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Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.
Neuromuscul Disord 2019; 29(11):842-856ND

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts.

Authors+Show Affiliations

Departments of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: dcd1@cumc.columbia.edu.Unit of Neuromuscular and Neurodegenerative Disorders, Post-Graduate Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy.Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.Departments of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Division of Neurology, Department of Pediatrics, Nemours Children's Hospital, Orlando, FL, USA.Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Neuropediatrics, University Medical Hospital, Bonn, Germany.Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.Royal Children's Hospital, University of Melbourne, Murdoch Children's Research Institute, Melbourne, Australia.Department of Pediatrics and Neurology, University of Utah, Salt Lake City, UT, USA.Department of Pediatric Neurology, Hacettepe University, Ankara, Turkey.Sidra Medicine, Department of Pediatrics, Qatar Foundation, Doha, Qatar; Division of Clinical and Metabolic Genetics, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.NEMO Clinical Center - NEuroMuscular Omniservice, Milan, Italy; Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University; Departments of Pediatrics and Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Maidenhead, Berkshire, UK.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.Biogen, Cambridge, MA, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31704158

Citation

De Vivo, Darryl C., et al. "Nusinersen Initiated in Infants During the Presymptomatic Stage of Spinal Muscular Atrophy: Interim Efficacy and Safety Results From the Phase 2 NURTURE Study." Neuromuscular Disorders : NMD, vol. 29, no. 11, 2019, pp. 842-856.
De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):842-856.
De Vivo, D. C., Bertini, E., Swoboda, K. J., Hwu, W. L., Crawford, T. O., Finkel, R. S., ... Farwell, W. (2019). Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscular Disorders : NMD, 29(11), pp. 842-856. doi:10.1016/j.nmd.2019.09.007.
De Vivo DC, et al. Nusinersen Initiated in Infants During the Presymptomatic Stage of Spinal Muscular Atrophy: Interim Efficacy and Safety Results From the Phase 2 NURTURE Study. Neuromuscul Disord. 2019;29(11):842-856. PubMed PMID: 31704158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. AU - De Vivo,Darryl C, AU - Bertini,Enrico, AU - Swoboda,Kathryn J, AU - Hwu,Wuh-Liang, AU - Crawford,Thomas O, AU - Finkel,Richard S, AU - Kirschner,Janbernd, AU - Kuntz,Nancy L, AU - Parsons,Julie A, AU - Ryan,Monique M, AU - Butterfield,Russell J, AU - Topaloglu,Haluk, AU - Ben-Omran,Tawfeg, AU - Sansone,Valeria A, AU - Jong,Yuh-Jyh, AU - Shu,Francy, AU - Staropoli,John F, AU - Kerr,Douglas, AU - Sandrock,Alfred W, AU - Stebbins,Christopher, AU - Petrillo,Marco, AU - Braley,Gabriel, AU - Johnson,Kristina, AU - Foster,Richard, AU - Gheuens,Sarah, AU - Bhan,Ishir, AU - Reyna,Sandra P, AU - Fradette,Stephanie, AU - Farwell,Wildon, AU - ,, Y1 - 2019/09/12/ PY - 2019/02/26/received PY - 2019/08/08/revised PY - 2019/09/09/accepted PY - 2019/11/11/pubmed PY - 2019/11/11/medline PY - 2019/11/10/entrez KW - Clinical trial KW - Neurofilament KW - Newborn screening KW - Nusinersen KW - Presymptomatic KW - Spinal muscular atrophy SP - 842 EP - 856 JF - Neuromuscular disorders : NMD JO - Neuromuscul. Disord. VL - 29 IS - 11 N2 - Spinal muscular atrophy (SMA) is a neurodegenerative disease associated with severe muscle atrophy and weakness in the limbs and trunk. We report interim efficacy and safety outcomes as of March 29, 2019 in 25 children with genetically diagnosed SMA who first received nusinersen in infancy while presymptomatic in the ongoing Phase 2, multisite, open-label, single-arm NURTURE trial. Fifteen children have two SMN2 copies and 10 have three SMN2 copies. At last visit, children were median (range) 34.8 [25.7-45.4] months of age and past the expected age of symptom onset for SMA Types I or II; all were alive and none required tracheostomy or permanent ventilation. Four (16%) participants with two SMN2 copies utilized respiratory support for ≥6 h/day for ≥7 consecutive days that was initiated during acute, reversible illnesses. All 25 participants achieved the ability to sit without support, 23/25 (92%) achieved walking with assistance, and 22/25 (88%) achieved walking independently. Eight infants had adverse events considered possibly related to nusinersen by the study investigators. These results, representing a median 2.9 years of follow up, emphasize the importance of proactive treatment with nusinersen immediately after establishing the genetic diagnosis of SMA in presymptomatic infants and emerging newborn screening efforts. SN - 1873-2364 UR - https://www.unboundmedicine.com/medline/citation/31704158/Nusinersen_initiated_in_infants_during_the_presymptomatic_stage_of_spinal_muscular_atrophy:_Interim_efficacy_and_safety_results_from_the_Phase_2_NURTURE_study L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-8966(19)31127-7 DB - PRIME DP - Unbound Medicine ER -