Monoclonal Antibody Shows Promise for Adjuvant Treatment of Spinal Muscular Atrophy

People with spinal muscular atrophy (SMA) who received treatment with apitegromab (Scholar Rock, Cambridge, MA) in addition to standard of care showed significant improvements in motor ability compared with those who received placebo. New safety and efficacy results from the phase 3 SAPPHIRE clinical trial (NCT05156320) were presented at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, demonstrating the potential of this investigational human monoclonal antibody (mAb) designed to inhibit myostatin activation to improve motor function in people with SMA.

SAPPHIRE was a randomized, double-blind, placebo-controlled phase 3 clinical trial that included 156 participants aged 2 to 12 years with SMA types 2 (SMA 2) and 3 (SMA 3) who were already receiving treatment with either Spinraza (nusinersen; Biogen, Cambridge, MA) or Evrysdi (risdiplam; Genentech, South San Francisco, CA): the standard of care for SMA. Participants were randomized 1:1:1 to receive intravenous infusions of either apitegromab 10 mg/kg, apitegromab 20 mg/kg, or placebo once every 4 weeks for a period of 12 months. The primary endpoint was change from baseline in physical ability as measured by total score of the Hammersmith Functional Motor Scale–Expanded (HFMSE). There was an additional exploratory population of 32 older participants aged 13 to 21 years who were randomized 2:1 to receive treatment with either apitegromab 20 mg/kg or placebo for 12 months.

• The primary endpoint was met, with a mean difference between the placebo (n=50) and apitegromab groups (n=106) of 1.8 points in change from baseline in total score on the HFMSE (P=.0192).
• There was a 1.4 point mean difference in change from baseline in HFMSE total score between participants who received apitegromab 20 mg/kg and those who received placebo.
• 30.4% of apitegromab-treated participants achieved a ≥3-point gain in HFMSE total score vs 12.5% in those who received placebo (nominal P=.0156).
• Participants who received apitegromab treatment showed consistent improvements across other motor function outcomes such as Revised Upper Limb Module (RULM) score and World Health Organization (WHO) motor milestones.
• Apitegromab treatment was shown to be well-tolerated with a safety profile consistent with previous study.
• No serious adverse events (SAEs) were related to apitegromab treatment.

“The findings from the SAPPHIRE trial are very exciting as they support the hypothesis that targeting muscle can provide functional improvement for patients with SMA on top of SMN-targeted therapy,” said Thomas O. Crawford, MD, Professor of Neurology and Pediatrics at Johns Hopkins University and Principal Investigator of the SAPPHIRE clinical trial. “Importantly, the improvements in function were observed consistently across multiple validated metrics used to assess patient functional outcomes in SAPPHIRE.”