@article{b857f83fceaf472281310577a74a7fe8,
title = "Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study",
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.",
keywords = "Clinical trial, Neurofilament, Newborn screening, Nusinersen, Presymptomatic, Spinal muscular atrophy",
author = "{NURTURE Study Group} and {De Vivo}, {Darryl C.} and Enrico Bertini and Swoboda, {Kathryn J.} and Hwu, {Wuh Liang} and Crawford, {Thomas O.} and Finkel, {Richard S.} and Janbernd Kirschner and Kuntz, {Nancy L.} and Parsons, {Julie A.} and Ryan, {Monique M.} and Butterfield, {Russell J.} and Haluk Topaloglu and Tawfeg Ben-Omran and Sansone, {Valeria A.} and Jong, {Yuh Jyh} and Francy Shu and Staropoli, {John F.} and Douglas Kerr and Sandrock, {Alfred W.} and Christopher Stebbins and Marco Petrillo and Gabriel Braley and Kristina Johnson and Richard Foster and Sarah Gheuens and Ishir Bhan and Reyna, {Sandra P.} and Stephanie Fradette and Wildon Farwell",
note = "Funding Information: The authors thank the patients who are participating in this study and their parents/guardians and family members, without whom this effort cannot succeed. The authors also thank the people who are contributing to this study, including the study site principal investigators, clinical monitors, study coordinators, physical therapists, and laboratory technicians. Biogen provided funding for medical writing support in the development of this manuscript; Susan Chow, PhD, and Allison Green, PhD, from Excel Scientific Solutions wrote the first draft of the manuscript based on input from authors, and Nathaniel Hoover from Excel Scientific Solutions copyedited and styled the manuscript per journal requirements. The authors had full editorial control of the manuscript and provided their final approval of all content. Requests for data supporting this manuscript should be submitted to the Biogen Clinical Data Request Portal ( www.biogenclinicaldatarequest.com).",
year = "2019",
month = nov,
doi = "10.1016/j.nmd.2019.09.007",
language = "English (US)",
volume = "29",
pages = "842--856",
journal = "Neuromuscular Disorders",
issn = "0960-8966",
publisher = "Elsevier Limited",
number = "11",
}