Scholar Rock announced positive results from its Phase 2 EMBRAZE trial, demonstrating that apitegromab significantly preserved lean muscle mass in patients receiving tirzepatide for weight loss. The study showed that patients receiving apitegromab with tirzepatide preserved 54.9% more lean mass compared to those receiving tirzepatide alone, representing an additional 4.2 pounds of lean mass preservation (p=0.001).
Trial Results Show Superior Weight Loss Quality
The 24-week randomized, double-blind, placebo-controlled trial enrolled 100 subjects aged 18-65 with obesity (BMI ≥30.0 kg/m²) or overweight (BMI ≥27.0 kg/m² with weight-related comorbidities). Patients were randomized 1:1 to receive either apitegromab 10mg/kg or placebo by intravenous infusion every four weeks, with all participants receiving tirzepatide.
The combination therapy demonstrated markedly improved weight loss composition. Patients receiving apitegromab with tirzepatide achieved weight loss consisting of 85% fat mass and 15% lean mass, compared to tirzepatide alone which resulted in 70% fat mass and 30% lean mass loss. While both groups achieved substantial weight reduction - 12.3% for the combination versus 13.4% for tirzepatide alone - the quality of weight loss was significantly enhanced with apitegromab.
"GLP therapies have been an effective and important innovation for individuals living with obesity and cardiometabolic disorders; however, these treatments can result in substantial loss of lean muscle mass for patients, leading to unwanted health risks," said Akshay Vaishnaw, M.D., Ph.D., President of R&D at Scholar Rock.
Addressing Muscle Loss Concerns with GLP-1 Therapies
The trial addressed growing concerns about lean mass loss associated with GLP-1 receptor agonists. The study revealed that 30% of total weight loss with tirzepatide alone was due to lean mass loss, highlighting a significant clinical concern. Patients on tirzepatide alone lost 17.7 pounds of fat mass, while those receiving the combination lost 18.8 pounds of fat mass, demonstrating that muscle preservation did not compromise fat loss effectiveness.
Safety Profile Remains Favorable
Apitegromab maintained its established safety profile in the obesity setting. The incidence of adverse events was generally similar between apitegromab and placebo groups, with observed adverse events consistent with tirzepatide's known safety profile. No subjects experienced serious adverse events or discontinuations related to apitegromab treatment, and there were no deaths reported during the study period.
Myostatin Inhibition Mechanism
Apitegromab is a fully human monoclonal antibody that inhibits myostatin activation by selectively binding the pro- and latent forms of myostatin in skeletal muscle. Myostatin, a member of the TGF-β superfamily of growth factors, is expressed primarily by skeletal muscle cells, and its absence is associated with increased muscle mass and strength across multiple animal species, including humans.
Strategic Focus Remains on Neuromuscular Diseases
Despite the encouraging obesity trial results, Scholar Rock emphasized its continued focus on apitegromab's development for spinal muscular atrophy (SMA), where it has demonstrated clinical success in a pivotal Phase 3 trial. The FDA has granted Fast Track, Orphan Drug, and Rare Pediatric Disease designations for apitegromab in SMA treatment.
"We are pleased that the EMBRAZE trial accomplished its objective by achieving its primary endpoint. The results validated our hypothesis that our platform of highly selective myostatin inhibitors has the potential to support healthier weight loss for millions of patients on GLP therapies," Vaishnaw stated.
The company is also advancing SRK-439, a subcutaneous anti-myostatin antibody, with plans to file an IND application in the second half of this year for first-in-human studies targeting various neuromuscular disorders.
