SUNFISH Part 2: 24-month efficacy and safety of risdiplam in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA)

Clinical Trials
80
Maryam Oskoui MD, MSc, FRCPC, FAAN, John W Day , Nicolas Deconinck , Elena Mazzone DPT, Andres Nascimento MD, PhD, Kayoko Saito , Carole Vuillerot , Giovanni Baranello , Odile Boespflug-Tanguy , Nathalie Goemans MD, PhD, Janbernd Kirschner , Anna Kostera-Pruszczyk , Laurent Servais MD, PhD, Marianne Gerber MD, Ksenija Gorni MD, PhD, Heidemarie Kletzl , Carmen Martin , Renata S Scalco , Hannah Staunton , Wai Yin Yeung , Eugenio Mercuri MD, PhD
1. Departments of Pediatrics and Neurology Neurosurgery, McGill University, 2. Department of Neurology, Stanford University, 3. Neuromuscular Reference Center, UZ Gent, 4. Paediatric Neurology and Nemo Center, Catholic University and Policlinico Gemelli, 5. Neuromuscular Unit, Hospital Sant Joan de Déu, Fundacion Sant Joan de Deu, 6. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan, 7. Service de Rééducation Pédiatrique Infantile “L’Escale”, Hôpital Femme Mère Enfant, CHU-Lyon, 8. The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, 9. I-Motion - Hôpital Armand Trousseau, 10. Neuromuscular Reference Center for Children, University Hospitals Leuven, 11. Clinic for Neuropediatrics and Muscle Disease, University Medical Center Freiburg, Freiburg, Germany, 12. Katedra I Klinika Neurologii Warszawskiego Uniwersytetu, 13. MDUK Oxford Neuromuscular Centre, 14. Pharma Development, Safety, F. Hoffmann-La Roche Ltd, 15. PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, 16. Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, 17. PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, 18. Pharma Development Neurology, F. Hoffmann-La Roche Ltd, 19. Roche Products Ltd, 20. Roche Products Ltd, 21. Universita Cattolica del Sacro Cuore

Background:
Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of the survival of motor neuron (SMN) protein due to deletions and/or mutations of the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases levels of functional SMN protein. Risdiplam (EVRYSDI™) 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 Type 2/3 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 2/3 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. Individuals were treated with risdiplam or placebo for 12 months; all individuals then received risdiplam until Month 24. At Month 24, patients were offered the opportunity to enter the open-label extension phase.

Objective:
To determine the efficacy and safety of risdiplam in patients with Type 2 and non-ambulant Type 3 SMA after 24 months of treatment.

Results:
In Part 2, the primary outcome of the study was met, showing a statistically significant difference in the change from baseline in 32-item Motor Function Measure total score at Month 12 between patients treated with risdiplam (N=120) and placebo (N=60). No treatment-related safety findings leading to withdrawal were reported. For the first time, we will present SUNFISH Part 2 efficacy and safety data after 24 months of treatment.

Conclusion:
SUNFISH Part 2 is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of children, teenagers and adults.