Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam

Summary

This Phase 3 trial (Study SRK-015-003) was conducted in patients ≥2 years old at Screening, who were previously diagnosed with later-onset spinal muscular atrophy (SMA) (i.e., Type 2 and Type 3 SMA) and were receiving an approved survival motor neuron (SMN) upregulator therapy (i.e., either nusinersen or risdiplam), to confirm the efficacy and safety of apitegromab as an adjunctive therapy to nusinersen and evaluate the efficacy and safety of apitegromab as an adjunctive therapy to risdiplam.

Timeline

Start

2022-04-14

Primary completion

2024-12-18

Completion

2024-12-18

Outcome

Met primary endpoint

paper 1·8 (95% CI 0·30 to 3·32, p=0·019) points for participants aged 2-12 years receiving apitegromab versus placebo PMID 40818473 ↗

release “Reported positive topline data from Phase 3 SAPPHIRE clinical trial . The study achieved its primary endpoint” scholarrock.com ↗

release “The SAPPHIRE trial met its primary endpoint for the main efficacy population” scholarrock.com ↗

release “The SAPPHIRE trial met its primary endpoint for the main efficacy population with a statistically significant 1.8-point improvement” scholarrock.com ↗

release “As reported, the Phase 3 SAPPHIRE trial met its primary endpoint, achieving a statistically significant and clinically meaningful improvement in motor function” scholarrock.com ↗

Publications

• Crawford TO, Servais L, Mercuri E, Kolbel H, Kuntz N, Finkel RS, Krueger J, Batley K, Young SD, Marantz JL, Song G, Yao B, Zhao G, Rossello J, Tirucherai GS, Mazzone ES, Butterfield RJ, de la Banda MGG, Seferian AM, Sansone VA, De Waele L, van der Pol WL, Cances C, Pechmann A, Darras BT; SAPPHIRE Study Group. 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. Lancet Neurol. 2025 Sep;24(9):727-739. doi: 10.1016/S1474-4422(25)00225-X.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Apitegromab	Monoclonal antibody	10 mg/kg	Intravenous
Subject	Apitegromab	Monoclonal antibody	20 mg/kg	Intravenous

Indications