Risdiplam in types 2 and 3 spinal muscular atrophy: A randomised, placebo‐controlled, dose‐finding trial followed by 24 months of treatment

• DOI: 10.1111/ene.15499
• Publication Date: 2022-07-15T07:44:53Z
• Authors: Eugenio Mercuri; Giovanni Baranello; Odile Boespflug‐T...; Liesbeth De Waele; Nathalie Goemans; Janbernd Kirschner; Riccardo Masson; Elena S. Mazzone; Astrid Pechmann; Maria Carmela Pera; Carole Vuillerot; Silvia Bader‐Weder; Marianne Gerber; Ksenija Gorni; Janine Hoffart; Heidemarie Kletzl; Carmen Martin; Tammy McIver; Renata S. Scalco; Wai Yin Yeung; Laurent Servais
• Keywords: SMN1; Tolerability; Pharmacodynamics

Abstract Background and purpose Spinal muscular atrophy (SMA) is caused by reduced levels of survival motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam an orally administered molecule that modifies SMN2 pre‐mRNA splicing increase functional SMN protein. Methods SUNFISH Part 1 was a dose‐finding study conducted 51 individuals with types 2 3 SMA aged 2–25 years. A dose‐escalation method used identify appropriate dose for subsequent pivotal 2. Individuals were randomized (2:1) risdiplam or placebo at escalating minimum 12‐week, double‐blind, placebo‐controlled period, followed treatment 24 months. The selection based on safety, tolerability, pharmacokinetic, pharmacodynamic data. Exploratory efficacy also measured. Results There no difference safety findings all assessed levels. dose‐dependent blood observed; median twofold obtained within 4 weeks initiation highest level. sustained over months treatment. showed improvement stabilization function. selected 5 mg patients body weight ≥20 kg 0.25 mg/kg <20 kg. Conclusions demonstrated after risdiplam. observed profile supported study. long‐term are being ongoing