Evaluation of Nusinersen on Impact of Caregiver Experience and HRQOL in Later-onset Spinal Muscular Atrophy (SMA): Results from the Phase 3 CHERISH Trial (1429)

Objective: The objective of this study was to compare health-related quality of life (HRQoL) from the Phase 3 CHERISH trial among nusinersen vs. sham-controlled patients. Background: SMA is a rare genetic disease characterized by degeneration of motor neurons resulting in progressive muscular weakness and atrophy. Limited data exists on the impact of SMA therapies on HRQoL. Design/Methods: Data from CHERISH, a randomized, double-blind, multicenter, sham-controlled clinical trial of later-onset SMA (most likely to develop SMA Type II or III) were analyzed. The exploratory endpoint of HRQoL was assessed using both the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) administered at screening and Days 169 (Month 6) and 456 (Month 15), and the Pediatric Quality of Life Inventory (PedsQL), administered at several timepoints from screening to Month 15. ANCOVA modeling was used to analyze least squares (LS) mean change from baseline through Month 15. Results: The impact for caregivers was reduced in three out of seven domains of the ACEND in the nusinersen group at Months 6 and 15; feeding/grooming/dressing, transfer, and mobility. The impact on caregivers was increased in these domains for the sham group at both assessments. The greatest reduction for caregivers was in the mobility domain: LS mean difference (95%) from baseline to Month 15 of nusinersen vs. sham was 11.9 (3.9, 19.8). Continued reductions in the impact of caregivers were found with longer time on nusinersen vs. sham in many domains. Results also showed improvements in PedsQL for nusinersen vs. sham for both patient and parent assessments. For example, the LS mean difference for nusinersen vs. sham from baseline to Month 15 was 5.0 (0.7, 9.3) for the parent assessment. Conclusions: Treatment with nusinersen was associated with reducing the impact on caregivers and improvements in HRQoL over sham control in later-onset SMA patients. Study Supported by: Biogen Disclosure: Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Johnson holds stock and/or stock options in Biogen. Dr. Paradis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Paradis holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Naoshy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Naoshy holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Wong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Montes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory boards for Biogen, Cytokinetics, Roche, Scholar Rock, and SMA Foundation; consultant for Biogen and Ionis Pharmaceuticals, Inc.; research support from Eunice Kennedy Shriver National Institute for Child Health and Human Development and Muscular D. Dr. Montes has received research support from Research support from Eunice Kennedy Shriver National Institute for Child Health and Human Development and Muscular Dystrophy Association. Dr. Krasinski has nothing to disclose.