The US Food and Drug Administration (FDA) has approved Isembyld (apitegromab-mstn) for the treatment of spinal muscular atrophy (SMA) in patients ages 2 years and older who are currently receiving a survival motor neuron 2 (SMN2)-targeted treatment.
SMA is a genetic neuromuscular disorder characterized by the loss of motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. SMA mainly affects the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses. SMA is caused by genetic mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA, with type 1 being the most severe and type 4 the least severe.
Apitegromab is a fully human monoclonal IgG4 antibody that binds to promyostatin and latent myostatin and inhibits the activation of myostatin, blocking myostatin signaling. Myostatin is a negative regulator of skeletal muscle growth. The approval was based on positive results from the phase 3 pivotal, randomized, double-blind, placebo-controlled SAPPHIRE clinical trial (NCT05156320).
The study met its primary endpoint, and demonstrated a robust, clinically meaningful 2.2-point improvement in the Hammersmith Functional Motor Scale-Expanded (HFMSE) in patients receiving apitegromab 10 mg/kg and an SMN2-targeted treatment compared to patients receiving an SMN2-targeted treatment alone at one year. Additionally, 34.2% of apitegromab-treated patients showed a 3-point or greater increase in HFMSE compared to 13.5% of placebo-treated patients.
Additionally, apitegromab was well-tolerated. In the SAPPHIRE study, the most common adverse reactions were upper respiratory tract infections, vomiting, cough, other viral infections, headache, gastroenteritis, pharyngitis, and hypersensitivity. Fractures occurred in 9% of patients treated with apitegromab 10 mg/kg versus 2% in placebo.
With the approval of apitegromab, Scholar Rock was awarded a Rare Pediatric Disease Priority Review Voucher, which may be used to obtain priority review for a future marketing application.
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To learn more about SMA and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/