Phase III SPR1NT and STR1VE-EU trials show efficacy in spinal muscular atrophy.- Novartis

New late-breaker data from the completed two-copy cohort of the Phase III SPR1NT clinical trial demonstrate age-appropriate milestone development in presymptomatic children with SMA without respiratory or nutritional support of any kind, and with no serious, treatment-related adverse events. One hundred percent of patients (14/14) met the secondary endpoint of survival without ventilatory support of any kind at 14 months of age, versus only 26 percent of patients in the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. All patients (100 percent) achieved the primary endpoint of sitting independently for at least 30 seconds, including 11 (79 percent) who achieved this milestone within the WHO window of normal development. Eleven patients (79 percent) could stand independently, seven of whom achieved this milestone within the WHO window of normal development. Nine patients (64 percent) could walk independently, five of whom achieved this milestone within the WHO window of normal development.

The completed Phase III STR1VE-EU trial demonstrated rapid improvements in motor function following treatment with Zolgensma, and the majority of patients achieved motor milestones not observed in the natural history of SMA Type 1. Thirty-three patients were enrolled; and 32 patients completed the study. Twenty-seven of 33 patients (82 percent) achieved developmental motor milestones not observed in the natural history of SMA Type 1. Fourteen of 32 patients (44 percent) in the intention-to-treat (ITT) population achieved the primary endpoint of sitting independently for at least 10 seconds, observed at a median age of 15.9 months (7.7–18.6). The patient who was not in the ITT population also achieved this primary outcome measure. Twenty-three of 30 patients (77 percent) achieved head control (three already had control at baseline), 19 of 33 (58 percent) rolled from back to sides and 16 patients (49 percent) sat without support for at least 30 seconds, including all patients who met the primary endpoint of sitting without support for at least 10 seconds. In addition, two patients stood with assistance, and one crawled, stood, pulled to stand, and walked without assistance, all by 18 months of age. Safety remained consistent with previously reported data.

The Zolgensma data represent a significant contrast to the natural history of SMA Type 1, which leads to progressive and irreversible loss of motor function and if left untreated, often death or permanent ventilation by the age of two years. Remarkably, all children (100 percent) treated presymptomatically in the SPR1NT two-copy cohort achieved event-free survival, were independent of respiratory and nutritional support. Among symptomatic children with SMA Type 1 treated in the STR1VE-EU trial, including patients with more severe disease at baseline, the majority of children (82 percent) achieved developmental motor milestones not observed in the natural history of SMA Type 1, including 16 children (49 percent) who sat without support for at least 30 seconds. The data will be presented at the European Academy for Neurology (EAN) Virtual Congress 2021.