Maria L. Escolar, Neal Hermanowicz, María José Martí, Giovanna Zorzi, Graeme A. M. Nimmo, Laura Tochen, Saadet Mercimek-Andrews, Almut Turid Bischoff, Jamie L. Fraser, Hyder A. Jinnah, Tomasz Kmieć, Laura Cif, Victoria Gonzalez, Robert Jech, Aleksandar Videnovic, Marta Correa-Vela, Cecilia Bonnet, Feriandas Greblikas, Thomas Klopstock, Belén Pérez-Dueñas, Migvis Monduy, Nora Vanegas-Arroyave, Helle Cecilie Viekilde Pfeiffer, Colleen Burns, Cynthia L. Comella, Emmanuel Roze, Lluís Planellas, Anthony E. Lang, Nivedita Thakur, Institut Català de la Salut, [Klopstock T] Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany. German Center for Neurodegenerative Diseases (DZNE), Munich, Munich, Germany. Munich Cluster for Systems Neurology (SyNergy), Munich, Munich, Germany. [Videnovic A] Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. [Bischoff AT] Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany. [Bonnet C] Department of Neurology, Sorbonne University, AP-HP Salpêtrière Hospital, Paris, France. [Cif L] Department of Neurosurgery, CHRU de Montpellier, Gui de Chauliac Hospital, Montpellier, France. [Comella C] Department of Neurosurgery and Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. [Correa-Vela M, Perez-Dueñas B] Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Fosmetpantotenate; Randomized controlled trial Fosmetpantotenato; Ensayo controlado aleatorizado Fosmetpantotenat; Assaig controlat aleatoritzat 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. The FORT trial was supported by Retrophin, Inc.