Metsera’s new obesity data mean Pfizer has side effect and efficacy questions to answer Elizabeth Cairns Senior biopharma journalist Pfizer’s back in obesity. Or is it?
The hotly-awaited Phase 2b readout of the long-acting GLP-1 shot developed by Metsera, the biotech Pfizer said it would buy for $4.9 billion last week, seems good at first glance after its release late Monday. But look closer, and the results are trickier to interpret.
The data are from two trials of Metsera’s candidate, called MET-097i, in nondiabetic patients with obesity. In the first of these, called VESPER-1, weight loss came in at 14.1% at around six and a half months when adjusted for placebo, on the highest dose of 1.2 mg weekly.
Metsera seems to have hit its stated target here, which was similar weight loss to the highest weekly dose of Eli Lilly’s GIP/GLP-1 therapy Zepbound, which reached roughly 14% placebo-adjusted weight loss in its pivotal trial at an equivalent time point.
But the company hasn’t yet shared data showing that it has a single dosing approach that doesn’t come with a set of side effects that could hamper the use of the drugs. It said only that “higher doses” of MET-097i in VESPER-1 had similar tolerability to approved products that used “prolonged” titration regimens. Two of the 239 VESPER-1 participants who took the drug discontinued treatment due to adverse events.
If the 14.1% placebo-adjusted weight loss figure came with markedly higher side effect rates than Zepbound, MET-097i might not be so competitive.
The other MET-097i doses tested in VESPER-1, 0.4 mg, 0.6 mg and 0.9 mg weekly, yielded respective placebo-adjusted weight loss figures of 8%, 10% and 13% at 28 weeks, also highly respectable. However, Metsera made no claims for statistical significance versus placebo in its data release.
It did say that after VESPER-1’s 28-week primary endpoint, patients given the GLP-1 demonstrated “substantial continued weight loss” out to 36 weeks.
Tolerability Pfizer needs MET-097i to be as good as Zepbound on both efficacy and tolerability, and ideally better, if its acquisition is to be seen as a truly winning bet.
But an answer on this point may have to wait longer. A different trial of the drug yielded tolerability results, but no efficacy data were reported. In VESPER-3, the dose was gradually increased — a way of administering a drug that works to keep adverse event rates lower than if patients received the same dose throughout, as they did in VESPER-1.
In a VESPER-3 trial cohort, which had their weekly doses titrated from 0.4 mg to 0.8 mg to 1.2 mg over the course of three months, 24% and 13% of patients had nausea and vomiting, respectively, when calculated from figures provided in the Metsera release. The rates of nausea and vomiting were 11% and 2%, respectively, with placebo.
In a VESPER-3 cohort that received a 0.8 mg weekly dose with no titration, nausea and vomiting were seen in 35% and 17% of patients, respectively. This raises the possibility that the rates of these side effects were higher still in VESPER-1.
For comparison, in Zepbound’s pivotal trial, 31% and 12% of patients taking the 15 mg dose had nausea and vomiting, respectively.
The company said it has picked the doses that would be tested in Phase 3 trials, though it didn’t disclose which it chose beyond saying it has a “high degree of confidence” that the drug could match or exceed Zepbound’s top dose.
In VESPER-3 MET-097i was given weekly for the first three months, but after that, patients will receive the drug monthly. Results from this part of the trial should come late this year or early next.
The biotech said that Phase 3 studies would begin by the end of the year. In July, the company’s management told Endpoints News that it was envisioning two Phase 3 trials in a total of 4,500 patients.
Another Phase 2b trial, VESPER-2, is testing MET-097i in participants with type 2 diabetes as well as obesity. Topline data are expected in early 2026.
Editor’s note: This post has been updated to include more detailed side effect data from the VESPER-3 trial and to correct an error about Phase 3 timing and calculations of AE rates. An earlier version of the piece said that Metsera had previously planned Phase 3 trials of MET-097i to start after the monthly data from VESPER-3 had reported; that referred to Phase 3 trials of monthly dosing. Phase 3 trials with the weekly regimen were always planned for 2o25.
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