2023 American Academy of Neurology Abstract Website

Laurent Servais¹, Maryam Oskoui², John Day³, Nicholas Deconinck⁴, Elena Mazzone⁵, Andrés Nascimento⁶, Kyoko Saito⁷, Carole Vuillerot⁸, Giovanni Baranello⁹, Odile Boespflug-Tanguy¹⁰, Nathalie Goemans¹¹, Janbernd Kirschner¹², Anna Kostera-Pruszczyk¹³, Jessica Braid¹⁴, Gergely Papp¹⁵, Ksenija Gorni¹⁶, Carmen Martin¹⁴, Renata Scalco¹⁷, Wai Yin Yeung¹⁴, Eugenio Mercuri⁵
¹IMotion Institut de Myologie AP-HP, Hôpital Armand Trousseau, Paris, France; MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, UK; Division of Child Neurology, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège & University of Liège, Liège, Belgium, ²Departments of Pediatrics and Neurology Neurosurgery, McGill University, Montreal, Canada, ³Department of Neurology, Stanford University, Palo Alto, CA, USA, ⁴Centre de Référence des Maladies Neuromusculaires, Children’s University Hospital, ULB, Brussels, Belgium; Neuromuscular Center, UZ Gent, Ghent, Belgium, ⁵Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy, ⁶Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER – ISC III, Barcelona, Spain, ⁷Medical Genetics Institute, Tokyo Women’s Medical University, Tokyo, Japan, ⁸Department of Pediatric Physical Medicine and Rehabilitation, Hôpital Mère Enfant, CHU-Lyon, Lyon, France; Neuromyogen Institute, CNRS UMR 5310 - INSERM U1217, Université de Lyon, Lyon, France, ⁹The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health University College London, & Great Ormond Street Hospital Trust, London, UK; Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, ¹⁰IMotion Institut de Myologie AP-HP, Hôpital Armand Trousseau, Paris, France; Université Paris Cité, UMR 1141, NeuroDiderot, Paris, France, ¹¹Neuromuscular Reference Centre, Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium, ¹²Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany, ¹³Department of Neurology, Medical University of Warsaw, Warsaw, Poland, ¹⁴Roche Products Ltd, Welwyn Garden City, UK, ¹⁵Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, ¹⁶PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland, ¹⁷Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland

Objective:

To determine the efficacy and safety of risdiplam (EVRYSDI®) in patients with Types 2 and 3 SMA after 48 months of treatment.

Background:

SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier that has been approved in over 90 countries worldwide.

Design/Methods:

SUNFISH (NCT02908685) is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2 and 3 SMA (inclusion criteria: aged 2–25 years at enrollment). Part 1 (N=51) assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2 and 3 SMA (ambulant and non-ambulant). Part 2 (N=180) assessed the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months; participants then received risdiplam in a blinded manner until Month 24. At Month 24, patients were offered the opportunity to enter the open-label extension phase.

Results:

The primary endpoint (Part 2) of change from baseline in the 32-item Motor Function Measure (MFM32) total score in risdiplam (n=120) versus placebo (n=60) was met at Month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment, as measured by changes in MFM32, Hammersmith Functional Motor Scale – Expanded, and Revised Upper Limb Module. At Month 36 (data-cut: 6 September 2021), there were no treatment-related safety findings leading to withdrawal from either SUNFISH Part 1 or 2. Here we present 48-month efficacy and safety data from SUNFISH.

Conclusions:

SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of children, teenagers and adults with SMA.