A Semi‐Mechanistic Population Pharmacokinetic Model of Nusinersen: An Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 7; no. 9; pp. 581 - 592
• Main Authors: Biliouris, Konstantinos, Gaitonde, Puneet, Yin, Wei, Norris, Daniel A., Wang, Yanfeng, Henry, Scott, Fey, Robert, Nestorov, Ivan, Schmidt, Stephan, Rogge, Mark, Lesko, Lawrence J., Trame, Mirjam N.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2018; John Wiley and Sons Inc; Wiley
• Subjects: Age; Atrophy; Brain research; Clinical trials; Drug dosages; Employees; Gene expression; Hybridization; Life expectancy; Musculoskeletal system; Neuromuscular diseases; Patients; Pediatrics; Pharmacokinetics; Plasma; Proteins; Sensitivity analysis; Spinal cord; Studies

A pharmacokinetic (PK) model was developed for nusinersen, an antisense oligonucleotide (ASO) that is the first approved treatment for spinal muscular atrophy (SMA). The model was built with data from 92 nonhuman primates (NHPs) following intrathecal doses (0.3–7 mg) and characterized the PK in cere...