SUNFISH Parts 1 and 2: 3-year efficacy and safety of risdiplam in Types 2 and 3 SMA

Topic:

Clinical Trials

Poster Number: 73

Author(s):

John Day, MD, PhD, Stanford University, Nicolas Deconinck, MD, Centre de Référence Neuromusculaire and Paediatric Neurology Department, Hôpital Universitaire des E, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, 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, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Laurent Servais, I-Motion Institute, Hôpital Armand Trousseau, Jessica Braid, Roche Products Ltd, 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, 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

Background
Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease that affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 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 (2:1, risdiplam: placebo), placebo-controlled, double-blind study in a broad population of patients with Types 2 and 3 SMA (inclusion criteria 2–25 years at enrollment). Part 1 (N=51) assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in Types 2 and 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. At Month 24, patients were offered the opportunity to enter the open-label extension phase.

Objective
SUNFISH aims to determine the efficacy and safety of risdiplam in patients with Types 2 and 3 SMA who have received this treatment for 3 years (36 months).

Results
The primary outcome of Part 2 was met, showing a statistically significant difference in the change from baseline in 32-item Motor Function Measure total score at Month 12 in patients treated with risdiplam (n=120) versus placebo (n=60). The gains observed with risdiplam treatment at Month 12 were maintained or improved upon at Month 24. At Month 24, there were no treatment-related safety findings leading to withdrawal. We will present SUNFISH efficacy and safety data after 3 years of risdiplam treatment.

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.