity or overweight alongside type 2 diabetes, showed dose-dependent reductions from baseline in both body weight and HbA1c. At week 28, those on berobenatide 1.6 mg weekly recorded an HbA1c reduction of 2.2%, against just 0.2% in the placebo group.

“Weight management is a lifelong commitment, and the barriers to staying on therapy long-term are just as important as the therapy itself,” said John B. Buse, MD, PhD, Professor of Medicine at the University of North Carolina School of Medicine, Chapel Hill. “The growing body of evidence shows berobenatide delivering meaningful weight loss with a well-tolerated profile following a switch from weekly to monthly dosing in Phase 2b studies. If approved, berobenatide has the potential to not only be effective, but practical and sustainable in real life.”

Enrolment is now open for the VESPER-6 pivotal Phase 3 study, which is assessing monthly maintenance dosing of berobenatide in adults living with obesity or overweight. The SOLIS-1 Phase 2b study is also underway, investigating weekly and monthly maintenance dosing of an ultra-long-acting amylin analog (PF’3945) both as a standalone therapy and in combination with berobenatide.

Pfizer’s broader obesity ambitions include more than 20 trials planned for 2026 targeting obesity and related conditions. Among these are 10 ongoing and planned Phase 3 trials for berobenatide, covering chronic weight management and obesity-related complications such as knee osteoarthritis and obstructive sleep apnea. The accumulating evidence is lending further support to an extensive development programme for berobenatide, both on its own and paired with various Nutrient-Stimulated Hormone (NuSH) peptides including amylin analogs.

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GLP-1, Pfizer, Pfizer's GLP-1 RA berobenatide, Phase 2 trial, Phase 2b data