SUNFISH Part 2: 24-month efficacy of risdiplam compared with external control comparators


Clinical Trials

Poster Number: Virtual


Laurent Servais, I-Motion Institute, Hôpital Armand Trousseau, John Day, MD, PhD, Stanford University, Nicolas Deconinck, MD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des E, Elena S Mazzone, DPT, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Andres Nascimento, MD, PhD, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER – ISC III, Maryam Oskoui, MD, MSc, FRCPC, FAAN, Departments of Pediatrics and Neurology Neurosurgery, McGill University, Kayoko Saito, MD, PhD, Institute of Medical Genetics, Tokyo Women’s Medical University, Carole Vuillerot, Hôpital Mère Enfant, CHU-Lyon; Université de Lyon, Giovanniu Baranello, MD, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK., Odile Boespflug-Tanguy, Hôpital Armand Trousseau; Université de Paris, UMR 1141, NeuroDiderot, Nathalie Goemans, MD, PhD, University Hospitals Leuven, Leuven, Belgium, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Marianne Gerber, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Ksenija Gorni, MD, PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Carmen Martin, Roche Products Ltd, Tammy McIver, Roche Products Ltd, Renata S Scalco, Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Wai Yin Yeung, Roche Products Ltd, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion

Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second gene, SMN2, produces only low levels of functional SMN protein. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre?mRNA splicing modifier that has been approved by the FDA for the treatment of patients with SMA aged 2 months and older.

SUNFISH (NCT02908685) is a multicenter, two-part, randomized, placebo-controlled, double-blind study in a broad population of patients with Type 2/3 SMA aged 2–25 years at enrollment. Part 1 (N=51) assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in Type 2/3 SMA (ambulant and non-ambulant). Part 2 (N=180) assesses 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; all participants then received risdiplam until Month 24, when patients were offered the opportunity to enter the open-label extension phase.

To compare 24-month efficacy results from SUNFISH Part 2 with data from an external control.

The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Here, we report the results of an analysis that compares data from patients in SUNFISH Part 2 who have been treated with risdiplam for 24 months with an external comparator dataset. The external comparator comprises data from the NatHis-SMA study (NCT02391831), a prospective, longitudinal natural history study of patients with Type 2/3 SMA, and from participants in the placebo arm of a Phase 2 study of olesoxime in patients with SMA (NCT01302600).

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.