Spinal Muscular Atrophy
Apitegromab for spinal muscular atrophy (SMA)
Scholar Rock is the first company to show clinical proof of concept for a muscle-targeted treatment in spinal muscular atrophy (SMA). This treatment, called apitegromab, is an investigational therapy that has the potential to transform the standard of care for people living with SMA.
Apitegromab aims to help people with SMA improve their strength, function and endurance. Apitegromab is designed to selectively target latent, or upstream, myostatin—a protein growth factor that regulates muscle growth—to turn myostatin off before it is activated in a person’s muscle. The intent is to maintain or increase motor function for people currently being treated with existing SMA therapies that can slow further motor neuron degeneration but do not directly address muscle atrophy.
Our Pipeline
We have worked to turn our scientific discoveries into a pipeline of investigational therapies aimed at helping people with diseases where growth factors play a central role.
Scholar Rock reported positive topline data from the SAPPHIRE clinical trial in October 2024. Apitegromab is an investigational drug candidate under evaluation and has not been approved by any regulatory agency.
Myostatin: A Closer Look
Myostatin is a protein expressed primarily in skeletal muscle to negatively regulate muscle growth. When myostatin is activated, it works alongside other growth factors and hormones to maintain appropriate muscle mass. By selectively turning myostatin “off” and allowing muscle growth to occur, apitegromab treatment could potentially build muscle mass.
Another way to think about it is this: Apitegromab is designed to work like a wrench that can turn off the water supply (myostatin) before it ever reaches the kitchen sink (muscle). By “turning off” myostatin before it can be expressed, skeletal muscle cell growth has the potential to continue, which may improve muscle strength in a patient.
Advancing Apitegromab for SMA
Phase 2 TOPAZ Clinical Trial
The TOPAZ Phase 2 proof-of-concept trial investigated apitegromab in patients with Type 2 and Type 3 SMA over a 12-month treatment period. The findings from TOPAZ informed the design of SAPPHIRE, a randomized, double-blind, placebo-controlled, phase 3 clinical trial to further investigate apitegromab in non-ambulatory people with Type 2 and Type 3 SMA. Scholar Rock reported positive topline data from the SAPPHIRE clinical trial. The study achieved its primary endpoint demonstrating a statistically significant and clinically meaningful improvement for apitegromab versus placebo in motor function as measured by the gold standard HFMSE in SMA patients on chronic dosing of standard of care therapies (either nusinersen or risdiplam).
Phase 3 SAPPHIRE Clinical Trial
SAPPHIRE was a randomized, double-blind, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of apitegromab in non-ambulatory 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.
Phase 3 ONYX Clinical Trial
The ONYX open-label, multi-center extension study remains ongoing. The study is evaluating the long-term safety and efficacy of apitegromab in patients who completed the TOPAZ or SAPPHIRE trials.
Expanded Access Policy
As we advance investigational therapies through clinical development, our goal is to provide access to these therapies at the appropriate time and in the correct manner for patients.
