Pfizer Inc. has announced positive topline results from its phase 2b VESPER-3 study investigating monthly maintenance dosing of its fully-biased, ultra-long-acting, injectable GLP-1 receptor agonist (RA) PF’3944 (MET-097i) in adults with obesity or overweight without type 2 diabetes.
The study was looking to show PF’3944 could achieve continued weight loss when switching from weekly to monthly subcutaneous injections and maintain its efficacy while reducing the dosing frequency four-fold; and to demonstrate it could switch to a four-fold equivalent monthly dose while maintaining a well-tolerated and favourable safety profile.
At week 28, 10% and 12.3% placebo-adjusted weight loss was achieved in Arms 1 and 3 respectively, which are the low and medium monthly maintenance dosing regimens planned for inclusion in phase 3. The data show robust and continuous weight loss after switching to monthly dosing, with no plateau observed at week 28, suggesting continued weight loss is expected as the study continues through week 64.
PF’3944 also maintained a well-tolerated and favourable safety profile through week 28 consistent with the GLP-1 RA class. Observed gastrointestinal treatment-emergent adverse events (TEAEs) were predominantly mild or moderate with no more than one instance of severe nausea or vomiting observed in any dose group, and no instances of severe diarrhoea. Across Arms 1 and 3, five total participants discontinued from treatment due to adverse events (AEs) in the weekly phase and five total participants discontinued from treatment due to AEs in the monthly phase. There were zero discontinuations from treatment due to AEs in the placebo group.
The study demonstrated statistically significant weight reduction with up to 12.3% mean placebo-adjusted weight loss at week 28. The study included up to two titration steps and weekly dosing with PF’3944 until week 12, followed by monthly dosing to week 28. The primary endpoint of weight reduction from randomization to week 28 was superior to placebo in all four dose regimens tested. The detailed results will be presented in June at the 86th Scientific Sessions of the American Diabetes Association.
“These topline results from the phase 2b VESPER-3 study reinforce the potential of PF’3944 as a monthly treatment with competitive efficacy,” said Jim List, chief internal medicine officer.
“Based on the monthly dosing efficacy and tolerability demonstrated in this trial, we remain confident in our plan to include a higher 9.6mg monthly maintenance dose of PF’3944 in phase 3. With PF’3944 as an anchor of Pfizer’s obesity pipeline, we are positioned to address critical gaps in obesity care and meet the diverse needs of patients.”
Following its recent acquisition of Metsera and exclusive global collaboration and license agreement with YaoPharma, Pfizer now has a diverse pipeline of clinical stage injectable and oral obesity candidates targeting GLP-1 receptor as well as glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists and antagonists, and amylin analogues.
Pfizer is planning an expansive obesity development program across its pipeline, with plans to advance more than 20 trials in 2026. This includes 10 phase 3 trials of PF’3944.