Neuropediatrics 2021; 52(S 01): S1-S53
DOI: 10.1055/s-0041-1739637
Abstract Salzburg

SUNFISH Part 2: 24-Month Efficacy and Safety of Risdiplam in Patients with Type 2 or Non-Ambulant Type 3 Spinal Muscular Atrophy

M. Oskoui
1   Departments of Pediatrics and Neurology and Neurosurgery, McGill University, Montreal, Canada
,
J. W. Day
2   Department of Neurology, Stanford University, Palo Alto, California, United States
,
N. Deconinck
3   Neuromuscular Reference Center, UZ Gent, Ghent, Belgium
4   Queen Fabiola Children's University Hospital, ULB, Brussels, Belgium
,
J. Kirschner
5   Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Freiburg, Germany
6   Division of Neuropediatrics, Faculty of Medicine, University Hospital Bonn, Bonn, Germany
,
E. Mazzone
7   Paediatric Neurology and Nemo Center, Catholic University and Policlinico Gemelli, Rome, Italy
,
A. Nascimento
8   Neuromuscular Unit, Neuropaediatrics Department, Hospital Sant Joan de Déu, Fundacion Sant Joan de Deu, CIBERER – ISC III, Barcelona, Spain
,
K. Saito
9   Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan
,
C. Vuillerot
10   Service de Rééducation Pédiatrique Infantile “L’Escale,” Hôpital Femme Mère Enfant, CHU-Lyon, Université de Lyon, France
,
G. Baranello
11   The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health University College London, and Great Ormond Street Hospital Trust, London, United Kingdom
12   Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
,
O. Boespflug-Tanguy
13   I-Motion - Hôpital Armand Trousseau, Paris, France
,
N. Goemans
14   Neuromuscular Reference Centre, Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium
,
A. Kostera-Pruszczyk
15   Katedra I Klinika Neurologii Warszawskiego Uniwersytetu, Warsaw, Poland
,
L. Servais
13   I-Motion - Hôpital Armand Trousseau, Paris, France
16   MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
17   Reference Center for Neuromuscular Disease, Centre Hospitalier Régional de La Citadelle, Liège, Belgium
,
M. Gerber
18   Pharma Development Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
K. Gorni
19   PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
H. Kletzl
20   Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland
,
C. Martin
19   PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
R. S. Scalco
21   Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
H. Staunton
22   Roche Products Ltd, Welwyn Garden City, United Kingdom
,
W. Y. Yeung
22   Roche Products Ltd, Welwyn Garden City, United Kingdom
,
E. Mercuri
7   Paediatric Neurology and Nemo Center, Catholic University and Policlinico Gemelli, Rome, Italy
,
; on behalf of the SUNFISH Working Group › Author Affiliations
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Background/Purpose: 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/mutations of the SMN1 gene. Another gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is an oral SMN2 pre-mRNA splicing modifier that increases levels of functional SMN protein and has been approved by the FDA for the treatment of patients with SMA, aged ≥2 months. This study's purpose is to determine the efficacy and safety of risdiplam in patients with Type 2 and non-ambulant Type 3 SMA after 24 months of treatment.

Methods: 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 2/3 SMA (inclusion criteria 2–25 years at enrollment). Part 2 assessed efficacy/safety of the Part 1-selected dose of risdiplam. Individuals were treated with risdiplam or placebo for 12 months, and then all received risdiplam until month 24. Afterward, patients had the opportunity to enter the open-label extension phase.

Results: The primary outcome of the study was met, showing a statistically significant difference in the change from baseline in MFM32 total score at month 12 between risdiplam (N = 120) and placebo (N = 60). No treatment-related safety findings leading to withdrawal were reported.

We will present efficacy/safety data after 24 months of treatment.

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



Publication History

Article published online:
28 October 2021

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