Pfizer (NYSE:PFE) announced positive topline results from the Phase 2b VESPER-3 study evaluating monthly maintenance dosing of its fully-biased, ultra-long-acting injectable GLP-1 receptor agonist PF’3944 (nexiguran ziclumeran) in adults with obesity or overweight without type 2 diabetes.
The study met both primary objectives: demonstrating continued weight loss after switching from weekly to monthly subcutaneous injections (four-fold reduction in dosing frequency) and maintaining efficacy while preserving a well-tolerated safety profile.
At week 28, placebo-adjusted weight loss reached up to 12.3% (efficacy estimand), with the primary endpoint of weight reduction from randomization to week 28 showing statistical superiority to placebo across all four dose regimens tested (P < 0.001).
No plateau in weight loss was observed at week 28, suggesting potential for further reductions through the ongoing 64-week study.
The trial included up to two titration steps with weekly dosing through week 12, followed by monthly dosing to week 28.
The low (3.2 mg) and medium (4.8 mg) monthly maintenance regimens planned for Phase 3 achieved 10% and 12.3% placebo-adjusted weight loss, respectively.
Gastrointestinal treatment-emergent adverse events were predominantly mild or moderate, with no more than one instance of severe nausea or vomiting in any dose group and no severe diarrhea.
Discontinuations due to adverse events were low and balanced between treatment and placebo arms.
Jim List, MD, PhD, Chief Internal Medicine Officer at Pfizer, stated: “These topline results from the Phase 2b VESPER-3 study reinforce the potential of PF’3944 as a monthly treatment with competitive efficacy. Based on the monthly dosing efficacy and tolerability demonstrated in this trial, we remain confident in our plan to include a higher 9.6 mg monthly maintenance dose of PF’3944 in Phase 3.”
Following the recent acquisition of Metsera and an exclusive global collaboration and license agreement with YaoPharma, Pfizer now has a diversified obesity pipeline encompassing injectable and oral GLP-1 receptor agonists, GIPR agonists and antagonists, and amylin analogs.
The company plans an expansive development program with more than 20 trials in 2026, including 10 Phase 3 studies of PF’3944 targeting obesity, overweight, type 2 diabetes, and comorbidities to expand patient optionality and access.
Detailed results from VESPER-3 will be presented on June 6, 2026, at the 86th Scientific Sessions of the American Diabetes Association.
The ongoing 64-week study continues to evaluate long-term efficacy and safety.