Fosmetpantotenate(Fosmetpantotenate) - 在研适应症：泛酸激酶相关神经变性_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Fosmetpantotenate (USAN)

靶点-

作用机制-

治疗领域

神经系统疾病遗传病与畸形其他疾病

在研适应症

泛酸激酶相关神经变性

非在研适应症-

原研机构

Travere Therapeutics, Inc.

在研机构-

非在研机构

Travere Therapeutics, Inc.

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C20H31N2O9P

InChIKeyHUWUHKIPYXWUPN-YVRVQSMLSA-N

CAS号1858268-66-2

关联

2

项与 Fosmetpantotenate 相关的临床试验

EUCTR2016-001955-29-CZ

/ Not yet recruiting临床3期

Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate replacement therapy, in patients with Pantothenate Kinase-associated Neurodegeneration (PKAN): A Randomized, Double-blind, Placebo-Controlled Study with an Open-Label Extension

开始日期2017-10-06

申办/合作机构-

NCT03041116

/ Terminated临床3期

Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate Replacement Therapy, in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Patients: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension

This study investigated whether fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy, was safe and effective in treating participants with PKAN.

开始日期2017-07-17

申办/合作机构

Travere Therapeutics, Inc.

100 项与 Fosmetpantotenate 相关的临床结果

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100 项与 Fosmetpantotenate 相关的转化医学

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100 项与 Fosmetpantotenate 相关的专利（医药）

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8

项与 Fosmetpantotenate 相关的文献（医药）

2021-09-01·Movement Disorders1区 · 医学

Rational Design of Novel Therapies for Pantothenate Kinase–Associated Neurodegeneration

1区 · 医学

Review

作者: Videnovic, Aleksandar ; Jinnah, Hyder A. ; Klopstock, Thomas ; Jackowski, Suzanne ; Kuscer, Enej ; Tricta, Fernando ; Thakur, Nivedita

ABSTRACTBackgroundThis review highlights the recent scientific advances that have enabled rational design of novel clinical trials for pantothenate kinase‐associated neurodegeneration (PKAN), a rare autosomal recessive neurogenetic disorder associated with progressive neurodegenerative changes and functional impairment. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in pantothenate kinase 2 (PANK2) enzyme activity, with consequent disruption of coenzyme A (CoA) synthesis, and subsequent accumulation of brain iron. The clinical phenotype is varied and may include dystonia, rigidity, bradykinesia, postural instability, spasticity, loss of ambulation and ability to communicate, feeding difficulties, psychiatric issues, and cognitive and visual impairment. There are several symptom‐targeted treatments, but these do not provide sustained benefit as the disorder progresses.ObjectivesA detailed understanding of the molecular and biochemical pathogenesis of PKAN has opened the door for the design of novel rationally designed therapeutics that target the underlying mechanisms.MethodsTwo large double‐blind phase 3 clinical trials have been completed for deferiprone (an iron chelation treatment) and fosmetpantotenate (precursor replacement therapy). A pilot open‐label trial of pantethine as a potential precursor replacement strategy has also been completed, and a trial of 4‐phosphopantetheine has begun enrollment. Several other compounds have been evaluated in pre‐clinical studies, and additional clinical trials may be anticipated.ConclusionsExperience with these trials has encouraged a critical evaluation of optimal trial designs, as well as the development of PKAN‐specific measures to monitor outcomes. PKAN provides a valuable example for understanding targeted drug development and clinical trial design for rare disorders. © 2021 International Parkinson and Movement Disorder Society

2021-06-01·Movement Disorders1区 · 医学

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration

1区 · 医学

Article

作者: Vanegas‐Arroyave, Nora ; Thakur, Nivedita ; Videnovic, Aleksandar ; Martí, Maria J. ; Jech, Robert ; Correa‐Vela, Marta ; Burns, Colleen ; Bischoff, Almut Turid ; Roze, Emmanuel ; Escolar, Maria L. ; Gonzalez, Victoria ; Greblikas, Feriandas ; Fraser, Jamie L. ; Kmiec, Tomasz ; Zorzi, Giovanna ; Monduy, Migvis ; Lang, Anthony ; Perez‐Dueñas, Belen ; Mercimek‐Andrews, Saadet ; Bonnet, Cecilia ; Hermanowicz, Neal ; Jinnah, Hyder A. ; Cif, Laura ; Tochen, Laura ; Planellas, Lluis ; Klopstock, Thomas ; Pfeiffer, Helle Cecilie Viekilde ; Comella, Cynthia ; Nimmo, Graeme A.M.

AbstractBackgroundPantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments.ObjectivesThe Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression.MethodsThis 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.ResultsBetween 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.ConclusionsTreatment 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.

2020-12-24·Journal of Medicinal Chemistry1区 · 医学

Cyclic Phosphopantothenic Acid Prodrugs for Treatment of Pantothenate Kinase-Associated Neurodegeneration

1区 · 医学

Article

作者: Cicero, Daniel ; Vecchi, Andrea ; Di Marco, Annalise ; Monteagudo, Edith ; Auciello, Giulio ; Ciammaichella, Alina ; Fezzardi, Paola ; Elbaum, Daniel ; Gonzalez Paz, Odalys ; Malancona, Savina ; Harper, Steven ; Bracacel, Elena ; Beconi, Maria ; Rossetti, Ilaria

Mutations in the human PANK2 gene are implicated in neurodegenerative diseases such as pantothenate kinase-associated neurodegeneration (PKAN) and result in low levels of coenzyme-A (CoA) in the CNS due to impaired production of phosphopantothenic acid (PPA) from vitamin B5. Restoration of central PPA levels by delivery of exogenous PPA is a recent strategy to reactivate CoA biosynthesis in PKAN patients. Fosmetpantotenate is an oral PPA prodrug. We report here the development of a new PANk2^-/- knockout model that allows CoA regeneration in brain cells to be evaluated and describe two new series of cyclic phosphate prodrugs of PPA capable of regenerating excellent levels of CoA in this system. A proof-of-concept study in mouse demonstrates the potential of this new class of prodrugs to deliver PPA to the brain following oral administration and confirms incorporation of the prodrug-derived PPA into CoA.

100 项与 Fosmetpantotenate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10934	-	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
泛酸激酶相关神经变性	临床2期	挪威	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	德国	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	意大利	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	加拿大	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	波兰	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	法国	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	捷克	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	西班牙	Travere Therapeutics, Inc.	2017-07-17
泛酸激酶相关神经变性	临床2期	美国	Travere Therapeutics, Inc.	2017-07-17

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03041116 (Pubmed \| Mov Disord) 人工标引	临床3期	泛酸激酶相关神经变性	84	Fosmetpantotenate	蓋製網築鹽遞襯鏇繭憲(衊築鑰壓蓋鹹襯壓遞襯) = 獵夢鏇襯壓繭選糧窪繭鬱齋鏇窪鏇鑰憲積窪夢 (糧膚遞窪鏇觸齋襯鹽憲, 11.4) 更多	不佳	2021-06-01
				Placebo	蓋製網築鹽遞襯鏇繭憲(衊築鑰壓蓋鹹襯壓遞襯) = 齋壓選衊餘範網壓鹹糧鬱齋鏇窪鏇鑰憲積窪夢 (糧膚遞窪鏇觸齋襯鹽憲, 11.5) 更多
NCT03041116 (PKAN, CTgov)	临床3期	泛酸激酶相关神经变性	84	Fosmetpantotenate (Fosmetpantotenate)	齋夢壓醖鬱蓋夢餘簾願(顧觸獵齋膚壓構觸簾遞) = 衊繭淵鏇製壓窪窪廠廠淵壓選築糧齋淵築衊顧 (構憲醖遞顧醖齋壓獵醖, 製糧憲醖簾蓋製衊蓋艱 ~ 鬱糧範顧夢鹽餘壓範衊) 更多	-	2020-12-29
				Placebo (Placebo)	齋夢壓醖鬱蓋夢餘簾願(顧觸獵齋膚壓構觸簾遞) = 餘鏇顧顧鏇蓋壓鏇構窪淵壓選築糧齋淵築衊顧 (構憲醖遞顧醖齋壓獵醖, 鑰淵願選夢壓遞淵壓糧 ~ 淵積蓋繭網醖鬱觸製鑰) 更多