Neuropediatrics 2021; 52(S 01): S1-S53
DOI: 10.1055/s-0041-1739636
Abstract Salzburg

FIREFISH Part 2: 24-Month Efficacy and Safety of Risdiplam in Infants with Type 1 Spinal Muscular Atrophy (SMA)

B. T. Darras
1   Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
R. Masson
2   Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
,
M. Mazurkiewicz-Bełdzińska
3   Department of Developmental Neurology, Medical University of Gdańsk, Gdańsk, Poland
,
A. Klein
4   Neuropädiatrie, Inselspital Universitätsspital Bern, Universitätsklinik für Kinderheilkunde, Bern, Switzerland
5   University Children's Hospital Basel, Basel, Switzerland
,
K. Rose
6   Paediatric Gait Analysis Service of New South Wales, The Children's Hospital at Westmead, Sydney, Australia
,
H. Xiong
7   Department of Pediatrics, Peking University First Hospital, Beijing, China
,
E. Zanoteli
8   Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil
,
G. Baranello
2   Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
9   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
,
D. Vlodavets
10   Russian Children Neuromuscular Center, Veltischev Clinical Pediatric Research Institute, Pirogov Russian National Research Medical University, Moscow, Russia
,
A. Dodman
11   Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
M. El-Khairi
12   Roche Products Ltd, Welwyn Garden City, United Kingdom
,
M. Gerber
13   Pharma Development Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
K. Gorni
14   PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
H. Kletzl
15   Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland
,
R. S. Scalco
11   Pharma Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland
,
L. Servais
16   MDUK Oxford Neuromuscular Center, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
17   Division of Child Neurology, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Liège, Belgium
18   I-Motion - Hôpital Armand Trousseau, Paris, France
,
; on behalf of the FIREFISH Working Group › Author Affiliations
› Further Information
 
 

    Background/Purpose: Spinal muscular atrophy (SMA) is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (SMN) protein due to deletions/mutations of the SMN1 gene. A second SMN gene, SMN2, produces only low levels of functional SMN protein. Risdiplam is an oral SMN2 pre-mRNA splicing modifier that increases the 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 infants with Type 1 SMA after 24 months of treatment.

    Methods: FIREFISH (NCT02913482) is a multicenter, open-label, two-part study of risdiplam in infants with Type 1 SMA and two SMN2 gene copies (inclusion criteria 1–7 months at enrollment). Part 2 (N = 41) assesses efficacy/safety of the Part 1-selected dose of risdiplam.

    Results: The primary endpoint of Part 2 at 12 months was met (data-cut: 14th November 2019); 29% (p < 0.0001) of infants were able to sit without support for ≥5 seconds. This milestone was never achieved in natural history cohorts. After 12 months, risdiplam treatment also resulted in a significantly higher survival rate, due to improvements in motor function. No treatment-related safety findings leading to withdrawal were reported.

    We will present efficacy/safety data from infants who have received risdiplam for 24 months.

    Conclusion: The ongoing FIREFISH part 2 will provide important data on the long-term efficacy and safety of risdiplam in infants with Type 1 SMA.


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    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    28 October 2021

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