Apitegromab is an investigational, fully human, monoclonal antibody that specifically binds to pro- and latent- forms of myostatin, an inhibitor of muscle growth and strength, thereby inhibiting myostatin activation. TOPAZ is a phase 2, 3-cohort study (NCT03921528) of Types 2/3 SMA patients dosed with IV apitegromab Q4W for 12-months and in subsequent 12-month extension periods. In the nonambulatory Type 2 SMA cohort (nusinersen started before age 5; n=20) patients on nusinersen were randomized in a blinded manner to receive 2 or 20mg/kg apitegromab for the first 12-month treatment period. During the first extension period, patients initially assigned to the 2mg/kg dose were switched over to the 20mg/kg dose. In a separate nonambulatory Type 2/3 cohort (nusinersen started at age > 5; n=15), patients on nusinersen received 20mg/kg apitegromab. In these 2 nonambulatory cohorts, 46% of patients achieved ≥3 point change in HFMSE and 50% achieved ≥2 point change in RULM at 24-months. _x000D_
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Patient reported outcomes that measure fatigue, endurance and impacts to activities of daily living were assessed by PEDICAT and PROMIS measures in the TOPAZ study. We will present analyses of fatiguability and ADL improvements and their consistency with increases in motor function scales in the nonambulatory cohorts. The patient populations, including exploratory analyses (e.g., age, mobility, weight) will be considered together with motor function scales and patient reported outcomes over 24 months._x000D_
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Incidence and severity of AEs were consistent with the underlying patient population and nusinersen therapy throughout the 24-month treatment period with no safety risks identified to date._x000D_
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Apitegromab has the potential to be the first muscle-targeted therapy to address motor function impairment affecting patients with SMA and further exploration of its impact on Quality of Life (QoL) is warranted