Scholar Rock reports that its antibody preserves muscle during Zepbound treatment

A midstage clinical trial suggests it may be possible to lose weight on Zepbound while protecting more muscle. Scholar Rock announced on June 18, 2025, that its experimental antibody apitegromab, when added to tirzepatide (the active ingredient in Zepbound), shifted the makeup of weight loss toward fat and away from lean mass ^[2].

In the 24-week phase 2 study, called EMBRAZE, patients taking tirzepatide alone lost weight that was 30.2% lean mass. When patients added a 10 mg/kg dose of apitegromab to their tirzepatide regimen, that figure fell to 14.6% ^[2]. Put another way, the tirzepatide-plus-placebo group lost fat and lean mass in roughly a 70-to-30 split, while the apitegromab-tirzepatide group lost fat and lean mass in an 85-to-15 split ^[2].

There was a tradeoff. Total weight loss was slightly lower in the apitegromab group, at 12.3%, compared with 13.4% in the tirzepatide-plus-placebo group ^[2]. Scholar Rock described the combination as producing a "higher quality of weight loss" because more of the pounds lost came from fat rather than muscle ^[2]. The company said apitegromab was "generally well tolerated," with no serious adverse events or discontinuations tied to the drug ^[2].

Apitegromab is a myostatin inhibitor, a class of drug designed to block signals that trigger muscle breakdown. It is not yet approved for any use in the United States. The Food and Drug Administration is currently reviewing apitegromab for a different condition, spinal muscular atrophy, with a decision expected by September 2025, based on a phase 3 trial from October 2024 that showed a 1.8-point improvement in motor function compared with placebo after 52 weeks ^[2]. Scholar Rock's president of R&D, Akshay Vaishnaw, said the company remains focused on that SMA launch even as it explores the obesity findings ^[2]. Following the announcement, Scholar Rock's stock rose 5% in premarket trading to $32.80 ^[2].

Why it matters for patients

Loss of lean muscle mass is a known side effect of GLP-1 drugs like Zepbound, and researchers have flagged it as a health concern because muscle supports strength, metabolism, and physical function, especially in older adults ^[2]. If a drug like apitegromab can be shown to reduce that muscle loss without sacrificing much fat loss, it could eventually give patients on tirzepatide or similar medications another option to consider alongside their doctors. But this is early, phase 2 data in a combination that is not approved or available, so it says nothing about whether or when such a treatment might reach the market for weight loss.

The tradeoff seen in this trial, slightly less total weight loss in exchange for a better ratio of fat to muscle loss, is also worth noting. Whether that tradeoff would matter to a given patient is not something these results can answer, and longer-term data on function, safety, and durability are not yet available.

Scholar Rock is not alone in pursuing this angle. Roche and Regeneron have each acquired obesity drug candidates to pair with existing muscle-focused therapies, and Eli Lilly, which makes Zepbound, struck a deal with Juvena Therapeutics the week before this announcement aimed at improving muscle health and body composition during weight loss ^[2]. That suggests multiple companies see muscle preservation as an important unmet need in obesity treatment, though none of these approaches have reached late-stage testing or regulatory review for that use.

What happens next

The FDA is expected to decide on apitegromab for spinal muscular atrophy by September 2025 ^[2]. No timeline has been announced for further obesity-focused trials of apitegromab in combination with tirzepatide, and it is not yet known when or whether larger, longer studies will follow.