PDF icon Download PDF
Open Access
CC BY 4.0 · Arq Neuropsiquiatr 2024; 82(S 02): S53-S176
DOI: 10.1055/s-0045-1807151
ID: 783
Area: Neuromuscular diseases
Presentation method: Presentation Poster

FIREFISH parts 1 and 2: 4-year efficacy and safety of risdiplam in type 1 spinal muscular atrophy

Edmar Zanoteli
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
,
Giovanni Baranello
2   The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health University College London, Great Ormond Street Hospital Trust, London, United Kingdom.
3   Fondazione IRCCS Istituto Neurologico Carlo Besta, Developmental Neurology Unit, Milan, Italy.
,
Odile Boespflug-Tanguy
4   Hôpital Armand Trousseau, I-Motion Institut de Myologie AP-HP, Paris, France.
5   Université de Paris, UMR 1141, NeuroDiderot, Paris, France.
,
John W. Day
6   Stanford University, Department of Neurology, Palo Alto, California, United States.
,
Nicolas Deconinck
7   Neuromuscular Reference Center, UZ Gent, Ghent, Belgium,
8   Université Libre de Bruxelles, Queen Fabiola Children’s University Hospital, Centre de Référence des Maladies Neuromusculaires, Brussels, Belgium.
,
Andrea Klein
9   University Children’s Hospital Basel, Paediatric Neurology, Basel, Switzerland.
10   University of Bern, Bern University Hospital, Inselspital, Department of Paediatrics, Division of Neuropaediatrics, Bern, Switzerland.
,
Riccardo Masson
3   Fondazione IRCCS Istituto Neurologico Carlo Besta, Developmental Neurology Unit, Milan, Italy.
,
Maria Mazurkiewicz-Bełdzińska
11   Medical University of Gdańsk, Department of Developmental Neurology, Gdańsk, Poland.
,
Eugenio Mercuri
12   Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, Pediatric Neurology Institute, Rome, Italy.
,
Kristy Rose
13   University of Sydney and Sydney Children’s Hospital Network, Faculty of Medicine and Health, Discipline of Physiotherapy, Sydney, Australia.
,
Laurent Servais
4   Hôpital Armand Trousseau, I-Motion Institut de Myologie AP-HP, Paris, France.
14   University of Oxford, Oxford, MDUK Oxford Neuromuscular Centre, Department of Paediatrics, United Kingdom.
15   University of Liège, Centre de Références des Maladies Neuromusculaires, Department of Pediatrics, Division of Child Neurology, Liège, Belgium.
,
Dmitry Vlodavets
1   Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
,
COMP Last name
17   Peking University First Hospital, Department of Pediatrics, Beijing, China.
,
Hui Xiong
6   Stanford University, Department of Neurology, Palo Alto, California, United States.
,
Muna El-Khairi
18   Roche Products Ltd, Welwyn Garden City, United Kingdom.
,
Marianne Gerber
19   F. Hoffmann-La Roche Ltd, Pharma Development, Safety, Basel, Switzerland.
,
Ksenija Gorni
20   F. Hoffmann-La Roche Ltd, PDMA Neuroscience and Rare Disease, Basel, Switzerland.
,
Heidemarie Kletzl
21   Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, Basel, Switzerland.
,
Laura Palfreeman
18   Roche Products Ltd, Welwyn Garden City, United Kingdom.
,
Angela Dodman
22   F. Hoffmann-La Roche Ltd, Pharma Development Neurology, Basel, Switzerland.
,
Basil T. Darras
23   Harvard Medical School, Boston Children’s Hospital, Department of Neurology, Boston, Massachusetts, United States.
,
on behalf of the FIREFISH Study Group
› Author Affiliations
› Further Information
Also available ateRef
 
 PDF Download Permissions and Reprints

    *Correspondence: edmar.zanoteli@usp.br.

    Abstract

    Background: Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier, approved in more than 90 countries worldwide.

    Objective: To assess the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam doses.

    Methods: FIREFISH (NCT02913482) is a multicenter, open-label, two-part study of risdiplam in children with Type 1 spinal muscular atrophy (SMA) and two SMN2 gene copies (inclusion criteria: 1–7 months old at enrollment). FIREFISH Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam doses. Pivotal Part 2 assessed the safety and efficacy of risdiplam over 24 months at the dose selected from Part 1. Thereafter, children entered a 3-year open-label extension phase and continue to receive risdiplam at the pivotal dose.

    Results: Pooled safety and efficacy data were available from 58 enrolled infants who received risdiplam treatment (Part 1 high-dose cohort, n=17, and Part 2, N=41). As of the cut-off date (23 November, 2021), there were no treatment-related adverse events leading to withdrawal, no additional deaths and no additional children meeting the definition of permanent ventilation since Month 24. At Month 36, 84% of children were alive and did not require permanent ventilation. Children either maintained or improved their motor skills in terms of developmental milestones and motor function between Months 24 and 36, which is not observed in natural history.

    Conclusion: Here we present longer-term pooled safety and efficacy data from children who have received risdiplam at the pivotal dose for at least 48 months. FIREFISH Parts 1 and 2 are ongoing globally and will provide further safety and efficacy data of risdiplam in the treatment of Type 1 SMA.


     

    Publication History

    Article published online:
    12 May 2025

    © 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

    Thieme Revinter Publicações Ltda.
    Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

      Permissions and Reprints