The phase 2/3 DEVOTE study investigated high-dose nusinersen (50/28 mg) in patients with spinal muscular atrophy (SMA).[1][2] In untreated infants with infantile-onset SMA, the high dose resulted in a statistically significant improvement in motor function as measured by the CHOP-INTEND score of 15.1 points versus −11.1 points in the sham control group (difference 26.19 points; p<0.0001) by day 183.[1][2] Compared with the standard dose of 12 mg, a 29.9% higher risk of event-free survival was achieved (HR 0.701; p=0.2775).[1] In patients with later onset SMA, the high dose showed numerically greater improvements on the HFMSE and RULM scales compared to the 12 mg dose.[1][2] In part C of the study, patients switching from the 12 mg dose to 50/28 mg showed a mean improvement of 1.8 points on the HFMSE and 1.2 points on the RULM by day 302.[2][6] The high dose reduced plasma neurofilament levels more rapidly, indicating a slowing of neurodegeneration.[3][6] The treatment was generally well tolerated with no new safety issues.[1][2]