Spinal Muscular Atrophy
Apitegromab for
spinal muscular
atrophy (SMA)
We are investigating apitegromab, a muscle-targeted therapy with the aim of improving motor function for people living with SMA who have been treated with certain existing SMA therapies. Scholar Rock is the first company to show clinical proof-of-concept for an investigational muscle-targeted therapy in SMA.
Despite significant advances in SMA treatments, progressive muscle weakness continues to be a hallmark of the disease. Existing treatments do not directly address the muscular components, including muscle atrophy and weakness that can lead to deterioration in mobility, swallowing, and breathing and cause excess fatigue and exhaustion.
Strong clinical and preclinical evidence indicates that apitegromab has the potential to improve motor function while minimizing adverse effects. If ongoing trials are successful and apitegromab is approved, it could open a number of potential benefits above existing SMA treatments—such as sustained or improved motor function intended to provide better quality of life for those living with SMA.
Apitegromab is a selective inhibitor of latent myostatin. Myostatin is a protein expressed primarily in skeletal muscle that regulates muscle mass. When myostatin is activated, it works with other growth factors and hormones to inhibit muscle growth. Unlike most myostatin inhibitors, apitegromab selectively targets the latent, or inactive, form of myostatin to block its activation in the muscle.
Clinical Trials
SAPPHIRE
SAPPHIRE was a randomized, double-blind, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of apitegromab in nonambulatory patients with Types 2 and 3 SMA who are receiving current standard of care (either nusinersen or risdiplam). SAPPHIRE enrolled 156 patients aged 2-12 years old in the main efficacy population. These patients were randomized 1:1:1 to receive for 12 months either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo by intravenous (IV) infusion every 4 weeks. An exploratory population that enrolled 32 patients aged 13-21 years old was also evaluated. These patients were randomized 2:1 to receive either apitegromab 20 mg/kg or placebo.
TOPAZ
TOPAZ was a Phase 2 proof-of-concept trial that assessed the safety and efficacy of apitegromab in patients with Type 2 and Type 3 SMA. Topline 12-month results were shared in April 2021 with subsequent data read outs, including 24-, 36- and 48-month extension data that reinforced long-term substantial and sustained improvement of motor function with no new safety findings.
