Atrogi’s muscle drug shows early power signal ahead of Phase 2
Swedish biotech Atrogi says its oral drug ATR-258 increased lower-extremity muscle power by about 13% after eight weeks in a study of 13 people with overweight or obesity. Participants also lost an average of 1.1 kg of fat mass and gained 0.8 kg of lean mass.
Why it matters: Developers of weight-loss treatments are looking for ways to preserve lean mass as people lose fat. Despite being early, Atrogi’s results raise the possibility that ATR-258 could improve muscle performance during weight-loss treatment or in conditions affecting muscle function.
How it works: ATR-258 acts on a β2-adrenergic receptor pathway in skeletal muscle, favoring signaling through a protein called GRK2. Earlier research published in Cell described the mechanism and reported that the candidate was well tolerated in a placebo-controlled Phase 1 trial.
Zoom in: The new investigator-initiated study tested three ascending dose levels. It was open-label and had no control group. Atrogi said the drug was well tolerated.
- The 13% improvement in lower-extremity muscle power was measured during a six-second maximal effort on a stationary bike. A company spokesperson explained to European Biotechnology that the gain could translate into tasks such as rising from a chair, while acknowledging that “at this stage this is speculation and must be tested.”
- Regarding the change in fat and lean mass, the company said that “the amount of fat lost and lean mass gained essentially cancel out, meaning that over 8 weeks in this population, body composition change masks body weight loss.”
What they’re saying: “For context, this function increase is more than has been reported (almost twice) for a similar duration of resistance training. One can calculate that it would represent a reversal of 4-5 years of age-related muscle function loss if the improvement were transferred to a population with sarcopenia,” explained the spokesperson.
What’s next: Atrogi plans to start a Phase 2 trial in 2027. According to the company, one option is to test ATR-258 alongside a GLP-1-based weight-loss drug; another is to study people whose main challenge is declining muscle function.
- For a combination trial with GLP-1s, the company said it would seek “more than 5% body weight reduction, with less than 15% of the weight lost being lean mass.” If it studies age-related muscle loss instead, it would focus on functional measures, including walking speed.
- “What we hope to see over a longer study in more patients is body composition continuing and indications of benefit to the participant in terms of exact body weight changes and functional improvements that are not only measured in the clinic but also reported from daily life,” concluded the company.
