Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans

A hormone-mimicking weight-loss drug

29 March 2021

An experimental drug designed to mimic a metabolic hormone is showing early promise as an anti-obesity treatment.

A team from Genentech, a Roche subsidiary, designed a bispecific antibody drug to bind and activate two receptors normally triggered by fibroblast growth factor 21 (FGF21), a hormone involved in regulating fat and sugar use.

The researchers first evaluated the drug in obese monkeys. A single injection caused profound weight loss, with marked reductions in food consumption to boot.

They next tested the therapy in 71 obese or overweight individuals, each of whom received a single injection of the drug or a placebo under the skin. The drug was well tolerated, improved blood measures of cardiometabolic health and, compared to the placebo, caused significant reductions in body weight. Both caloric intake and a desire for sweet foods decreased as well.

Roche is now investigating the drug in larger trials involving people with an advanced form of non-alcoholic fatty liver disease.

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References

1. PNAS 117, 28992-29000 (2020). doi: 10.1073/pnas.2012073117