SUNFISH Parts 1 and 2: 4-year efficacy and safety data of risdiplam in Types 2 and 3 SMA

Topic:

Clinical Trials

Poster Number: 158

Author(s):

Maryam Oskoui, MD, MSc, FRCPC, FAAN, McGill University, John Day, MD, PhD, Stanford University, Nicolas Deconinck, MD, Universitair Ziekenhuis Gent, Elena Mazzone, DPT, MSc, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Rome, Italy, Andres Nascimento, MD, PhD, Hospital Sant Joan de Déu, Fundacion Sant Joan de Déu, CIBERER – ISC III, Kayoko Saito, MD, PhD, Institute of Medical Genetics, Tokyo Women’s Medical University, Carole Vuillerot, Department of Pediatric Physical Medicine and Rehabilitation, Hôpital Mère Enfant, CHU-Lyon, France, Giovanni Baranello, MD, Great Ormond Street Hospital for Children, Odile Boespflug-Tanguy, IMotion Institut de Myologie AP-HP, Hôpital Armand Trousseau, Paris, France, Nathalie Goemans, MD, PhD, University Hospitals Leuven, Janbernd Kirschner, PhD, University Medical Center Freiburg, Anna Kostera-Pruszczyk, MD, PhD, Department of Neurology, Medical University of Warsaw, Warsaw, Poland, Laurent Servais, MD, MDUK, Oxford, UK, Jessica Braid, Roche Products Ltd, Welwyn Garden City, UK, Marianne Gerber, MD, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Ksenija Gorni, MD PhD, Roche, 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, PhD, Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University

Background
Spinal muscular atrophy (SMA) 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 (SMN2) pre‑mRNA splicing modifier that has been approved in over 90 countries worldwide.

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.

Objectives
To determine the efficacy and safety of risdiplam in patients with Types 2 and 3 SMA after 4 years (48 months) 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. These increases in motor function were sustained in the second and third year after risdiplam treatment, as measured by changes in the 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 4-year 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.