Skip to main content

ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neuromuscular Disorders and Peripheral Neuropathies
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1419791

Long-term efficacy, safety, and patient-reported outcomes of apitegromab in patients with spinal muscular atrophy: Results from the 36-month TOPAZ study

Provisionally accepted
Thomas Crawford Thomas Crawford 1John W. Day John W. Day 2*Darryl C. De Vivo Darryl C. De Vivo 3*Jena M. Krueger Jena M. Krueger 4*Eugenio Mercuri Eugenio Mercuri 5,6Andres Nascimento Andres Nascimento 7*Amy Pasternak Amy Pasternak 8*ELENA S. MAZZONE ELENA S. MAZZONE 5Tina Duong Tina Duong 2Gouchen Song Gouchen Song 9*Jing L. Marantz Jing L. Marantz 9*Scott Baver Scott Baver 9*Dongzi Yu Dongzi Yu 9*Lan Liu Lan Liu 9*Basil T. Darras Basil T. Darras 8
  • 1 Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States
  • 2 Stanford Neuroscience Health Center, Stanford Healthcare, Palo Alto, California, United States
  • 3 Columbia University Irving Medical Center, Columbia University, New York, New York, United States
  • 4 Helen DeVos Children's Hospital, Grand Rapids, Michigan, United States
  • 5 Agostino Gemelli University Polyclinic (IRCCS), Rome, Lazio, Italy
  • 6 Catholic University, Rome, Italy
  • 7 Sant Joan de Déu Research Institute (IRSJD), Esplugues de Llobregat, Spain
  • 8 Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 9 Scholar Rock, Cambridge, Maryland, United States

The final, formatted version of the article will be published soon.

    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.: 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%).The benefit of apitegromab treatment observed at 12 months was sustained at 36 months with no new safety findings.

    Keywords: apitegromab, Caregiver-reported outcomes, efficacy, Long-term, Motor function, Safety, spinal muscular atrophy

    Received: 18 Apr 2024; Accepted: 08 Jul 2024.

    Copyright: © 2024 Crawford, Day, De Vivo, Krueger, Mercuri, Nascimento, Pasternak, MAZZONE, Duong, Song, Marantz, Baver, Yu, Liu and Darras. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    John W. Day, Stanford Neuroscience Health Center, Stanford Healthcare, Palo Alto, 94304, California, United States
    Darryl C. De Vivo, Columbia University Irving Medical Center, Columbia University, New York, NY 10027, New York, United States
    Jena M. Krueger, Helen DeVos Children's Hospital, Grand Rapids, MI 49503, Michigan, United States
    Andres Nascimento, Sant Joan de Déu Research Institute (IRSJD), Esplugues de Llobregat, 08950, Spain
    Amy Pasternak, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, United States
    Gouchen Song, Scholar Rock, Cambridge, 02139, Maryland, United States
    Jing L. Marantz, Scholar Rock, Cambridge, 02139, Maryland, United States
    Scott Baver, Scholar Rock, Cambridge, 02139, Maryland, United States
    Dongzi Yu, Scholar Rock, Cambridge, 02139, Maryland, United States
    Lan Liu, Scholar Rock, Cambridge, 02139, Maryland, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.