Metsera's Amylin Analog Shows Promise in Weight Loss Study, Positioning for Monthly GLP-1 Combo

Metsera, a rising player in the competitive obesity treatment market, has reported encouraging results from a phase 1 study of its amylin analog MET-233i, potentially setting the stage for a monthly combination therapy with a GLP-1 agonist.

Impressive Weight Loss Results

In a study involving 80 non-diabetic individuals with obesity or overweight, MET-233i demonstrated significant efficacy. Participants receiving five weekly 1.2-mg doses experienced a placebo-adjusted weight loss of 8.4% by Day 36. Single doses up to 2.4 mg achieved placebo-adjusted weight loss of up to 5.3% at Day 8.

These results appear competitive within the rapidly evolving amylin analog landscape. Zealand Pharma's petrelintide showed placebo-adjusted weight loss of up to 6.9% after 16 weeks, while Novo Nordisk's cagrilintide achieved 5.9% at Week 16. However, direct comparisons should be approached with caution due to differences in trial designs and durations.

Favorable Pharmacokinetic Profile

Metsera reported a half-life of 19 days for MET-233i, which the company claims is the "most durable pharmacokinetic profile of any amylin analog in clinical development reported to date." This extended half-life could support monthly dosing, aligning with Metsera's GLP-1 drug candidate and potentially enabling a once-monthly combination therapy.

Safety and Tolerability

Despite the absence of dose titration, which typically enhances efficacy at the cost of tolerability, MET-233i demonstrated a promising safety profile. Gastrointestinal adverse events in the multiple ascending dose portion were reported as mild, dose-dependent, and primarily confined to the first week of dosing. Notably, tolerability at the anticipated MET-233i starting doses was described as placebo-like.

Future Development Plans

Metsera is advancing its amylin analog program with two key studies:

1. A MET-233i monotherapy trial testing the effect of 12 weekly doses with dose titration, followed by exposure-matched monthly doses, with data expected late this year.

2. A study co-administering MET-233i with Metsera's GLP-1 candidate, scheduled to report data in early 2026.

These trials aim to further elucidate the potential of MET-233i as both a standalone therapy and in combination with a GLP-1 agonist, potentially offering a novel approach to obesity treatment with less frequent dosing.