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.
Pechmann, Astrid | Baumann, Matthias | Bernert, Günther | Flotats-Bastardas, Marina | Gruber-Sedlmayr, Ursula | von der Hagen, Maja | Hasselmann, Oswald | Hobbiebrunken, Elke | Horber, Veronka | Johannsen, Jessika | Kellersmann, Anna | Köhler, Cornelia | von Moers, Arpad | Müller-Felber, Wolfgang | Plecko, Barbara | Reihle, Christof | Schlachter, Kurt | Schreiber, Gudrun | Schwartz, Oliver | Smitka, Martin | Steiner, Elisabeth | Stoltenburg, Corinna | Stüve, Burkhard | Theophil, Manuela | Weiß, Claudia | Wiegand, Gert | Wilichowski, Ekkehard | Winter, Benedikt | Wittmann, Wolfgang | Schara, Ulrike | Kirschner, Janbernd Treatment with Nusinersen – Challenges Regarding the Indication for Children with SMA Type 1. Journal of Neuromuscular Diseases. In press.
The natural history of patients with spinal muscular atrophy (SMA) has changed due to advances in standard care and development of targeted treatments. Nusinersen was the first drug approved for the treatment of all SMA patients. The transfer of clinical trial data into a real-life environment is challenging, especially regarding the advice of patients and families to what extent they can expect a benefit from the novel treatment. We report the results of a modified Delphi consensus process among child neurologists from Germany, Austria and Switzerland about the indication or continuation of nusinersen treatment in children with SMA type 1 based on different clinical case scenarios.
Pechmann et al. Courtesy of ResearchGate