Scholar Rock has published pivotal Phase 3 data in The Lancet Neurology demonstrating that apitegromab—a first-in-class muscle-targeted therapy—delivers clinically meaningful motor function improvements in children and adults with spinal muscular atrophy (SMA) receiving SMN-targeted treatment.
Study design and population
The SAPPHIRE trial enrolled 188 nonambulatory patients aged 2–21 with Type 2 or 3 SMA, all receiving either nusinersen or risdiplam. Participants were randomised to receive apitegromab (10 or 20 mg/kg) or placebo via monthly intravenous infusion over 52 weeks.
Motor function outcomes
The primary endpoint was improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE). Apitegromab achieved a statistically significant mean improvement of 1.8 points (p=0.019) over placebo in the 2–12-year-old efficacy population. Key findings included:
- 30.4% of apitegromab-treated patients achieved ≥3-point HFMSE improvement vs. 12.5% on placebo
- 19.6% achieved ≥4-point improvement vs. 6.3% on placebo
Consistent benefits were observed across age groups, treatment types, and geographic regions.
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Safety and regulatory status
Apitegromab was well tolerated across all age groups, with no new safety signals. The safety profile aligned with previous Phase 2 TOPAZ data. The FDA has accepted the Biologics License Application under priority review, with a target decision date of 22 September 2025. EMA review is also underway, with commercial launch anticipated in 2025 (US) and 2026 (EU).
Mechanism of action
Apitegromab is a monoclonal antibody that inhibits myostatin activation by selectively binding its pro- and latent forms in skeletal muscle. This approach targets muscle weakness directly, complementing existing SMN-preserving therapies.
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