TY - JOUR
T1 - Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration
AU - Klopstock, Thomas
AU - Videnovic, Aleksandar
AU - Bischoff, Almut Turid
AU - Bonnet, Cecilia
AU - Cif, Laura
AU - Comella, Cynthia
AU - Correa-Vela, Marta
AU - Escolar, Maria L.
AU - Fraser, Jamie L.
AU - Gonzalez, Victoria
AU - Hermanowicz, Neal
AU - Jech, Robert
AU - Jinnah, Hyder A.
AU - Kmiec, Tomasz
AU - Lang, Anthony
AU - Martí, Maria J.
AU - Mercimek-Andrews, Saadet
AU - Monduy, Migvis
AU - Nimmo, Graeme A.M.
AU - Perez-Dueñas, Belen
AU - Pfeiffer, Helle Cecilie Viekilde
AU - Planellas, Lluis
AU - Roze, Emmanuel
AU - Thakur, Nivedita
AU - Tochen, Laura
AU - Vanegas-Arroyave, Nora
AU - Zorzi, Giovanna
AU - Burns, Colleen
AU - Greblikas, Feriandas
N1 - Funding Information:
Aleksandar Videnovic provides consulting services to Retrophin, Inc., and receives active grant support from the National Institutes of Health (NIH); provides consulting services to Acadia, Jazz, and Roche; and has served on DSMB for Wilson Therapeutics and Acorda.
Funding Information:
HyderA. Jinnah provides consulting services to Retrophin, Inc.; has received active or recent grant support from the US government (NIH), academically oriented institutions (the Dystonia Study Group), and industry (Cavion Therapeutics, Ipsen Pharmaceuticals, Retrophin, Inc.); serves on advisory boards or as a consultant for Allergan Inc., CoA Therapeutics, Psyadon Pharmaceuticals, and Medtronic, Inc.; has received honoraria or stipends for lectures or administrative work from the American Academy of Neurology, Dystonia Medical Research Foundation, International Neurotoxin Society, International Parkinson's Disease and Movement Disorders Society, Parkinson's Disease Foundation; serves on scientific advisory boards for Cure Dystonia Now, Dystonia Medical Research Foundation, Tourette Association of America, and Tyler's Hope for a Cure; and serves as principal investigator for the Dystonia Coalition, which receives the majority of its support through NIH grants from the NINDS and the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences. The Dystonia Coalition has received additional material or administrative support from industry sponsors (Allergan, Inc. and Merz Pharmaceuticals) and from private foundations (American Dystonia Society, Beat Dystonia, Benign Essential Blepharospasm Foundation, Cure Dystonia Now, Dystonia Inc., Dystonia Ireland, Dystonia Medical Research Foundation, European Dystonia Federation, Foundation for Dystonia Research, National Spasmodic Dysphonia Association, and National Spasmodic Torticollis Association).
Funding Information:
Anthony Lang reports consultancy support from Abbvie, AFFiRis, Biogen, Janssen, Lilly, Lundbeck, Merck, Paladin, Roche, Sun Pharma, Theravance, and Corticobasal Degeneration Solutions; advisory board support form Jazz Pharma, PhotoPharmics, Sunovion; other honoraria from Sun Pharma, AbbVie, Sunovion, American Academy of Neurology, and the International Parkinson and Movement Disorder Society; grants from Brain Canada, Canadian Institutes of Health Research, Corticobasal Degeneration Solutions, Edmond J Safra Philanthropic Foundation, Michael J. Fox Foundation, the Ontario Brain Institute, Parkinson Foundation, Parkinson Canada, and W. Garfield Weston Foundation, and royalties from Elsevier, Saunders, Wiley‐Blackwell, Johns Hopkins Press, and Cambridge University Press.
Funding Information:
Maria J. Martí has received honoraria for lectures from Allergan Inc. and Merz Pharmaceutical, and grants from Fundacio la Marato TV3, Fondo de Investigación Sanitaria‐ISCIII, and Michael J. Fox Foundation.
Funding Information:
Saadet Mercimek‐Andrews received research support for the study site supervision and administration of the FORT trial from Retrophin, Inc.; received honoraria for lectures and advisory board for epilepsy genetics from Biomarin Pharmaceutical; received investigator‐initiated funding from Genzyme; and received honoraria from Recordati Rare Diseases for organizing a workshop and being an advisory board member.
Funding Information:
Belen Perez‐Dueñas receives research grant support from Retrophin, Inc., to Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Funding Information:
Helle Cecilie Viekilde Pfeiffer reports advisory board support from Octapharma AG and has received grants from the Danish Parkinson's Disease Association and the Norwegian Research Council, as well as the South‐Eastern Norway Regional Health Authority Research Trust.
Funding Information:
Emmanuel Roze served on scientific advisory boards for Orkyn, Aguettant, and Merz‐Pharma; received honoraria for speeches from Orkyn, Aguettant, Merz‐Pharma, Everpharma, International Parkinson and Movement Disorder Society; received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Everpharma, Fondation Desmarest, AMADYS, Fonds de Dotation Brou de Laurière, and Agence Nationale de la Recherche; and received travel grants from Vitalair, PEPS development, Aguettant, Merz‐Pharma, Ipsen, Merck, Orkyn, Elivie, Adelia Medical, Dystonia Medical Research Foundation, International Parkinson and Movement Disorder Society, European Academy of Neurology, and International Association of Parkinsonism and Related Disorders.
Funding Information:
Nivedita Thakur provides consulting services to Retrophin, Inc. and receives grant support from Retrophin, Inc.
Funding Information:
Nora Vanegas‐Arroyave received consulting honoraria from Neurocrine and research support from the NIH and the Parkinson's Disease Foundation.
Funding Information:
Giovanna Zorzi receives grant support from Retrophin, Inc., and provides consulting services to Medtronic, Inc.
Funding Information:
Thomas Klopstock serves as coordinating investigator of the FORT trial and receives research funding from Retrophin, Inc.
Funding Information:
Belen Perez‐Dueñas receives research grant support from Retrophin, Inc.
Funding Information:
Nivedita Thakur provides consulting services to Retrophin, Inc., and receives grant support from Retrophin, Inc.
Funding Information:
Giovanna Zorzi receives grant support from Retrophin, Inc.
Publisher Copyright:
© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. Results: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN.
AB - Background: Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. Results: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN.
KW - fosmetpantotenate
KW - pantothenate kinase–associated neurodegeneration
KW - randomized controlled trial
KW - treatment
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U2 - 10.1002/mds.28392
DO - 10.1002/mds.28392
M3 - Article
C2 - 33200489
AN - SCOPUS:85096723730
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
ER -