Pfizer Inc. (NYSE: PFE) today presented detailed results from multiple Phase 2b studies of berobenatide (PF'3944), an investigational, potential first-in-class monthly GLP-1 receptor agonist (GLP-1 RA) peptide, during a late-breaking expert symposium at the 86th Scientific Sessions of the American Diabetes Association (ADA).
The objectives for the Phase 2 studies were to identify the right doses for Phase 3 and to test escalation schemes. Across both weekly and monthly dosing in participants with obesity or overweight, with and without type 2 diabetes, the data from the Phase 2b VESPER-1, 2 and 3 studies:
- provide proof of concept for berobenatide as a potential first-in-class monthly GLP-1 RA peptide that can deliver competitive weight loss;
- show favorable tolerability for berobenatide, including low gastrointestinal (GI) adverse events and discontinuations despite rapid dose escalation and no allowed step-down; and
- highlight the potential for monthly delivery in a patient-friendly presentation with a very low 0.5 mL injection volume that provides convenience and scalability advantages.
The first clinical experience with the top weekly dose for berobenatide is being presented today for the first time. Results from a 32-week exploratory extension (Part B) of the Phase 2b VESPER-1 study showed a non-placebo-adjusted weight loss of 15.9%* with no plateau observed at 32 weeks on berobenatide (Week 60 of the overall study), in participants who escalated from placebo to 2.4 mg weekly berobenatide. VESPER-1 is evaluating once-weekly berobenatide in adults with obesity or overweight, including Part B to assess the durability of weight loss and the impact of transitioning from once-weekly to less frequent dosing regimens, 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."
Detailed results from the previously reported Phase 2b VESPER-3 study are also being presented today, which is evaluating monthly maintenance dosing of berobenatide in adults with obesity or overweight without type 2 diabetes. In addition, data from the Phase 2b VESPER-2 study, which evaluated weekly dosing of berobenatide in adults with obesity or overweight and type 2 diabetes, showed dose dependent reductions from baseline were observed with berobenatide for both body weight and HbA1c. Of note, there was a 2.2%** reduction in HbA1c achieved with berobenatide 1.6 mg weekly at week 28 (on treatment [efficacy] estimand), compared to a reduction of 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."
The VESPER-6 pivotal Phase 3 study investigating monthly maintenance dosing for berobenatide in adults with obesity or overweight is open for enrollment, as well as the SOLIS-1 Phase 2b study investigating weekly and monthly maintenance dosing of an ultra-long-acting amylin analog (PF'3945) as a monotherapy and in combination with berobenatide.
An investor slide presentation with more information about the VESPER clinical development program and the clinical trial results contained in this release will be available on Pfizer's web site at 10:00 a.m. CT / 11:00 a.m. ET at www.pfizer.com/investors.
About Berobenatide and Pfizer's Cardiometabolic Pipeline
Pfizer plans to advance 20+ trials for obesity and related comorbidities in 2026. This includes 10 ongoing and planned Phase 3 trials for berobenatide (PF'3944), an investigational, potential first-in-class monthly GLP-1 receptor agonist (GLP-1 RA) peptide being studied for chronic weight management and obesity-related comorbidities including knee osteoarthritis and obstructive sleep apnea. The growing body of evidence supports advancing an extensive development program for berobenatide as a monotherapy and in combination with various Nutrient-Stimulated Hormone (NuSH) peptides including amylin analogs.
About the VESPER Clinical Development Program
The VESPER clinical development program is a comprehensive global program evaluating berobenatide across a range of patient populations and dosing regimens in chronic weight management.
Phase 2b VESPER studies include:
- VESPER-1: A Phase 2b trial in adults with obesity or overweight evaluating once-weekly berobenatide, including a 32-week exploratory extension (Part B) assessing the durability of weight loss and the impact of transitioning from once-weekly to less frequent dosing regimens, including once-monthly administration. Part A was the initial 28-week double-blind placebo-controlled portion of the study.
- VESPER-2: A Phase 2b randomized, double-blind, placebo-controlled trial evaluating once- weekly berobenatide in adults with obesity or overweight and type 2 diabetes, designed to assess weight loss, glycemic control and safety in this population.
- VESPER-3 is an ongoing 64-week, randomized, double-blind, placebo-controlled study in participants with obesity or overweight without type 2 diabetes. The study is designed to evaluate weekly (QW) titration phase to monthly (QM) dosing of berobenatide in four different titration and QM dose arms, compared to placebo.
Phase 3 VESPER studies include:
- VESPER-4 is an ongoing Phase 3 pivotal study investigating once-weekly berobenatide in adults with obesity or overweight and without type 2 diabetes.
- VESPER-5 is an ongoing Phase 3 pivotal study investigating once-weekly berobenatide in adults with obesity or overweight and type 2 diabetes. A higher weekly dose of berobenatide (2.4 mg) is currently being evaluated in Phase 3.
- VESPER-6 is a Phase 3 pivotal study investigating once-monthly berobenatide in adults with obesity or overweight. The study is now open for enrollment.
- Seven additional planned Phase 3 studies of berobenatide are designed to target comorbidities and increase patient optionality and access.
About Obesity
Obesity is a growing global epidemic. In 2015, it was estimated that approximately 1.9 billioni people were living with obesity or considered overweight, and this number is expected to grow to more than 2.9 billion by 2030.ii Obesity is a complex metabolic disease, often defined in adults as having a body mass index (BMI) greater than or equal to 30.iii It is associated with more than 200 health conditions,iv contributing to significant chronic disease burden, shortened lifespans, and growing healthcare costs. Despite recent advances in care, for many patients, current therapies are not sufficient-whether due to limited efficacy, tolerability issues that impact adherence, co-morbidities that weight loss alone doesn't address, or barriers to access and affordability. New waves of innovation that better meet the diverse needs of patients are critical to effectively address this epidemic.
