Pfizer’s High-Stakes Bet on Metsera Shows Early Promise
Pfizer’s $4.9 billion bet on obesity drugmaker Metsera is beginning to show its rationale. New mid-stage data released this week tied the biotech’s lead GLP-1 agonist to double-digit weight loss with what the company described as potentially superior tolerability compared with established competitors.
The drug, MET-097i, was the key asset driving Pfizer’s acquisition of Metsera, announced last week. In the phase 2b Vesper-1 trial, a 1.2-mg weekly dose produced a placebo-subtracted mean weight loss of 14.1% at 28 weeks among 54 patients with overweight or obesity, according to data presented Monday.
Competitive with Wegovy and Beyond
While cross-trial comparisons have limitations, MET-097i’s early performance positions it near or ahead of Novo Nordisk’s semaglutide and Eli Lilly’s tirzepatide, the two dominant players in the GLP-1 field. Novo’s Wegovy, given at 2.4 mg weekly, was linked to 9.6% and 12% weight loss at 28 weeks in two separate studies. Lilly’s tirzepatide, marketed as Mounjaro and Zepbound, has reported higher efficacy at later timepoints, but Metsera said exploratory 36-week data suggest MET-097i’s weight-loss curve had not yet plateaued.
“This gives us a high degree of confidence that doses of MET-097i could match or exceed the performance of tirzepatide 15 mg at steady state,” the company said in its release.
Focus on Tolerability
Beyond efficacy, Metsera emphasized tolerability as a key differentiator. In Vesper-1, only two of 239 participants discontinued therapy due to adverse events. By comparison, about 4.5% of patients on semaglutide discontinued in one prior trial due to gastrointestinal side effects.
Data from a second trial, Vesper-3, tested monthly dosing schedules. Among 53 patients titrated from 0.4 mg up to 1.2 mg, gastrointestinal effects were modest: a 13% increased risk of nausea and 11% increased risk of vomiting versus placebo, with diarrhea risk described as minimal.
Chief Medical Officer Steve Marso, M.D., said the results confirm MET-097i’s potential to deliver “competitive efficacy with category-leading scalability, tolerability, and convenience.”
Pfizer’s Obesity Ambitions
The results arrive at a critical time for Pfizer, which has struggled to gain a foothold in obesity after halting development of its twice-daily oral GLP-1 candidate danuglipron due to tolerability concerns. The company is under pressure to diversify revenue as COVID-19 vaccine sales decline.
The $4.9 billion upfront cash acquisition of Metsera marked one of Pfizer’s largest moves into the obesity market, bringing in not only MET-097i but also other early-stage assets. Analysts view the deal as a bid to catch up with Novo and Lilly, who together have defined the commercial and clinical bar for the class.
Obesity care is projected to become a $100 billion market by the early 2030s, with payers, providers and manufacturers grappling over access and pricing. With Wegovy and Zepbound facing ongoing supply constraints, new entrants with strong efficacy and better tolerability profiles could find opportunities to compete.
Metsera said it plans to advance MET-097i into later-stage development, with Pfizer expected to take the lead on clinical and regulatory strategy following the acquisition’s close. Timelines for a phase 3 program have not been disclosed.
For Pfizer, the latest results bolster the strategic case for the acquisition, while raising expectations that the company can re-enter a field now dominated by two rivals. For patients and providers, the promise of additional GLP-1 options with improved tolerability could help expand long-term adherence to obesity treatments.
Pfizer’s decision to acquire Metsera rather than to originate a new obesity drug in house underscores how fiercely competitive — and capital-intensive — this space has become. In prior years, Pfizer had explored its own GLP-1 and related programs but faced setbacks, especially around tolerability and safety.
