Neuropediatrics 2023; 54(S 01): S1-S32
DOI: 10.1055/s-0043-1777160
Neuromuskuläre Erkrankungen

Givinostat in Duchenne Muscular Dystrophy: Effect on Disease Milestones

Authors

  • C. McDonald

    1   University of California Davis Health, Sacramento, Vereinigte Staaten von Amerika

  • L. Servais

    2   Division of Child Neurology, Centre de Reference des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liege and University of Liege, Liege, Belgien

  • F. Munell

    3   Servicio de Neurología Pediátrica, Hospital Universitari Vall d'Hebron, Barcelona, Spanien

  • U. Schara Schmidt

    4   Department of Paediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Clinic Essen, Essen, Deutschland

  • E. Bettini

    5   Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambin Gesù Children's Hospital, Rom, Italien

  • G. Comi

    6   Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italien

  • A. Blaschek

    7   LMU Munich, Dr. v. Haunerschen Kinderspital, München, Deutschland

  • J. Johannsen

    8   Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Deutschland

  • S. Cazzaniga

    9   Italfarmaco Spa, Milano, Italien

  • P. Bettica

    9   Italfarmaco Spa, Milano, Italien

  • K. Vandenborne

    10   Pediatric Neurology, Department of Woman and Child Health and Public Health, Child Health Area, Catholic University, Rom, Italien

  • E. Mercuri

    11   Paediatric Neurology and Centro Clinico Nemo, Catholic University, Rome, Italien
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Background: Givinostat is a novel orally active histone deacetylase inhibitor being developed for the treatment of Duchenne muscular dystrophy (DMD).

Methods: Givinostat efficacy and safety were assessed in the EPIDYS study, a randomized, double blind, placebo controlled, multicenter Phase 3 study in ambulant DMD patients (NCT02851797). Study DSC/14/2357/51 (NCT03373968) is an ongoing open label, long-term study of Givinostat. Long-term efficacy was evaluated by comparing patients enrolled in EPIDYS study and study DSC/14/2357/51 to matched patients from imaging DMD (NCT01484678) and the CINRG (NCT00468832) natural history studies.

Results: A total of 148 boys treated with Givinostat were compared with 197 boys enrolled in the natural history studies treated with steroids. Transition beyond all specific disease progression milestones was significantly delayed by Givinostat treatment (on top of steroid treatment). In particular, median age at first rise from floor > 10 seconds was delayed by 1.7 years (HR, mean [95% CI] = 0.62 [0.45,0.84]; p = 0.003). Median age at first 10-m walk/run > 10 seconds was delayed by 3.5 years (HR, mean [95% CI] = 0.43 [0.29, 0.64]; p < 0.0001). Median age at loss of rise from floor was delayed by 2.2 years (HR, mean [95% CI] = 0.68 [0.47, 0.97]; p = 0.034). Median age at loss of 4 standard stairs climb (4SC) was delayed by 3.3 years (HR, mean [95% CI] = 0.42 [0.26, 0.67]; p < 0.0001). Median age at loss of ambulation was delayed by 2,7 years (HR, mean [95% CI] = 0.48 [0.27, 0.86]; p = 0.012).

Conclusion: Results show that Givinostat can delay clinically meaningful DMD disease milestones beyond the expected delays observed with standard of care steroids. These results confirm Givinostat efficacy demonstrated in the EPIDYS study with longer-term treatment.


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

Publication History

Article published online:
13 November 2023

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