Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study

• Published in: Neuromuscular disorders : NMD Vol. 29; no. 11; pp. 842 - 856
• Main Authors: De Vivo, Darryl C., Bertini, Enrico, Swoboda, Kathryn J., Hwu, Wuh-Liang, Crawford, Thomas O., Finkel, Richard S., Kirschner, Janbernd, Kuntz, Nancy L., Parsons, Julie A., Ryan, Monique M., Butterfield, Russell J., Topaloglu, Haluk, Ben-Omran, Tawfeg, Sansone, Valeria A., Jong, Yuh-Jyh, Shu, Francy, Staropoli, John F., Kerr, Douglas, Sandrock, Alfred W., Stebbins, Christopher, Petrillo, Marco, Braley, Gabriel, Johnson, Kristina, Foster, Richard, Gheuens, Sarah, Bhan, Ishir, Reyna, Sandra P., Fradette, Stephanie, Farwell, Wildon
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01-11-2019; The Authors. Published by Elsevier B.V
• Subjects: Child, Preschool; Clinical trial; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Motor Activity; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - physiopathology; Muscular Atrophy, Spinal - therapy; Neurofilament; Newborn screening; Nusinersen; Oligonucleotides - administration & dosage; Oligonucleotides - adverse effects; Presymptomatic; Spinal muscular atrophy; Survival of Motor Neuron 2 Protein - genetics; Time Factors; Treatment Outcome; Newborn screening; Nusinersen; Presymptomatic; Clinical trial; Neurofilament; Spinal muscular atrophy
• ISSN: 0960-8966; 1873-2364; 1873-2364
• DOI: 10.1016/j.nmd.2019.09.007

•NURTURE is an ongoing study of nusinersen started in a presymptomatic stage of SMA.•All infants were ≥25 months old, and alive without permanent ventilation.•All infants achieved independent sitting and 88% (22/25) were walking alone.•Nusinersen demonstrated durability of effect with a median 2.9 years of follow up.•Nusinersen was well tolerated with no new safety concerns over extended follow up.
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.