MET-097i supports monthly dosing for obesity

MET-097i reduces body weight by up to 20% with minimal gastrointestinal events

Metsera, Inc. announced positive data from a 12-week phase 2a clinical trial of MET-097i, its potential once-monthly, ultra-long acting, subcutaneously injectable, fully-biased, GLP-1 receptor agonist (RA).

The randomized, double-blind, placebo-controlled trial enrolled 120 participants with obesity and overweight who did not have type 2 diabetes. MET-097i was tested in five cohorts of 24 participants (20 active drug, 4 placebo). In four cohorts, participants received 0.6 mg, 0.8 mg, 1.0 mg, or 1.2 mg weekly, without titration, for 12 weeks. The fifth cohort received escalating weekly doses: 0.4 mg for 4 weeks, then 0.8 mg for 4 weeks, then 1.2 mg for 4 weeks. At week 13, all participants received either a two- or four-fold step-up in dose to assess tolerability of switching to a pharmacologically matched, potential monthly dose.

Weight loss was dose-dependent, with substantial reductions in mean body weight of 11.3% (placebo-adjusted) and individual responses as high as ~20% in the 1.2 mg dose cohort after 12 weekly doses. A weight loss plateau was not reached, suggesting additional weight loss potential with longer-term dosing. All cohorts achieved clinically meaningful and statistically significant weight loss after 12 weeks.

MET-097i was generally well tolerated across all dose groups. Gastrointestinal adverse events (AEs) were mild or moderate and short-lived. In the fifth cohort, which received titrated doses, only one case of mild, transient nausea and two cases of mild, transient vomiting were observed. Mean body weight loss of 6.3% (placebo-adjusted) was observed in this dose-escalated cohort.

Pharmacologic exposure accumulated approximately four-fold over 12 weeks in the titration-free cohorts, driven by the 15–16-day half-life of MET-097i, reinforcing the potential for titration-free dosing. At week 13, step-up to a four-fold higher dose was well tolerated in all cohorts, supporting the feasibility of monthly dosing with this ultra-long acting GLP-1RA.

Metsera plans to launch an additional study in early 2025 to confirm monthly dosing across multiple doses. In parallel, the company’s phase 2b trial of MET-097i in people with obesity or overweight has been fully enrolled with 239 participants. Topline data from this trial are expected in mid-2025. Additional trials exploring MET-097i in people with obesity, overweight, and type 2 diabetes, including monthly dosing, are also expected in 2025. If successful, Metsera plans to initiate phase 3 trials shortly thereafter.

“Taken together, these data suggest that MET-097i has the potential to be a foundational therapy for people with obesity and overweight, by virtue of its effectiveness, compelling tolerability profile and flexible options for dosing, including titration-free weekly dosing and monthly dosing,” said John Buse, Verne S. Caviness Distinguished Professor and Director of the UNC Diabetes Center at University of North Carolina School of Medicine, USA.

“These data strengthen our view of MET-097i as the potential first ultra-long acting GLP-1RA,” added Steve Marso, Chief Medical Officer of Metsera. “The powerful reductions in weight affirm our earlier studies. We are also excited by the emerging tolerability and dosing profile of MET-097i, which may offer versatility and meaningful advantages for patients.”

What is MET-097i, and how is it administered?

MET-097i is a once-monthly, ultra-long acting, subcutaneously injectable, fully-biased GLP-1 receptor agonist.

What were the key findings from the phase 2a trial of MET-097i?

MET 097i achieved up to 20% individual weight loss and 11.3% mean placebo-adjusted weight loss after 12 weeks of weekly dosing.

How was the MET-097i phase 2a trial structured?

The trial enrolled 120 participants across five cohorts, testing weekly doses with and without titration, followed by a step-up dose at week 13.

Was MET-097i well tolerated during the trial?

Yes, MET-097i was generally well tolerated. Mild and transient gastrointestinal adverse events were reported, especially in the titrated cohort.

What are Metsera’s next steps for MET 097i?

Metsera plans a new study in early 2025 to confirm monthly dosing and expects topline phase 2b data in mid-2025, with phase 3 trials to follow.