Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: results from the 36-month TOPAZ study
Por:
Crawford TO, Day JW, De Vivo DC, Krueger JM, Mercuri E, Nascimento-Osorio A, Pasternak A, Mazzone ES, Duong T, Song G, Marantz JL, Baver S, Yu D, Liu L and Darras BT
Publicada:
22 jul 2024
Resumen:
Background and purpose At 12 months in the phase 2 TOPAZ study, treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable safety profile. This manuscript reports the extended efficacy and safety in the nonambulatory group of the TOPAZ study at 36 months.Methods Patients who completed the primary study (NCT03921528) could enroll in an open-label extension, during which patients received apitegromab 20 mg/kg by intravenous infusion every 4 weeks. Patients were assessed periodically via the Hammersmith Functional Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM), World Health Organization (WHO) motor development milestones, Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) Daily Activities and Mobility domains, and Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire.Results Of the 58 patients enrolled in TOPAZ, 35 were nonambulatory (mean age 7.3 years). The mean change at 36 months in HFMSE score from baseline was +4.0 (standard deviation [SD]: 7.54), and + 2.4 (3.24) for RULM score (excluding n = 7 after scoliosis surgery). Caregiver-reported outcomes (PEDI-CAT and PROMIS Fatigue) showed improvements from baseline over 36 months. In addition, most patients (28/32) improved or maintained WHO motor milestones achieved at baseline. The most frequently reported treatment-emergent adverse events were pyrexia (48.6%), nasopharyngitis (45.7%), COVID-19 infection (40.0%), vomiting (40.0%), and upper respiratory tract infection (31.4%).Conclusion The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.
Filiaciones:
Crawford TO:
Johns Hopkins Medical, Baltimore, MD, United States
Day JW:
Stanford Neuroscience Health Center, Palo Alto, CA, United States
De Vivo DC:
Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, United States
Krueger JM:
Helen DeVos Children's Hospital, Grand Rapids, MI, United States
Mercuri E:
Centro Clinico NeMO, Fondazione Policlinico Gemelli, IRCCS, Rome, Italy
Pediatric Neurology and Psychiatry, Catholic University, Rome, Italy
Nascimento-Osorio A:
Neuromuscular Unit, Department of Neurology, Applied Research in Neuromuscular Diseases, Institut de Recerca Sant Joan de Déu (CIBERER), Barcelona, ISCIII, Esplugues de Llobregat, Spain
Pasternak A:
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
Mazzone ES:
Centro Clinico NeMO, Fondazione Policlinico Gemelli, IRCCS, Rome, Italy
Duong T:
Stanford Neuroscience Health Center, Palo Alto, CA, United States
Song G:
Scholar Rock, Inc., Cambridge, MA, United States
Marantz JL:
Scholar Rock, Inc., Cambridge, MA, United States
Baver S:
Scholar Rock, Inc., Cambridge, MA, United States
Yu D:
Scholar Rock, Inc., Cambridge, MA, United States
Liu L:
Scholar Rock, Inc., Cambridge, MA, United States
Darras BT:
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
Green Submitted, gold
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