“This class of drugs [GLP-1 agonists], though, often causes severe nausea in early weeks and doesn’t lead to significant weight loss in everyone. There’s growing concern that in addition to fat loss, the drugs lead to muscle loss that could prove detrimental for older patients. And for most people, the costly drugs may need to be taken forever to sustain the effects. [..]
Versanis’ bimagrumab, which increases muscle while cutting fat, stands out because all currently available obesity drugs lead to muscle loss. In a trial for Wegovy, for example, about 40% of the weight that people lost was lean mass. Some doctors worry that elderly people taking the drug could become frailer and more vulnerable to accidents.
Bimagrumab works by blocking proteins from binding to receptors called activin type II. When certain proteins in the body bind to those receptors, they inhibit muscle growth and are thought to also promote fat accumulation.
As an added benefit, building muscle may lead to more durable weight loss. [..]
Data from earlier trials of bimagrumab show that people maintained weight and fat loss for 12 weeks after stopping the therapy. In contrast, people tend to quickly regain weight after they stop taking Wegovy. [..]
Versanis isn’t the only startup that believes it can target fat specifically. Resalis Therapeutics, a startup out of Italy, is developing an RNA-based treatment designed to inhibit microRNA called miR-22. In turn, that changes the metabolism of fatty compounds known as lipids, increases energy expenditure, and more. In preclinical studies, company executives said they saw a reduction only in fat deposits, not lean muscle. Both Versanis and Resalis are developing their drugs to be injections. [..]
Daniel Drucker, a professor at the University of Toronto who helped discover GLP-1, said it’s too early to say if bimagrumab will offer an advantage. More data is needed, and it’s also not yet clear if muscle loss on drugs like Wegovy actually poses problems for patients, he said.
“It’s very early for bimagrumab, it’s a very innovative observation, it’s a very unique molecule,” said Drucker [..]. “But to me, it’s not yet clear that there’s a real unmet need that needs to be fulfilled.”
[..] “the bar is now set very high” after the success of drugs like Wegovy, said [Randy] Seeley, the University of Michigan obesity research director. New drugs will probably have to show at least 20% weight loss and some benefit to heart health in order to compete, he said. Novo is currently testing Wegovy to see if it protects or boosts cardiovascular health, but its underlying ingredient has already been shown to cut the risk of heart attacks and strokes in people with diabetes. [..]
Resalis, the Italian startup targeting miR-22, is also testing its drug in combination with semaglutide. So far, it’s finding the combination leads to better weight control over time in preclinical trials. Executives attribute it to the fact that, while semaglutide dampens appetite, leading to a quick drop in weight, Resalis’ lead drug, RES-101, is rewiring metabolism and energy expenditure.
CEO Alessandro Toniolo likened it to how medical professionals treat inflammatory diseases today: Physicians used to rely on painkillers to numb the discomfort of rheumatoid arthritis and other inflammatory diseases, but can now prescribe medications that address the underlying biological problems behind the conditions. But many still prescribe both, to address patients’ short- and long-term needs.
“The market will become more and more crowded, so I think the time is now to develop something orthogonal to GLP-1s,” Toniolo said. Resalis hopes to start clinical trials next year.”
Full article, E Chen and A DeAngelis, STAT News, 2023.5.1