Metsera has linked its amylin analog to 8.4% placebo-adjusted weight loss at Day 36, advancing its push to develop an ultralong-acting challenger to candidates in development at AbbVie, Eli Lilly, Novo Nordisk and Roche.
Interest in amylin analogs has surged in recent months. In March, AbbVie paid $350 million upfront for a phase 1 prospect, and Roche offered $1.65 billion in confirmed fees for co-development rights to Zealand Pharma’s challenger. The flurry of activity followed data linking Zealand’s amylin analog petrelintide to placebo-adjusted weight loss of up to 6.9% after 16 weeks of dosing.
Metsera has ceded a head start to its rivals. But, having shown its drug candidate MET-233i is more potent than Novo’s amylin analog in preclinical tests, the biotech went into the phase 1 readout hoping to report a differentiated profile that could support monthly dosing.
The study tested a range of single and multiple doses in 80 nondiabetic people with obesity or who are overweight. Compared to placebo, people who received five weekly 1.2-mg doses lost 8.4% of their body weight by Day 36. That was the top dose given multiple times. Metsera tested single doses up to 2.4 mg, achieving placebo-adjusted weight loss of up to 5.3% at Day 8.
The data look competitive, with the caveat that cross-trial comparisons can be misleading. Zealand saw lower weight loss despite dosing patients for longer. Weight loss typically increases over time, suggesting Metsera will have extended its advantage over Zealand by the time it has comparable 16-week data. Novo saw placebo-adjusted mean weight loss of 5.9% at Week 16 of a trial of its amylin, cagrilintide.
There was no dose titration in the Metsera trial, a decision that would typically boost efficacy at the cost of tolerability. Metsera said gastrointestinal adverse events in the multiple ascending dose portion of its trial were mild, dose-dependent and primarily confined to the first week of dosing. Tolerability at the anticipated MET-233i starting doses was placebo-like, according to the company.
Metsera reported a half-life of 19 days, prompting the biotech to claim MET-233i has the “most durable pharmacokinetic profile of any amylin analog in clinical development reported to date.” The profile could support monthly dosing. Metsera’s GLP-1 drug candidate could also support monthly dosing. And, with the molecules’ exposure profiles lining up, the biotech believes a once-monthly combination is viable.
A study that is testing co-administration of the amylin and GLP-1 candidates is scheduled to report data early next year. Metsera is aiming to deliver data from a MET-233i monotherapy trial late this year. The single-agent study is testing the effect of 12 weekly doses of MET-233i with dose titration, followed by exposure-matched monthly doses.