On February 3, Pfizer (PFE.US) announced positive topline results from the Phase 2b VESPER-3 study for its ultra-long-acting injectable GLP-1 receptor agonist (RA), PF-3944 (MET-097i).

The study evaluated a once-monthly maintenance dosing regimen in adult patients with obesity or overweight without type 2 diabetes.

PF-3944 is an ultra-long-acting, fully biased GLP-1 receptor agonist acquired by Pfizer through its recent purchase of Metsera, possessing the potential for once-monthly injection.

It is currently being developed as a once-weekly (QW) monotherapy and a monthly regimen, with exploration for use in combination with various peptide-based agents, including the amylin analog PF-08653945 (PF-3945; MET-233i) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist PF-08654696 (MET-034i).

Results showed that at week 28, patients in Group 1 and Group 3 achieved weight reductions of 10% and 12.3%, respectively, compared to the placebo group.

These data indicate that after switching to a once-monthly dosing schedule, weight loss was robust and sustained, with no plateau observed by week 28, and further reductions are projected to continue through week 64.

Through week 28, PF-3944 also maintained a favorable and acceptable safety profile consistent with the GLP-1 RA class.

The observed gastrointestinal treatment-emergent adverse events (TEAEs) were predominantly mild or moderate in severity, with only one case of severe nausea or vomiting across all dose groups and no instances of severe diarrhea.

In Groups 1 and 3, five patients discontinued treatment due to adverse events (AEs) during the weekly phase, and five patients discontinued due to AEs during the monthly phase.

No treatment discontinuations due to AEs occurred in the placebo group.

Following the recent acquisition of Metsera and a global exclusive collaboration and license agreement with YaoPharma, Pfizer has now established a diverse clinical-stage pipeline of obesity candidates.

This pipeline encompasses injectable and oral therapies targeting the GLP-1 receptor, GIPR agonists and antagonists, and amylin analogs.

Pfizer plans to advance a large-scale obesity development program, anticipating the initiation of over 20 clinical trials by 2026.

This includes 10 Phase 3 studies for PF-3944: the already-initiated pivotal Phase 3 VESPER-4 study evaluating once-weekly PF-3944 in people with obesity or overweight without type 2 diabetes; the planned Phase 3 VESPER-5 study evaluating once-weekly PF-3944 in people with obesity or overweight and type 2 diabetes; the planned Phase 3 VESPER-6 study evaluating once-monthly PF-3944 in people with obesity or overweight; and at least seven other planned Phase 3 studies aimed at covering comorbidities and enhancing patient treatment options and accessibility.