The GLP-1 agonist at the center of Pfizer’s upfront $4.9 billion buyout of Metsera last week has been tied to 14.1% weight loss at 28 weeks as well as “potentially class-leading tolerability,” according to the biotech.
The injectable candidate, dubbed MET-097i, was the main attraction from the pipeline of obesity drugs that Pfizer secured as part of its acquisition. Metsera kicked off the year by tying MET-097i to weight loss of up to 11.3% after 12 weeks and unveiled longer-term data yesterday.
Specifically, the phase 2b Vesper-1 study assessing weekly dosing of MET-097i demonstrated a mean placebo-subtracted weight loss of 14.1% after 28 weeks for the 54 patients who were overweight or with obesity who received the highest, 1.2-mg, dose of the drug.
While it’s difficult to directly compare weight loss trials, a 2.4-mg weekly dose of semaglutide—the ingredient in Novo Nordisk’s blockbuster Wegovy—has previously been tied to 9.6% and 12% weight loss, respectively, at 28 weeks in two separate trials.
The full effects of MET-097i won’t be seen for a while. Metsera said an exploratory analysis of 36-week data from the study “demonstrated substantial continued weight loss, highlighting that no plateau had been reached.”
Alongside this “competitive efficacy,” Metsera gave equal billing yesterday to MET-097i's tolerability. The biotech also disclosed 12-week interim data from another phase 2b study, called Vesper-3, which is evaluating various monthly dosing options of the drug.
Among the 53 patients who titrated from a 0.4-mg dose to 0.8 mg and then 1.2 mg, there was a “minimal” increased diarrhea risk, while there was a 13% risk difference from placebo for nausea and 11% for vomiting.
The company also pointed out that back in the Vesper-1 study, only two of the 239 participants had discontinued treatment due to adverse events. In contrast, 4.5% of patients who received Novo’s semaglutide in one previous study discontinued their treatment due to gastrointestinal events.
John Buse, M.D., Ph.D., a professor at the UNC School of Medicine, described the efficacy and tolerability of MET-097i as “remarkable” in Metsera’s Sept. 29 release. The real test will be whether the drug can best Eli Lilly’s tirzepatide, marketed as Zepbound in obesity, he suggested.
“To move the needle in the future obesity treatment landscape, a [nutrient-stimulated hormone] analog candidate must meet or exceed the already high efficacy and tolerability bar set by tirzepatide, while further improving convenience and scalability,” Buse added. “MET-097i is the first NuSH analog in late-stage clinical development that I am aware of that is on track to meet these criteria.”
Based on yesterday’s release, it sounds like Metsera also believes MET-097i is up for the tirzepatide challenge. The company said the latest trial results “give Metsera a high degree of confidence that doses of MET-097i could match or exceed the performance of tirzepatide 15 mg at steady state.”
Metsera Chief Medical Officer Steve Marso, M.D., added that the “excellent results” confirm the potential of MET-097i to deliver “competitive efficacy with category-leading scalability, tolerability, and convenience.”
“Based on these data, MET-097i is advancing into phase 3 clinical trials, accelerating its development as the foundational peptide for Metsera’s combination, oral, and prodrug programs,” Marso said.
The readouts back up Pfizer’s decision to buy the biotech last week, which analysts applauded as a way for the Big Pharma to “meaningfully make Pfizer a more credible threat in the obesity landscape with Metsera's long-acting injectable and oral agents.”
A global phase 3 study of MET-097i is penciled in for later this year, while 28-week data from the Vesper-3 study of monthly dosing are expected either later in 2025 or early 2026.
Metsera’s pipeline also includes a monthly injectable amylin analog—which could be combined with MET-097i—and an oral GLP-1 that is designed to drive more weight loss than small molecules and avoid the scalability challenges of other oral peptides.