Shedding fat without losing muscle is Lilly’s next weight-loss target

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Indianapolis-based Eli Lilly and Co. will study its blockbuster diabetes drug Mounjaro in combination with an experimental muscle-loss treatment as it searches for ways to help patients maintain muscle while losing weight.

The sheer amount of weight patients are shedding from Mounjaro and similar GLP-1 medications has raised concern that it isn’t just fat melting away, but potentially vital muscle and bone that play key roles in regulating metabolism and preventing injury, particularly in older adults.

Lilly’s clinical development arm, called Chorus, will run a trial with BioAge Labs, a closely held California biotechnology company whose experimental drug azelaprag has shown early promise in preventing muscle atrophy in older adults who’ve been on bed rest.

Lilly and BioAge will test the combination in a mid-stage study starting in mid-2024. BioAge’s drug mimics the action of apelin, a hormone produced during exercise that enhances metabolism and muscle function, but decreases with age.

Amgen Inc. initially developed the drug for heart failure, but abandoned it after it failed an early trial. BioAge, however, saw azelaprag’s promise in another area: aging.

“A lot of benefits seem to be unlocked in an obesity context,” Kristen Fortney, BioAge’s chief executive officer and co-founder, said in an interview.

Biotech companies have been struggling to woo investors as high interest rates drive them away from what’s viewed as a risky industry. Fortney sees obesity as a bright spot, particularly as companies like Lilly and rival Novo Nordisk A/S explore using their weight-loss therapies to treat heart disease and other related conditions.

“That’s what we’re betting on at BioAge,” she said.

This isn’t Lilly’s first foray into studying the effects of a muscle mass treatment.

Preserving muscle

Lilly acquired obesity startup Versanis Bio for as much as $2 billion in July for the same reason it’s partnering with BioAge. Versanis’ experimental drug aims to help people lose weight while preserving muscle mass. The company is studying the candidate on its own and in combination with semaglutide, Novo’s hit obesity drug. Lilly plans to study the Versanis drug in combination with Mounjaro, which is slated for approval for weight loss by the end of the year.

“Lilly is making bold investments to expand our access to external innovation,” Lilly spokeswoman Stefanie Prodouz said in a statement. “We seek opportunities that both support and complement our areas of expertise.”

Muscle-mass preservation is becoming a hot new area in obesity medicine. Ania Jastreboff, the director of the Yale Obesity Research Center who has led key Mounjaro studies for Lilly, said at a conference that improving the quality, not just the quantity, of weight loss is an essential next step.

Some muscle loss is expected when a person loses weight. Normally about a quarter of the weight lost comes from lean mass. That’s a problem for anyone shedding pounds, but potentially dangerous for seniors for whom a decline in muscle and bone can reduce mobility and strength and accelerate frailty.

Experts aren’t clear on just how big of a problem this is for older people taking diabetes and weight-loss drugs like Mounjaro and Wegovy. In a clinical trial of semaglutide, the active ingredient in Novo’s Ozempic and Wegovy, researchers found that on average, people lost around 15 pounds of lean muscle and 23 pounds of fat during a 68-week trial. The average age in that group of people was 52.

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