Patients who switched from weekly to monthly maintenance dosing of an experimental Pfizer obesity drug achieved an average placebo-adjusted weight loss of up to 12.3% in a mid-stage study, results that help build the case for offering patients less frequent injections of this GLP-1 medication.
The Phase 2b study has two main goals: showing the study drug, PF-08653944, can achieve weight loss and maintain efficacy when patients switch to monthly dosing, and demonstrating that the switch to a four-fold equivalent monthly dose maintains favorable tolerability and safety.
Four doses of the drug, PF-08653944, were evaluated in the 64-week study, which enrolled participants with obesity or overweight without type 2 diabetes. The trial was designed with two titration steps and weekly dosing until week 12, followed by monthly maintenance dosing. In preliminary results reported Tuesday, Pfizer said weight reduction for all four doses was superior to placebo at week 28. There was no plateau observed at this point, suggesting patients will continue to lose weight as the study continues through 64 weeks.
MedCity News Pivot Podcast: How Emergency Departments Are Using Real-Time Data to Improve Outcomes
How can AI benefit and improve patient outcome in the emergency department? Watch the latest episode to find out.
Even within the context of preliminary results, there’s limited data to parse. Pfizer only reported results for two of the four arms of PF’3944’s study, the low- and medium-monthly dosing regimens. The company said these are the doses planned for inclusion in Phase 3 testing. The 12.3% placebo-adjusted weight loss reported at 28 weeks was for the 4.8 mg medium dose; the 3.2 mg low-dose group showed a 10% placebo-adjusted weight loss.
As for the gastrointestinal problems that are a class-wide effect and lead many patients to stop taking GLP-1 drugs, Pfizer said these events were mild or moderate. No more than one instance of severe nausea or vomiting was observed in any dose group and there were no instances of severe diarrhea. Pfizer said detailed results will be presented in June during the scientific sessions meeting of the American Diabetes Association. But based on the preliminary data, Pfizer is comfortable testing a higher dose in Phase 3. The planned pivotal test of PF’3944 will include a high monthly dose of 9.6 mg, which is the equivalent of the 2.4 mg weekly dosing being studied in an ongoing Phase 3 study.
PF’3944 (formerly MET-097i) was the most advanced drug candidate from Metsera, which Pfizer acquired last fall for $10 billion following a protracted bidding war with Novo Nordisk. This peptide was developed with technology that gives the molecule a longer half-life, enabling a longer dosing interval compared to currently available GLP-1 agonists administered as weekly injections.
In a research note, Leerink Partners analyst David Risinger noted that Pfizer did not disclose either the absolute weight loss for the study drug or the placebo response. But he said the data look “slightly inferior” to Eli Lilly’s weekly injectable GLP-1 and GIP agonist, Zepbound. Acknowledging all of the caveats with cross-trial comparisons, Phase 3 results for Zepbound showed 13% placebo-adjusted weight loss at 28 weeks.
Esperion Sets Its Sights on New Areas While Maintaining Commitment to Cardiovascular Health
In a recent interview, Esperion president and CEO, Sheldon Koenig talks about the reality of statin intolerance and his company’s expansion into new diseases
Pfizer’s obesity pipeline includes drugs that target the amylin and GIP receptors. Soon after the Metsera acquisition closed, Pfizer licensed rights to an oral GLP-1 drug candidate from YaoPharma. Plans for this pipeline span more than 20 trials this year, testing these drugs as monotherapies and in combinations. PF’3944 alone will be evaluated in 10 Phase 3 studies.
PF’3944’s Phase 2b readout came alongside Pfizer’s release of full year 2025 financial results. In the conference call to discuss the results, Chief Scientific Officer Chris Boshoff said the long-acting GLP-1 agonist is the foundation for Pfizer’s obesity portfolio.
“We’re primed to execute across an expansive Phase 3 program for ’3944 targeting potential approvals starting in 2028,” he said. “And we are pursuing differentiated combination approaches with earlier-stage agents that have the potential to deliver greater optionality to address the diverse unmet needs of patients.”
Photo: Peter Dazeley, Getty Images