Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA). Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6). We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14. Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.

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Competing interests: LM has received honoraria for speaking and compensation for congress participations from: Sanofi Genzyme and Biogen. LB reports speaker honoraria from PTC Therapeutics, participation in advisory boards for PTC Therapeutics and Sarepta Therapeutics and participation in research sponsored by Santhera Pharmaceuticals. SB received funds for travel and congress participation from Sanofi Genzyme and Biogen. LP has received compensation for congress participations from: Sanofi Genzyme and Biogen. MG received honoraria for speaking and grants to attend scientific meetings from Sanofi-Genzyme and Pfizer. VB compensation for congress participations from Biogen and Sanofi Genzyme. LC received compensation for congress participations from Biogen. RP has received compensation for congress participation from Sanofi Genzyme and Biogen. RT has received compensation for congress participations from Sanofi Genzyme, Biogen and Roche. ES has received compensation for congress participations from: Biogen. GR has received compensation for congress participations from Sanofi Genzyme, CSL Behring, Santhera and Biogen. RZ has received funds for travel and congress participation from Biogen. MS has received speaker’s honoraria from ITALFARMACO, PIAM, Boheringer and Novartis Pharmaceuticals. LP received compensation for congress participations from Biogen Inc, Italy. AS received honoraria for speaking and grants to attend scientific meetings from Sanofi-Genzyme, Alnylam Pharmaceuticals, Akcea Therapeutics and Pfizer. LV has received compensation for congress participation from Sanofi Genzyme and Biogen. RM received compensation for participating on advisory boards in relation to MG clinical trial design, congress participations and research support in the last 5 years from: Catalyst Pharmaceuticals, Alexion Pharmaceuticals, ARGENX Pharma, Biomarin. RL has received: Lecture fees from LT3 s.r.l., NICO s.r.l., SUMMEET s.r.l. and GALEN SYMPOSION s.r.o.; fees for consultancy (Advisory Board) from LT3 s.r.l. and PREX s.r.l.; fees for scientific meeting organization from I & C s.r.l.; Chair meeting fees from PLANNING CONGRESSI s.r.l. GC in the last two years has received compensation for advisory board compensation from: Sanofi Genzyme, Spark, Roche, Lupin and Santhera, congress participations from: Sanofi Genzyme, CSL Behring, Sarepta and Biogen. ILS received compensation for congress participation from Biogen, Italy. TM has received compensation for Scientific Board participations from Sanofi Genzyme; for congress participation from Biogen. GC received compensation for participation ad advisory board for Roche, Sarepta and Italfarmaco. EP reports personal fees from Sarepta, grants and non-financial support from Santhera, personal fees and non-financial support from PTC Pharmaceuticals, non-financial support from Genzyme, personal fees from Roche, outside the submitted work.