Pfizer's Monthly GLP-1 Shot PF'3944 Meets Goal in Phase 2b VESPER-3 Obesity Trial
The former Metsera drug produced up to 12.3% placebo-adjusted weight loss at 28 weeks after a switch from weekly to monthly injections, Pfizer reported, and the company plans 10 Phase 3 trials this year.
These results come from a Phase 2 trial, which tests whether a treatment works and refines the dose.
Key points
- All four PF’3944 dose regimens beat placebo on weight reduction at week 28 in the Phase 2b VESPER-3 study, Pfizer reported in topline results.
- The two monthly maintenance regimens planned for Phase 3 produced 10% and 12.3% placebo-adjusted weight loss, with no plateau seen at week 28, the company said.
- Pfizer expects 10 Phase 3 trials of PF’3944 to advance in 2026 and will present detailed VESPER-3 data at the American Diabetes Association meeting in June.
Pfizer said on February 3 that its monthly injectable obesity candidate PF-08653944, known as PF’3944 and previously as MET-097i, met the primary endpoint of the Phase 2b VESPER-3 study, producing up to 12.3% mean placebo-adjusted weight loss at 28 weeks in adults with obesity or overweight who do not have type 2 diabetes, according to the company's topline release.
The drug is an ultra-long-acting GLP-1 receptor agonist that Pfizer gained through its acquisition of Metsera. The results are company-reported topline data; Pfizer said the detailed results will be presented on June 6 at the American Diabetes Association's 86th Scientific Sessions.
Weekly start, monthly maintenance
VESPER-3 is an ongoing 64-week, randomized, double-blind, placebo-controlled study with five arms of about 54 participants each. Participants took PF’3944 weekly through up to two titration steps until week 12 and then switched to monthly injections through week 28. The study was designed to show that weight loss would continue after that switch, cutting dosing frequency four-fold, and that the monthly dose would remain well tolerated.
Weight reduction from randomization to week 28 was superior to placebo in all four dose regimens tested (P < 0.001), Pfizer said. The two arms that use the low and medium monthly maintenance doses planned for Phase 3 produced placebo-adjusted weight loss of 10% and 12.3%. Those figures exclude data after protocol-defined events such as stopping treatment; counting all available weight measurements regardless of adherence, the figures were 8.4% and 10.5%.
Pfizer said weight loss continued after the switch to monthly dosing, with no plateau observed at week 28, and that it expects further weight loss as the study runs to week 64.
Tolerability and Phase 3 plans
Gastrointestinal side effects were mostly mild or moderate, the company said, with no more than one case of severe nausea or vomiting in any dose group and no severe diarrhea. Across the two arms planned for Phase 3, five participants stopped treatment because of adverse events during the weekly phase and five during the monthly phase. No one in the placebo group stopped for that reason.
"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," Jim List, Pfizer's chief internal medicine officer, said in the release, as quoted by HCPLive.
Pfizer said it expects 10 Phase 3 trials of PF’3944 to advance in 2026, part of more than 20 planned and ongoing obesity studies. They include the Phase 3 VESPER-4 study of once-weekly dosing in people without type 2 diabetes, which has already started; the planned VESPER-5 study of weekly dosing in people with type 2 diabetes; and the planned VESPER-6 study of once-monthly dosing. The company is also testing PF’3944 in combination with an amylin analog and a GIPR agonist from the Metsera pipeline.
HCPLive reported that VESPER-3 enrolled adults with a body mass index of 30 to 50, or 27 to under 30 with at least one weight-related condition such as hypertension or dyslipidemia, and excluded people with diabetes.