Nutritionist calculating body mass index of woman for obesity treatment in a clinic room. Current research shows the gut microbiome may also influence risk for obesity.
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Early data suggest Amgen’s experimental weight-loss drug MariTide (maridebart cafraglutide) produces similar effects but is longer-lasting than current market leaders, and blockbusters, glucagon-like peptide-1 inhibitors Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide).

The study was published in Nature Metabolism this week. The lead authors are Murielle M. Véniant and Shu-Chen Lu of Amgen Research. 

The rise of incretin-based therapeutics has revolutionized the management of type 2 diabetes. Incretins are gut-derived peptide hormones that are rapidly secreted in response to a meal. One of which is glucagon-like peptide-1 (GLP-1).

While they were developed to treat diabetes, these also have notable effects on weight as well. Current incretin therapeutics have also been found to provide improvements in cardiovascular health. In one recent clinical study, for example, patients with heart failure and preserved ejection fraction who received weekly semaglutide injections (2.4 mg) for 52 weeks experienced substantially improved symptoms and physical function compared to placebo group.

According to the WHO, the worldwide prevalence of obesity has nearly tripled since 1975, with 60% of citizens in Europe alone being either overweight or obese.  The world market for anti-obesity drugs is estimated to be worth more than $37B over the next few years. 

The competition in this burgeoning GLP-1 market is fierce. First out of the gate were Novo Nordisk’s Ozempic for diabetes and Wegovy for obesity (both semaglutide). Novo received FDA approval for these products in 2017 and 2021, respectively. Lilly’s Zepbound is the same formula as its type 2 diabetes drug Mounjaro, FDA approved in May 2022, Mounjaro has been used widely off-label to treat obesity. All of these are injectables.

Now it looks like Amgen is in the thick of it.

In this Phase I study, the highest dose of MariTide resulted in a body weight loss of 14.5% by day 85, compared to the placebo group, who gained 1.5% body weight. Even on the lowest dose, patients lost 7.4% of their body weight after just three doses. In earlier trials, Wegovy and Zepbound have shown 15% to 21% weight loss.

MariTide is a bispecific molecule combining a glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist and glucagon-like peptide-1 (GLP-1) receptor agonist. It both activates GLP-1 receptors while blocking receptors of the GIP hormone.  

Formerly, AMG 133, MariTide is a bispecific molecule engineered by conjugating a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides using amino acid linkers. 

This Amgen team confirmed the GIPR antagonist and GLP-1R agonist activities in cell-based systems and reported the ability of MariTide to reduce body weight and improve metabolic markers in obese male mice and cynomolgus monkeys. In the trial, (NCT04478708), MariTide 133 had an acceptable safety and tolerability profile along with pronounced dose-dependent weight loss. In the multiple ascending dose cohorts, weight loss was maintained for up to 150 days after the last dose.

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