Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration

• Type of Material: Article
• Authors: Thomas Klopstock, University Hospital, Ludwig Maximilians University Munchen; Aleksander Videnovic, Harvard Medical School; Almut T Bischoff, University Hospital, Ludwig Maximilians University Munchen; Cecilia Bonnet, Sorbonne Universite; Laura Cif, CHRU de Montpellier, Gui de Chauliac Hospital; Cynthia Comella, Rush University; Marta Correa-Vela, Hospital Universitari Vall d'Hebron; Maria L Escolar, University of Pittsburgh; Jamie L Fraser, Children's National Medical Center; Victoria Gonzalez, University Hospital of Montpellier; Neal Hermanowicz, University of California Irvine; Robert Jech, Charles University Prague; Hyder Jinnah, Emory University; Tomasz Kmiec, Children's Memorial Health Institute, Poland; Anthony Lang, Toronto Western Hospital; Maria J Martí, Hospital Clinic of Barcelona; Saadet Mercimek-Andrews, University of Toronto; Migvis Monduy, Nicklaus Children's Hospital; Graeme AM Nimmo, University of Toronto; Belen Perez‐Dueñas, Hospital Universitari Vall d'Hebron; Helle Cecilie Viekilde Pfeiffer, Oslo University Hospital; Lluis Planellas, Hospital Clinic of Barcelona; Emmanuel Roze, Sorbonne Universite; Nivedita Thakur, University of Texas at Houston Medical School; Laura Tochen, Children's National Medical Center; Nora Vanegas-Arroyave, Columbia University College of Physicians and Surgeons; Giovanna Zorzi, Fondazione IRCCS Istituto Neurologico Carlo Besta; Colleen Burns, Retrophin Inc; Feriandas Greblikas, Retrophin Inc
• Language: English
• Date: 2020-11-16
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/mds.28392
• Title of Journal or Parent Work: MOVEMENT DISORDERS
• Volume: 36
• Issue: 6
• Start Page: 1342
• End Page: 1352
• Grant/Funding Information: The FORT trial was supported by Retrophin, Inc.
• Keywords: RELIABILITY; SCALE; METABOLISM; Life Sciences & Biomedicine; fosmetpantotenate; pantothenate kinase– randomized controlled trial; Neurosciences & Neurology; PANK2; associated neurodegeneration; Science & Technology; treatment; DYSTONIA; Clinical Neurology
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

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. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.