[en] Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67-4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI - 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment.
Disciplines :
Pediatrics
Author, co-author :
Oskoui, Maryam ; Departments of Pediatrics and Neurology and Neurosurgery, McGill University, Montreal, Canada. maryam.oskoui@mcgill.ca
Day, John W ; Department of Neurology, Stanford University, Palo Alto, CA, USA
Deconinck, Nicolas ; Neuromuscular Reference Center, UZ Gent, Ghent, Belgium ; Centre de Référence des Maladies Neuromusculaires et Service de Neurologie Pédiatrique, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles, ULB, Brussels, Belgium
Mazzone, Elena S ; Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
Nascimento, Andres ; Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Fundacion Sant Joan de Deu, CIBERER-ISC III, Barcelona, Spain
Saito, Kayoko ; Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan
Vuillerot, Carole ; Department 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
Baranello, Giovanni ; The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London and Great Ormond Street Hospital Trust, London, UK ; Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Goemans, Nathalie ; Neuromuscular Reference Centre, Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium
Kirschner, Janbernd ; Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany
Kostera-Pruszczyk, Anna ; Department of Neurology, Medical University of Warsaw, Warsaw, Poland
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques ; I-Motion-Hôpital Armand Trousseau, Paris, France ; MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, UK
This study is sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Medical writing and editing support were funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ).The authors would like to thank all individuals enrolled in the risdiplam studies, their families, and the site staff involved. The authors would also like to thank the Spinal Muscular Atrophy Foundation and PTC Therapeutics for their collaboration in the SUNFISH study. Jen Ciarochi of Nucleus Global, wrote the first draft of the manuscript based on an outline agreed by all authors and provided medical writing assistance with subsequent drafts in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Medical editing support was provided by Megan Speakman of Nucleus Global.
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