Clinical Report: FDA approves muscle-targeted SMA therapy

Overview

The FDA has approved apitegromab-mstn (Isembyld) for spinal muscular atrophy (SMA) in patients aged 2 years and older receiving SMN-targeted treatment. The approval is based on the SAPPHIRE trial, which demonstrated motor function improvements with apitegromab.

Background

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by motor neuron loss and muscle atrophy, leading to progressive disability. The introduction of targeted therapies has transformed the management of SMA. Apitegromab represents a novel approach by targeting muscle loss associated with the disease.

Data Highlights

Key Findings

• Apitegromab is approved for SMA in patients aged 2 years and older receiving SMN-targeted treatment.
• The SAPPHIRE trial showed a 2.2-point improvement on the Hammersmith Functional Motor Scale-Expanded (HFMSE) for patients receiving apitegromab 10 mg/kg.
• 34% of patients receiving apitegromab achieved an improvement of at least 3 points on the HFMSE compared to 14% in the placebo group.
• Common adverse reactions included upper respiratory tract infections, vomiting, and cough.
• Fractures occurred in 9% of patients receiving apitegromab 10 mg/kg versus 2% in the placebo group.

Clinical Implications

Monitoring for common adverse reactions and the potential risk of fractures is essential in patients receiving this therapy.

Conclusion

Apitegromab offers a new mechanism to address muscle loss in affected patients.

Related Resources & Content

1. Scholar Rock, FDA, 2026 -- FDA Approves First Therapy to Target Muscle Loss in Spinal Muscular Atrophy
2. ScienceDirect, 2025 -- Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE)
3. Neurology Clinical Practice, 2025 -- Spinal Muscular Atrophy Update in Best Practices
4. MDSpire News — FDA OKs First SMA Gene Replacement Therapy
5. MDSpire News — FDA Updates SMA Treatment Dosing
6. MDSpire News — FDA Approves Evrysdi Tablet for SMA Treatment
7. Brain — In utero therapy for spinal muscular atrophy: closer to clinical translation
8. FDA OKs First SMA Gene Replacement Therapy
9. FDA Updates SMA Treatment Dosing
10. FDA Approves Evrysdi Tablet for SMA Treatment
11. FDA Approves First Therapy to Target Muscle Loss in Spinal Muscular Atrophy | FDA
12. Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial - ScienceDirect
13. Spinal Muscular Atrophy Update in Best Practices | Neurology Clinical Practice