Metsera, Inc. has announced positive topline results from its Phase 1 clinical trial of MET-097, a novel, ultra long-acting injectable GLP-1 receptor agonist. The study demonstrated significant and durable weight loss in healthy, non-diabetic, overweight or obese adult participants, suggesting the potential for a once-monthly dosing regimen.
The randomized, placebo-controlled, double-blind Phase 1 trial evaluated the tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneous MET-097 in 125 participants. MET-097 was administered in single doses ranging from 0.16 mg to 1.6 mg and weekly doses from 0.2 mg to 1.2 mg, given five times without titration.
Key Findings from the Phase 1 Trial
One of the key findings was the dose-linear pharmacokinetics of MET-097, exhibiting a half-life of 380 hours. This extended half-life is attributed to Metsera's proprietary HALO™ peptide lipidation platform technology, which facilitates ultra-long clearance. According to Brian Hubbard, Ph.D., chief scientific officer of Metsera, this translates to a 2-3 fold longer half-life than currently available and investigational nutrient-stimulated hormone (NuSH) products.
The trial also revealed a dose-dependent change in body weight from baseline. At the 1.2 mg dose, participants experienced a 7.5% reduction in body weight at day 36, one week after the final dose. Cumulative weight loss at the same dose reached 8.1% at day 57, four weeks post-treatment, indicating a sustained pharmacodynamic effect consistent with the observed 380-hour half-life.
Safety and Tolerability
Regarding safety, gastrointestinal adverse events were dose-related, mostly mild, and transient, aligning with the profiles of marketed and clinical-stage NuSH compounds. Notably, there were no severe treatment-related adverse events and no treatment-related study drug discontinuations.
Implications and Future Directions
Steve Marso, M.D., chief medical officer of Metsera, expressed enthusiasm about the results, stating that they position MET-097 as a potent and well-tolerated GLP-1 drug candidate. He highlighted the potential for no titration and once-monthly dosing, which could offer a more convenient, scalable, and better-tolerated approach to GLP-1 medicine administration.
Metsera plans to initiate a Phase 2b trial of MET-097 in Q4 2024, with data expected in the first half of 2025. This trial will further investigate the efficacy and safety of MET-097 in a larger patient population.
Competitive Landscape
These results arrive amidst a competitive landscape of next-generation weight loss therapies. Other companies, including Novo Nordisk and Roche, are also developing GLP-1 receptor agonists and related compounds. Metsera's MET-097 distinguishes itself with its ultra-long half-life and potential for convenient monthly dosing, offering a unique value proposition in the evolving weight loss treatment market.
