SUNFISH Parts 1 and 2: 5-year efficacy and safety data of risdiplam in Types 2 and 3 spinal muscular atrophy

Topic:

Clinical Trials

Poster Number: P94

Author(s):

Laurent Servais, MD, PhD, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, Oxford, UK, John Day, MD, PhD, Stanford School of Medicine, Nicolas Deconinck, MD, Neuromuscular Reference Center, UZ Gent, Ghent, Belgium, Elena S Mazzone, PT, PhD, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy, Andres Nascimento, MD, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER – ISC III, Barcelona, Spain, Maryam Oskoui, MD, Department of Pediatrics and Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada, Kayoko Saito, MD, Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan, Carole Vuillerot, MD, Hôpital Mère Enfant, CHU-Lyon, Bron, France, Giovanni Baranello, MD, Great Ormond Street Institute of Child Health University College London, London, UK, Odile Boespflug-Tanguy, MD, I-Motion, Institut de Myologie AP-HP, Hôpital Armand Trousseau, Paris, France, Nathalie Goemans, MD, Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium, Janbernd Kirschner, MD, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw & ERN EURO-NMD, Warsaw, Poland, Kate Sully, PhD, Roche Products Ltd, Welwyn Garden City, UK, Manni Kuthiala, MSc, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Ksenija Gorni, MD, PhD, PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Carmen Martin, PhD, Roche Products Ltd, Welwyn Garden City, UK, Wai Yin Yeung, PhD, Roche Products Ltd, Welwyn Garden City, UK, Renata S Scalco, MD, PhD, Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Eugenio Mercuri, MD, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy

Background
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier, approved in more than 100 countries worldwide.

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

Objectives
This analysis assesses the efficacy and safety of risdiplam in patients with Types 2/3 SMA after 5 years of treatment.

Results
The primary endpoint (Part 2) of change from baseline in the 32-item Motor Function Measure (MFM32) total score in patients treated with risdiplam (n=120) versus placebo (n=60) was met at Month 12. Previously reported results showed that increases in motor function were sustained over 4 years of risdiplam treatment, as measured by MFM32, Hammersmith Functional Motor Scale – Expanded, and Revised Upper Limb Module. After 4 years of risdiplam treatment, there were no treatment-related safety findings leading to withdrawal from SUNFISH Part 1 or 2.

Here we present for the first time, the final efficacy and safety results from the SUNFISH study after 5 years of risdiplam treatment (data cutoff: October 2, 2023).

Conclusion
SUNFISH provides long-term efficacy and safety data of risdiplam in a broad population of children, teenagers and adults with Types 2/3 SMA.