Introduction: Muscular atrophy leads to functional motor loss in spinal muscular atrophy (SMA). Apitegromab, an investigational, fully human monoclonal antibody, inhibits signaling from pro- and latent forms of myostatin, directly increasing innervated muscle mass.
Methods: TOPAZ (NCT03921528), a multicenter, phase 2 study, evaluated the safety and efficacy of apitegromab in patients aged 2–21 years with Types 2 or 3 SMA. In the 52-week treatment period, 3 cohorts of patients received either 2- or 20-mg/kg apitegromab, alone (n=11) or in combination with nusinersen (n=47). Study completers could enroll in 3 sequential extension periods (52 weeks each), where all patients received 20-mg/kg apitegromab monthly. These analyses evaluate the effects of apitegromab in the nonambulatory patient population from the TOPAZ study (n=35) over 36 months. Muscle function was measured by the HFMSE, RULM, and WHO motor development milestones. Daily activities and mobility were evaluated by the PEDI-CAT and self-reported or caregiver proxy of perceived fatigue was assessed using the PROMIS Fatigue questionnaire.
Results: HFMSE and RULM showed sustained improvements throughout 36 months. Sustained improvements in PEDI-CAT domain scores and PROMIS perceived fatigue were also observed over 36 months. Analysis of WHO motor milestones showed achievement of new milestones. Results on patient-/caregiver-reported outcomes were consistent with improvements in motor function assessed by HFSME and RULM. The safety profile was consistent with previous reports.
Conclusions: Treatment with apitegromab was associated with sustained clinical benefit and improvements in patient- and caregiver-reported outcomes of function and perceived fatigue in patients with Types 2 or 3 SMA for 36 months. These results support further development of apitegromab in SMA.