The Safety Profile of Pridopidine, a Novel Sigma-1 Receptor Agonist for the Treatment of Huntington's Disease.

IF 7.4 2区医学 Q1 CLINICAL NEUROLOGY

CNS drugs Pub Date : 2025-03-07 DOI:10.1007/s40263-025-01171-x

Yigal Paul Goldberg, Leehee Navon-Perry, Andrés Cruz-Herranz, Kelly Chen, Gabriele Hecker-Barth, Katrin Spiegel, Yael Cohen, Martin Niethammer, Andrew M Tan, Henk Schuring, Michal Geva, Michael R Hayden

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引用次数: 0

Abstract

Background: Huntington's disease (HD) is a rare, fatal, chronic progressive neurodegenerative disorder with a significant unmet medical need for effective treatments. Pridopidine is a novel, first-in-class, highly selective and potent sigma-1 receptor (S1R) agonist in development for HD. Pridopidine has been extensively studied in adult HD across the full spectrum of disease severity and age ranges, and its safety profile has been characterized in approximately 1600 participants across multiple studies and a broad range of doses. The specific objective of this study was to gain an in-depth understanding of pridopidine's safety profile at the recommended human dose of 45 mg twice daily (bid) in patients with HD.

Methods: An integrated safety analysis of pooled data from 1067 patients with HD enrolled in four double-blind, placebo-controlled studies was performed. The safety profile of pridopidine was compared with placebo.

Results: Pridopidine was found to be generally safe and well tolerated with an adverse event (AE) profile comparable to that of placebo. Moreover, there were no significant differences observed in the safety profile of pridopidine compared with placebo when analyzed by age, sex, baseline total functional capacity (TFC), cytosine-adenine-guanine (CAG) repeat length, use of antidopaminergic medications (ADMs), and region.

Conclusions: The integrated analysis replicated and corroborated the good safety profile observed in the individual studies. Despite the larger sample size, no new safety signals emerged. Long-term exposure to pridopidine, up to 6.5 years in open-label extension studies, revealed no new safety concerns, supporting its potential for long-term use in patients with HD.

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新型Sigma-1受体激动剂普里哌啶治疗亨廷顿病的安全性研究

背景：亨廷顿舞蹈病（HD）是一种罕见的、致命的、慢性进行性神经退行性疾病，对有效治疗的医学需求尚未得到满足。Pridopidine是一种新型的，一流的，高选择性的，有效的sigma-1受体（S1R）激动剂，正在开发用于HD。Pridopidine已经在成人HD中进行了广泛的研究，涵盖了整个疾病严重程度和年龄范围，其安全性已经在大约1600名参与者中进行了多项研究和广泛的剂量范围。本研究的具体目的是深入了解在HD患者推荐的人剂量为45 mg，每日两次（bid）的普利多定的安全性。方法：对四项双盲安慰剂对照研究中1067例HD患者的汇总数据进行综合安全性分析。将哌啶与安慰剂的安全性进行比较。结果：发现普里哌啶总体上是安全的，耐受性良好，不良事件（AE）概况与安慰剂相当。此外，在年龄、性别、基线总功能容量（TFC）、胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复长度、使用抗多巴胺能药物（ADMs）和地区等方面，与安慰剂相比，哌啶的安全性没有显著差异。结论：综合分析重复并证实了在个别研究中观察到的良好安全性。尽管样本量增加了，但没有出现新的安全信号。在开放标签扩展研究中，长期暴露于哌啶长达6.5年，没有发现新的安全性问题，支持其在HD患者中长期使用的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS drugs 医学-精神病学

CiteScore

12.00

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.