Figure 3.

Higher dose of nusinersen is expected to lead to ~2.4‐fold increase in nusinersen levels in CSF compared with the approved 12‐mg dose. (A) Schematic illustrating higher‐dose regimen (two loading doses 2 weeks apart of 50 mg and maintenance dose 28 mg every 4 months) and the 12‐mg approved dose of nusinersen (four loading doses of 12 mg and maintenance dose 12 mg every 4 months). (B) Population PK model estimates steady‐state CSF concentration of nusinersen of 5 ng/mL with the 12‐mg approved dose of nusinersen and 12 ng/mL with the higher nusinersen dosing regimen. Steady state is predicted to be achieved after six maintenance doses, or 24 months after the final loading dose. Median values are shown; the confidence intervals for 12‐mg dose were previously described in MacCannell et al. ²⁰ Data for the higher dose will be obtained from the DEVOTE study. CSF = cerebrospinal fluid; D = day, PK = pharmacokinetic.