Scientific rationale for a higher dose of nusinersen.

ABSTRACT:

Objective

The long-term favorable safety profile of nusinersen provides an opportunity to consider a higher dose. We report on the relationships between nusinersen cerebrospinal fluid (CSF) exposure, biomarker levels, and clinical efficacy.

Methods

The analyses used data from the CS3A and ENDEAR studies of nusinersen in participants with infantile-onset spinal muscular atrophy (SMA). Steady-state CSF trough (C_trough ) levels, plasma phosphorylated neurofilament heavy chain (pNF-H) levels, body weight, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores were selected as parameters of interest. A validated population pharmacokinetic (PK) model was applied to predict the nusinersen CSF C_trough . PK/pharmacody

SUBMITTER: Finkel RS 

PROVIDER: S-EPMC9186144 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature