Metsera ties long-acting GLP-1 shot to 7.5% weight loss in 36 days, considers monthly dosing

Metsera has recently introduced phase 1 data for its new GLP-1 receptor agonist, MET-097, showcasing a 7.5% reduction in body weight after 36 days compared to baseline. This injection has shown "significant and durable" weight loss, as stated in a company release dated September 24. The ongoing trial involves 125 nondiabetic overweight or obese adults who were given initial doses ranging from 0.16 mg to 1.6 mg, followed by weekly doses between 0.2 mg and 1.2 mg for five weeks. Weight loss was dose-dependent, with the 1.2 mg weekly dose group experiencing a 7.5% reduction by day 36. This reduction was measured a week after the final dose and is reportedly on par with or better than some approved and clinical-stage GLP-1/GIP compounds.

This data echoes the results from Roche's oral GLP-1 prospect CT-996, which also linked to a 7.3% weight loss after four weeks. However, the timeframes for weight loss drug trials can vary widely, making direct comparisons challenging. For instance, Novo Nordisk’s GLP-1 agonist Wegovy achieved an average weight reduction of 14.9% over 68 weeks in the STEP-1 phase 3 trial, and another study called OASIS showed a 15% weight loss over the same period. Eli Lilly’s dual GIP/GLP-1 agonist Zepbound induced a 22.9% weight loss over a more extended period of 176 weeks.

For patients receiving the 1.2-mg dose of Metsera’s investigational injection, weight loss continued beyond 36 days, reaching an 8.1% cumulative reduction by day 57, which is four weeks after the final dose. According to Metsera, MET-097’s half-life is 380 hours, nearly 16 days. This long half-life is attributed to Metsera’s proprietary HALO technology platform, which Chief Scientific Officer Brian Hubbard, Ph.D., claims validates the science behind Metsera's discovery platform. Hubbard believes this platform can produce nutrient-stimulated hormone (NuSH) analogs with half-lives two to three times longer than current marketed and investigational peptide NuSH analogs, comparable to antibody-conjugated NuSH analogs.

Regarding safety, the trial reported that gastrointestinal adverse events were dose-related but mostly mild. No severe treatment-related adverse events or study drug discontinuations were noted. Despite the trial's weekly dosing regimen, Metsera's new phase 1 data suggest that a once-monthly dosing schedule could be feasible, supported by the observed half-life, which is the longest recorded for any peptide GLP-1 construct and comparable to antibody-peptide conjugates like Amgen's candidate MariTide. The durability and increasing weight loss observed at 57 days also support this dosing regimen.

The early-stage results present MET-097 as an ultra-long acting, potent, and well-tolerated GLP-1 drug candidate, according to Metsera Chief Medical Officer Steve Marso, M.D. Marso highlighted the potential for no titration and once-monthly dosing, which could make GLP-1 medicines more convenient, scalable, and better tolerated.

Metsera is preparing to launch a phase 2b trial for MET-097 this year, with data anticipated in the first half of 2025. Founded in 2022 by Population Health Partners and Arch Venture Partners, Metsera has raised $322 million so far and is led by CEO Clive Meanwell, M.D., who has a notable industry background, including founding The Medicines Company, which was acquired by Novartis for $9.7 billion in 2019.

Additionally, Metsera’s preclinical pipeline includes a dual amylin/calcitonin receptor agonist (DACRA) designed to be combined with MET-097, a unimolecular GGG (GLP-1, GIP, glucagon) for combo use with DACRA, and two IND-ready candidates from the company’s oral peptide delivery platform. Meanwell emphasizes the company's aim to develop a suite of multi-target molecules that offer increased efficacy with fewer side effects, believing that the future of metabolic disease treatment lies in combination therapies.