Patients in a phase 2b trial kept losing weight after switching to monthly dosing of Pfizer’s GLP-1 receptor agonist, providing early validation of the drugmaker’s $10 billion bet on Metsera.
The Vesper-3 trial randomized about 250 adults with obesity or who were overweight without Type 2 diabetes to receive one of four regimens of PF-08653944 or placebo. Everyone receiving PF’3944, previously known as MET-097i, started with 12 weekly doses before switching to a monthly regimen. The monthly doses were fourfold higher than the final weekly dose.
At Week 28, Pfizer reported placebo-adjusted weight loss of 10% and 12.3%, respectively, on the low and medium monthly maintenance dosing regimens the company plans to take into phase 3. Pfizer said there was robust and continuous weight loss after switching to monthly dosing and no plateau at Week 28. BMO Capital Markets analysts gave a cautious welcome to the data.
“On their face, the headline weight loss of 12.3% at 28 weeks look competitive, especially in the context of ongoing studies in combination with the company's amylin asset MET-233i,” the analysts said in a note to investors. “Still, we see some questions remaining around potential benefits from the placebo and study discontinuation rates into the full data.”
Before Pfizer closed its takeover, Metsera reported weight loss of up to 14.1% in a phase 2b trial of the weekly regimen. Guggenheim Securities said in a note to investors published before the weekly readout that competitors have reported 9% to 13% placebo-adjusted weight loss at Week 28, depending on the program and titration regimen used.
Pfizer’s monthly data fall into the range set by rivals, suggesting PF’3944 can provide competitive weight loss while freeing patients from the need to receive weekly injections. There is scope for Pfizer to drive deeper weight loss in phase 3. Having given monthly doses of up to 4.8 mg in Vesper-3, Pfizer plans to include a 9.6-mg cohort in its pivotal program.
In remarks prepared for Pfizer’s earnings call Tuesday, Chief Medical Officer Chris Boshoff, M.D., Ph.D., said (PDF) modeling predicts placebo-adjusted weight loss of nearly 16% at Week 28 on the high dose. Pfizer’s confidence in the model reflects the concordance between the expected and actual results for the two lower monthly maintenance doses.
“With these results, we are confident that ’3944 has the potential to deliver efficacy that is competitive with the standard of care, and potentially best-in-class among mono-agonists, with a differentiated monthly dosing format,” Boshoff said in the prepared remarks.
The plan to include a higher monthly maintenance dose in the phase 3 program is underpinned by safety and tolerability data, according to the company. Pfizer is yet to share detailed Week 28 safety and tolerability data from Vesper-3 but said gastrointestinal treatment-emergent adverse events were mostly mild or moderate. There was up to one instance of severe nausea or vomiting in any dose group, and no instances of severe diarrhea.
Ten patients in the low and medium monthly maintenance dosing cohorts stopped treatment because of adverse events. Discontinuations were evenly split between the weekly and monthly dosing periods. No patients stopped treatment because of adverse events in the placebo arm. The company plans to share full data from Vesper-3 in June.
Pfizer recently began a phase 3 trial of weekly PF’3944 and plans to start another nine phase 3 studies of the drug candidate this year. The roster includes trials of the weekly regimen in people with and without diabetes, an assessment of the monthly regimen and studies in a range of comorbidities.
In a note to clients Tuesday, Evercore ISI analyst Umer Raffat said that while the data are “very encouraging,” they may not have “accomplished all the objectives.” The analyst noted that in a prior data release, Metsera touted a higher placebo-adjusted weight loss result after a shorter trial period.
“Overall, while the development for this program is coming along, I think the data today may leave a bit more to be desired from a competitive perspective,” Raffat said, noting that results from Pfizer's GLP-1-amylin combo will be especially important in the wake of this readout.
Some Pfizer investors seemed to agree, as the company's share price slipped about 3.3% to $25.78 at 11:00 a.m. ET on Tuesday from a Monday closing price of $26.66.
The Big Pharma has launched the multifront push into obesity—which includes other Metsera assets and a GLP-1 small molecule licensed from Yao Pharma—to add growth drivers to offset its upcoming patent cliff. With multiple products losing patent protection in 2026 and 2027, Pfizer is racing to launch PF’3944 in 2028.
Editor's note: This story was updated at 11:00 a.m. ET to include analysis from Evercore ISI and the Pfizer stock reaction.