Apitegromab–tirzepatide combo reduces lean mass loss in obesity patients, providing a new edge in weight loss drug development
In a promising development for the obesity drug market, Scholar Rock’s investigational SMA treatment apitegromab has shown potential to help Zepbound (tirzepatide) patients preserve lean muscle mass during weight loss. These findings from a Phase 2 clinical trial suggest a new therapeutic opportunity beyond spinal muscular atrophy (SMA).
According to Scholar Rock’s press release dated June 18, the combination of apitegromab (10 mg/kg) with Eli Lilly’s Zepbound (tirzepatide) led to a 50% reduction in lean mass loss over 24 weeks. Patients on the combination therapy lost only 14.6% lean mass versus 30.2% with tirzepatide alone, while maintaining similar overall weight loss levels.
Apitegromab-Tirzepatide Yields Higher Quality Weight Loss
The study highlighted a shift in body composition quality. In the apitegromab-tirzepatide group, 85% of weight loss came from fat and just 15% from lean mass, compared to a 70/30 fat-to-lean ratio in the tirzepatide-placebo group.
- Weight loss outcomes were comparable:
- 12.3% weight loss for apitegromab-tirzepatide
- 13.4% weight loss for tirzepatide-placebo
Importantly, apitegromab was well-tolerated. No severe adverse events or treatment discontinuations were reported in the trial.
Apitegromab is currently under FDA review for spinal muscular atrophy (SMA), with a decision expected by September 2025. The filing follows a successful Phase 3 trial in October 2024, which showed a 1.8-point motor function improvement over placebo after 52 weeks.
While SMA remains the primary indication, Scholar Rock believes that preserving muscle mass during GLP-1 receptor agonist therapy like Zepbound could open the door to broader applications in obesity care.
“GLP-1 therapies are transformative for obesity and cardiometabolic health, but the associated loss of lean body mass raises health concerns,” said Akshay Vaishnaw, President of R&D at Scholar Rock.
“The EMBRAZE trial supports our hypothesis that selective myostatin inhibition can help patients maintain healthier weight loss profiles.”
As biopharma giants like Roche, Regeneron, and Lilly invest heavily in muscle health and body composition therapies, Scholar Rock’s early success with apitegromab positions it as a potential leader in the next phase of obesity drug innovation.
