Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies

BackgroundReducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models.ObjectiveExamine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD.MethodsTwo phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392.ResultsOverall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo.ConclusionsSKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms.

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Journal
Journal of Parkinson s Disease
Published
2024-12-27
DOI
https://doi.org/10.1177/1877718x241300295
Citations
7
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
2.58

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article

Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies

Caroline Moreau, Gilles Defer, David J. Burn, Ray Sheridan et al.
7 citations
Journal of Parkinson s Disease
Parkinson's Disease Mechanisms and Treatments
2.58
article

Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies

Caroline Moreau, Gilles Defer, David J. Burn, Ray Sheridan, Alfons Schnitzler, Nicola Pavese, Philippe Rémy, Christine Tranchant, Heidi Pape, Christian Gény, Fernando Tricta, Jason Raw, Noemi Toiber Temin, Camille Carroll, Téodor Danaila, Alexandra Foubert‐Samier, Olivier Rascol, David Devos, Philippe Couratier, Andrew Evans, Karla Eggert, Sophie Drapier, Oksana Suchowersky, Lorraine V. Kalia, David Maltête, Simon J.G. Lewis, Mathieu Anheim, Wassilios G. Meissner, Caroline Fradette, Jean-Christophe Corvol, Daniela Berg
article en
7 citations

Abstract

BackgroundReducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models.ObjectiveExamine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD.MethodsTwo phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392.ResultsOverall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo.ConclusionsSKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms.

Journal of Parkinson s DiseaseVol. 15(1)
Pennine Acute Hospitals NHS Trust (GB), Centre National de la Recherche Scientifique (FR), The University of Sydney (AU), The Royal Melbourne Hospital (AU), University Health Network (CA), Université de Bordeaux (FR), University of Alberta (CA), Inserm (FR), Philipps University of Marburg (DE), Université Paris-Est Créteil (FR), Université de Montpellier (FR), Université de Lille (FR), Toronto Western Hospital (CA), Royal Devon and Exeter Hospital (GB), Christian-Albrechts-Universität zu Kiel (DE), Sorbonne Université (FR), Institut de génétique et de biologie moléculaire et cellulaire (FR), Institut des Maladies Neurodégénératives (FR), Différenciation et Communication Neuronale et Neuroendocrine (FR), Centre Hospitalier Universitaire de Montpellier (FR), Assistance Publique – Hôpitaux de Paris (FR), Hospices Civils de Lyon (FR), University Hospital Schleswig-Holstein (DE), CIC Rennes (FR), Centre Hospitalier Universitaire de Limoges (FR), Hôpitaux Universitaires de Strasbourg (FR), Institut du Cerveau (FR), Centre Hospitalier Universitaire de Rennes (FR), Institut Mondor de Recherche Biomédicale (FR), French Clinical Research Infrastructure Network (FR), Heinrich Heine University Düsseldorf (DE), Université de Rouen Normandie (FR), Université de Strasbourg (FR), Newcastle University (GB), University of Plymouth (GB), University of Lübeck (DE), Université de Caen Normandie (FR)
Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Medtronic, Biogen, Teva Pharmaceutical Industries, Alexion Pharmaceuticals, Boston Scientific Corporation, Sunovion, Acorda Therapeutics, Chiesi USA, Parkinson's UK, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire de Toulouse, Association France Parkinson, EVER Neuro Pharma, Servier, H. Lundbeck A/S, Sun Pharma, Ipsen, Allergan, Horizon 2020 Framework Programme, Sanofi Genzyme, Direction de l’hospitalisation et de l’offre de Soins
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Openalex Percentile: Top 9%
Parkinson's Disease Mechanisms and Treatments
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