Scholar Rock says apitegromab cut lean mass loss during Zepbound treatment in phase 2 trial

Scholar Rock reported June 18 that adding its experimental drug apitegromab to tirzepatide, the molecule sold as Zepbound, roughly halved the share of weight that patients lost as lean muscle rather than fat over 24 weeks in a phase 2 trial ^[2].

In the study, called EMBRAZE, 30.2% of the total weight lost by patients taking tirzepatide alone came from lean mass. When patients also received 10 mg/kg of apitegromab, that figure fell to 14.6% ^[2]. Scholar Rock described the combination as producing "higher quality of weight loss" ^[2].

Put another way, patients on the combination lost 85% of their weight as fat and 15% as lean mass. In the tirzepatide-plus-placebo group, the split was 70% fat and 30% lean mass ^[2].

Total weight loss was slightly lower in the combination group: 12.3% of body weight, compared with 13.4% for tirzepatide plus placebo ^[2]. The release did not say whether that difference was statistically significant, and the trial was designed around lean-mass preservation as its primary endpoint rather than a head-to-head comparison of total weight loss ^[2].

Scholar Rock said apitegromab was "generally well tolerated" and that no patients had serious adverse events or discontinued treatment because of the drug ^[2].

Apitegromab is an inhibitor of myostatin activation ^[2]. Myostatin is a protein that limits muscle growth. Scholar Rock is already seeking FDA approval of the drug for spinal muscular atrophy, a different condition, with a decision date in September ^[2]. That filing followed a phase 3 SMA trial reported in October 2024 that showed a 1.8-point improvement in motor function compared with placebo after 52 weeks ^[2].

"Our platform of highly selective myostatin inhibitors has the potential to support healthier weight loss for millions of patients on GLP therapies by safely preserving lean mass," said Akshay Vaishnaw, president of research and development at Scholar Rock. He added that GLP treatments "can result in substantial loss of lean muscle mass for patients, leading to unwanted health risks" ^[2].

Vaishnaw said the company remains focused on preparing to launch apitegromab for SMA if the FDA approves it ^[2].

Shares of Scholar Rock rose 5% to $32.80 in premarket trading June 18, from a closing price of $31.15 the day before ^[2].

Muscle preservation has become a crowded area of obesity research. Roche and Regeneron have each acquired obesity assets to pair with existing muscle drug candidates, and Eli Lilly signed a deal with Juvena Therapeutics focused on muscle health and body composition, according to the same report ^[2].

Why it matters for patients

Weight lost on GLP-1 and related drugs includes both fat and lean tissue, and how much of the loss comes from muscle has become a central question in obesity medicine ^[2]. This trial measured that split directly rather than estimating it.

Several limits are worth keeping in view. The results cover 24 weeks of treatment in a phase 2 study; whether the effect holds over a year or longer has not been reported ^[2]. Apitegromab is not approved for weight loss, or for any use, and no medicine is currently approved specifically to preserve muscle during weight-loss treatment ^[2].

Even in the group with the best result, lean mass loss was reduced, not eliminated: 14.6% of the weight lost still came from lean tissue ^[2]. And the combination did not produce more total weight loss than tirzepatide alone; it produced slightly less ^[2].

What happens next

The FDA is reviewing apitegromab for spinal muscular atrophy, with a decision expected by September ^[2]. Scholar Rock has not disclosed plans for a phase 3 trial of apitegromab in obesity ^[2]. Longer-term body-composition data from the EMBRAZE trial beyond the 24-week point have not been reported ^[2].