Metsera's experimental obesity drug targeting the amylin hormone has demonstrated significant weight loss potential in early clinical testing, with patients achieving 8.4% placebo-adjusted weight reduction at 36 weeks using a once-monthly injection regimen. The Phase I results, announced Monday, sent the biotech's shares up as much as 20% as investors recognized the potential for a differentiated approach in the competitive weight loss market.
Phase I Trial Results Show Promise
The Phase I study evaluated MET-233i, an ultra-long-acting amylin analog, in 80 patients who were overweight or obese but did not have type 2 diabetes. At the highest tested dose of 1.2 milligrams administered monthly, patients experienced an average weight reduction of 8.4% relative to placebo at 36 weeks, with some individual responses reaching as high as 10.2%.
The drug's pharmacokinetic profile revealed a half-life of 19 days, which supports the once-monthly dosing regimen and distinguishes it from current weekly weight loss treatments. Notably, patients treated with MET-233i maintained their weight loss for more than four weeks, demonstrating the therapy's ultra-long-acting characteristics.
In a separate arm of the trial testing single-dose administration, patients receiving the highest dose of 2.4 milligrams experienced an average of 5.3% placebo-adjusted weight loss at one week. Additionally, in a five-week dosing regimen, the highest dose of 1.2 milligrams produced 8.4% placebo-adjusted weight loss at the end of the treatment period.
Safety Profile and Tolerability
MET-233i demonstrated a relatively clean safety profile with no severe or serious toxicities reported to date. Gastrointestinal side effects, while typical of the amylin drug class, were mild and limited to the first week of dosing. This pattern suggests rapid onset of tolerance, potentially offering advantages over existing treatments that require ongoing management of gastrointestinal symptoms.
Amylin Mechanism and Market Positioning
MET-233i is designed as an analog of the amylin protein, a pancreatic hormone that works with insulin to slow gastric emptying and lower blood glucose levels. Unlike the more established GLP-1 drugs, amylin therapies could potentially offer several advantages, including better tolerability and lower loss of lean mass.
Guggenheim Partners analysts have identified MET-233i as the only potential once-monthly amylin in clinical development and estimated that the market for ultra-long-acting injectable incretin therapies could reach $19 billion by 2035. The drug could also be combined with Metsera's other pipeline assets targeting GIP and glucagon, opening pathways to differentiated products and market segmentation.
Development Timeline and Future Studies
With Monday's positive data, Metsera plans to continue its monotherapy study for MET-233i, with topline findings expected later this year. The company is also testing the amylin injection in combination with its ultra-long-acting GLP-1 therapy MET-097i, with data from the combination trial expected as early as year-end 2025 or early 2026.
Competitive Landscape Context
The amylin space has gained increased attention following mixed results from Novo Nordisk's CagriSema, a combination of semaglutide and the long-acting amylin analog cagrilintide. In December 2024, CagriSema's Phase III REDEFINE 1 study showed 22.7% weight loss at 68 weeks, falling short of the expected 25% and triggering a $72 billion market cap decline for Novo Nordisk.
Guggenheim analysts noted that REDEFINE 1's flexible dosing protocol resulted in only 56% of patients reaching the maximum CagriSema dose, calling this an "unforced error" that underestimated the drug's full potential. However, they believe Novo's results validated the amylin mechanism in obesity while creating opportunities for differentiated competitors like Metsera's ultra-long-acting approach.
