Safety, tolerability and potential biomarkers of vodobatinib in patients with dementia with Lewy bodies

IF 3.4 3区医学 Q2 CLINICAL NEUROLOGY

Parkinsonism & related disorders Pub Date : 2025-09-07 DOI:10.1016/j.parkreldis.2025.108020

Fernando L. Pagan , Yasar Torres-Yaghi , Michaeline L. Hebron , Barbara Wilmarth , Xiaoguang Liu , Jaeil Ahn , Charbel Moussa

{"title":"Safety, tolerability and potential biomarkers of vodobatinib in patients with dementia with Lewy bodies","authors":"Fernando L. Pagan , Yasar Torres-Yaghi , Michaeline L. Hebron , Barbara Wilmarth , Xiaoguang Liu , Jaeil Ahn , Charbel Moussa","doi":"10.1016/j.parkreldis.2025.108020","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Activation of the tyrosine kinase Abelson (Abl) was suggested in the pathogenesis of neurodegenerative diseases. We investigated the effects of a potent and highly specific Abl kinase inhibitor vodobatinib (K0706) in patients diagnosed with dementia with Lewy bodies (DLB). We determined safety, tolerability and potential biomarkers following oral administration of vodobatinib versus placebo in DLB patients.</div></div><div><h3>Methods</h3><div>Participants were randomized 1:1:1 into vodobatinib 192 mg, or 384 mg or matching placebo in a single-center, double-blind study. Study drug was taken orally once daily for 3 months followed by one-month wash-out.</div></div><div><h3>Results</h3><div>Twenty-nine individuals were enrolled, 3 were women (10.3 %), age 76.3 ± 6 years (mean ± SD). Vodobatinib was safe and well-tolerated and more adverse events were noted in the placebo (56) vs vodobatinib 192 mg (19) or 384 mg (6) groups. The number of falls were reduced in the vodobatinib 192 mg (6) and 384 mg (0) compared to placebo (28) groups. The only potential significant change in cerebrospinal fluid (CSF) biomarkers was Aβ42/Aβ40 in 192 mg vodobatinib (p = 0.0002) and 384 mg (0.0121) compared to placebo. There was no change in homovanillic acid, a biomarker of dopamine level, or other potential CSF and plasma biomarkers of DLB. Exploratory clinical outcomes were not different between baseline and 3 months in vodobatinib compared to placebo.</div></div><div><h3>Conclusions</h3><div>Vodobatinib appears to be safe and tolerated, but larger trials and longer treatment periods are needed to determine its effects on biomarkers and clinical outcomes.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108020"},"PeriodicalIF":3.4000,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Parkinsonism & related disorders","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1353802025007618","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Activation of the tyrosine kinase Abelson (Abl) was suggested in the pathogenesis of neurodegenerative diseases. We investigated the effects of a potent and highly specific Abl kinase inhibitor vodobatinib (K0706) in patients diagnosed with dementia with Lewy bodies (DLB). We determined safety, tolerability and potential biomarkers following oral administration of vodobatinib versus placebo in DLB patients.

Methods

Participants were randomized 1:1:1 into vodobatinib 192 mg, or 384 mg or matching placebo in a single-center, double-blind study. Study drug was taken orally once daily for 3 months followed by one-month wash-out.

Results

Twenty-nine individuals were enrolled, 3 were women (10.3 %), age 76.3 ± 6 years (mean ± SD). Vodobatinib was safe and well-tolerated and more adverse events were noted in the placebo (56) vs vodobatinib 192 mg (19) or 384 mg (6) groups. The number of falls were reduced in the vodobatinib 192 mg (6) and 384 mg (0) compared to placebo (28) groups. The only potential significant change in cerebrospinal fluid (CSF) biomarkers was Aβ42/Aβ40 in 192 mg vodobatinib (p = 0.0002) and 384 mg (0.0121) compared to placebo. There was no change in homovanillic acid, a biomarker of dopamine level, or other potential CSF and plasma biomarkers of DLB. Exploratory clinical outcomes were not different between baseline and 3 months in vodobatinib compared to placebo.

Conclusions

Vodobatinib appears to be safe and tolerated, but larger trials and longer treatment periods are needed to determine its effects on biomarkers and clinical outcomes.

查看原文本刊更多论文

伏多巴替尼在伴路易体痴呆患者中的安全性、耐受性和潜在生物标志物

酪氨酸激酶Abelson （Abl）的激活被认为在神经退行性疾病的发病机制中起作用。我们研究了一种强效且高度特异性的Abl激酶抑制剂vodobatinib （K0706）在诊断为路易体痴呆（DLB）患者中的作用。我们测定了DLB患者口服vodobatinib和安慰剂的安全性、耐受性和潜在的生物标志物。方法在单中心双盲研究中，参与者以1:1:1的比例随机分为vodobatinib 192mg、vodobatinib 384mg或匹配的安慰剂组。研究药物每天口服一次，持续3个月，然后是一个月的洗脱期。结果共入组29例，女性3例（10.3%），年龄76.3±6岁（mean±SD）。Vodobatinib是安全且耐受性良好的，安慰剂组（56）比Vodobatinib 192 mg（19）或384 mg(6)组注意到更多的不良事件。与安慰剂组（28）相比，vodobatinib组(192 mg（6)和384 mg(0)）的跌倒次数减少。脑脊液（CSF）生物标志物的唯一潜在显著变化是，与安慰剂相比，192 mg vodobatinib组（p = 0.0002）和384 mg vodobatinib组（p = 0.0121）的Aβ42/Aβ40。高香草酸（多巴胺水平的生物标志物）或其他潜在的DLB脑脊液和血浆生物标志物没有变化。与安慰剂相比，沃多巴替尼的探索性临床结果在基线和3个月之间没有差异。结论vodobatinib似乎是安全且耐受的，但需要更大规模的试验和更长的治疗期来确定其对生物标志物和临床结果的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Parkinsonism & related disorders 医学-临床神经学

CiteScore

6.20

自引率

4.90%

发文量

292

审稿时长

39 days

期刊介绍： Parkinsonism & Related Disorders publishes the results of basic and clinical research contributing to the understanding, diagnosis and treatment of all neurodegenerative syndromes in which Parkinsonism, Essential Tremor or related movement disorders may be a feature. Regular features will include: Review Articles, Point of View articles, Full-length Articles, Short Communications, Case Reports and Letter to the Editor.