Metsera, Clive Meanwell's new obesity biotech, reveals early GLP-1 data, plans Phase 3 next year

Metsera, a newly established and well-financed obesity biotech firm from Population Health Partners and ARCH Venture Partners, has recently shared its initial clinical data just a few months after securing $290 million and developing a comprehensive pipeline of weight loss medications.

The New York City-based company announced that its GLP-1 receptor agonist, a long-acting injectable named MET-097, demonstrated a 7.5% reduction in some patients' body weight from baseline by day 36 in a Phase 1 clinical trial. This measurement was taken one week after a specific group of patients received their fifth and final dose of 1.2 mg. Four weeks after the final dose was administered, the cumulative weight loss increased to 8.1% for that group in the 125-person placebo-controlled study.

CEO Clive Meanwell expressed confidence in the competitiveness of their product. The Phase 1 study explored various doses ranging from 0.16 mg to 1.6 mg in single-ascending and multiple-ascending dose trials. According to Meanwell, the highest dose of 1.6 mg resulted in significant nausea and vomiting, rendering it unsuitable for standard care. However, at a 1.2 mg dose, the side effects were comparable to others in the same class, with most adverse events being mild and temporary, including "a few hours at most" of nausea. Only a small number of patients experienced diarrhea.

The clinical trial was carried out in the Kansas City area by the CRO Altasciences, owned by Novo Holdings. Novo Holdings is the controlling shareholder of Novo Nordisk, a market leader in obesity treatment, and conducts some early-stage testing for the Danish pharmaceutical giant.

Despite these promising early results, Metsera acknowledges the need for replication in a larger and more extended Phase 2b study. This next phase, expected to last 13 weeks, might involve head-to-head comparisons of Metsera's drug candidate against leading obesity medications. The firm is still deliberating on the appropriate dose to test in the upcoming trial, considering either 0.8 mg or 1.2 mg.

Other companies have reported higher levels of weight loss with different drug types and longer treatment durations. For instance, Zealand Pharma's GLP-1/GLP-2 receptor dual agonist achieved an 8.3% placebo-adjusted mean weight reduction over 13 weeks, and Roche's daily pill recorded a 7.3% weight loss in one month.

In the context of long-term studies on GLP-1 receptor agonists, Meanwell suggested that weight loss should ideally reach "high-teens, low-20s." Metsera is also developing an earlier-stage amylin-calcitonin receptor agonist in combination with its GLP-1, which, if successful, could achieve a 25% to 30% weight loss, making it highly competitive.

While Metsera lags behind established giants like Novo Nordisk and Eli Lilly, the company is optimistic about its potential to claim a niche in the obesity market with a once-monthly treatment that boasts a significantly longer half-life. Notably, MET-097, developed from the acquisition of UK startup Zihipp, has a half-life of 380 hours. This is in contrast to Novo, which halted a Phase 1 trial of a once-monthly GLP-1/GIP agonist due to portfolio prioritization.

Currently, the leading obesity treatments, Novo's Wegovy and Lilly's Zepbound, require once-weekly injections. These companies are also exploring longer-duration treatment options and have recently acquired several obesity startups to gain access to muscle-preserving medications or other novel mechanisms. Novo's recent venture into a previously shelved CB1 class faced challenges due to neuropsychiatric side effects that overshadowed its efficacy.

Meanwell emphasized that Metsera aims to eliminate the need for a titration schedule to help patients adjust to higher doses. The company is in the process of finalizing its Phase 2b trial, which is set to commence next quarter in the US. Data from this trial is anticipated by next summer, potentially paving the way for a Phase 3 trial to begin in the latter half of the following year.