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更新于：2026-07-12
Tominersen
更新于：2026-07-12
概要
基本信息
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)终止 |
特殊审评孤儿药 (美国) |
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结构/序列
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Sequence Code 317419970
来源: *****
关联
6
项与 Tominersen 相关的临床试验NCT05686551
A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen in Individuals With Prodromal and Early Manifest Huntington's Disease
NCT04000594
An Open-Label Adaptive Multiple-Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO7234292 in CSF and Plasma, and Safety and Tolerability Following Intrathecal Administration in Patients With Huntington's Disease
NCT03842969
An Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Intrathecally Administered RO7234292 (RG6042) in Patients With Huntington's Disease
100 项与 Tominersen 相关的临床结果
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100 项与 Tominersen 相关的转化医学
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100 项与 Tominersen 相关的专利（医药）
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16
项与 Tominersen 相关的文献（医药）2026-04-01BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Quantitative relationship between tominersen concentrations in cerebrospinal fluid and biomarker changes in Huntington's disease patients
Article
作者: Sanwald Ducray, Patricia ; Hawellek, David J. ; Grimsey, Paul ; Björnsson, Marcus ; McColgan, Peter ; Silber Baumann, Hanna E. ; Tabrizi, Sarah ; Wild, Edward J. ; Anderson, Karen ; Leavitt, Blair R. ; Yamamoto, Yumi ; Landwehrmeyer, Bernhard G.
Aim:
Intrathecally administered antisense oligonucleotide tominersen aims to slow Huntington's disease progression by lowering mutant huntingtin (mHTT) protein levels. This study used non‐linear mixed effects population pharmacokinetic and pharmacodynamic (PKPD) modelling to characterize the relationship between tominersen concentration in cerebrospinal fluid (CSF) and CSF mHTT reduction. Additionally, the relationship between tominersen CSF exposure and changes in other CSF biomarkers was investigated to understand tominersen's pharmacodynamic profile. Finally, PKPD model simulations were conducted to inform the dose selection in the GENERATION HD2 study.
Methods:
Data from four clinical studies, including 915 participants receiving placebo or tominersen doses (30–120 mg) every 4, 8 or 16 weeks for up to 25 months, were used to develop the PKPD model. The model was utilized to predict tominersen CSF exposure metrics for individual patients in the GENERATION HD1 study for the exposure–response (ER) analysis and to simulate the PK and PD profiles for lower doses.
Results:
An indirect‐response model described the relationship between tominersen CSF concentration and mHTT reduction, estimating a half‐maximal inhibitory concentration (IC
50
) of 4.18 ng/mL. The ER analysis revealed that the highest exposure quartile showed a 54% mHTT reduction at steady state and transient elevations in biomarkers of neuroinjury and inflammation. In contrast, the lowest exposure quartile had a 24% mHTT reduction and a favourable biomarker profile.
Conclusions:
The PKPD model quantitatively confirms the relationship between tominersen exposure and CSF mHTT lowering. The ER analysis suggests that lower tominersen exposure levels may offer a better benefit–risk profile.
2025-12-01Molecular Therapy-Nucleic Acids
Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease
Article
作者: Bale, Kirsten ; Anderson, Christine ; Fan, Jianjia ; Ko, Seunghyun ; Wellington, Cheryl L ; Yung, Andrew ; Hayden, Michael R ; Kozlowski, Piotr ; Pouladi, Mahmoud A ; Caron, Nicholas S ; Ma, Da
Therapies targeting mutant huntingtin (mHTT) reduction in the brain hold promise as disease-modifying treatments for Huntington disease (HD), necessitating biomarkers that accurately reflect treatment response. We evaluated candidate molecular and imaging biomarkers after mHTT reduction in YAC128 HD mice, with equal numbers of males and females per group. At 6 months of age, YAC128 mice received unilateral intracerebroventricular injections of saline or mHTT-lowering antisense oligonucleotide (HTT ASO). Plasma neurofilament light chain (NEFL) and glial fibrillary acidic protein (GFAP) were measured longitudinally from 6 to 12 months. Structural MRI was performed at 6, 9, and 12 months. At study endpoint, we quantified mHTT target engagement in the brain and performed striatal RNA sequencing. Treatment with HTT ASO produced a sustained reduction of mHTT levels throughout the brain for up to 6 months, significantly slowed plasma NEFL increases, and moderately attenuated GFAP elevation. Although mHTT levels inversely correlated with gray and white matter volumes, treatment did not significantly stabilize regional brain atrophy, highlighting an association between mHTT load and neuroanatomical integrity. HTT ASO also partially reversed striatal transcriptome dysregulation and restored oligodendrocyte-specific gene expression. Plasma NEFL, but not brain imaging, emerges as a sensitive and dynamic response biomarker for mHTT-lowering therapies.
2024-09-01Molecular Therapy-Nucleic Acids
Preclinical evaluation of stereopure antisense oligonucleotides for allele-selective lowering of mutant HTT
Article
作者: Taborn, Kristin ; Prakasha, Priyanka Shiva ; Francis, Christopher ; Byrne, Mike ; Kandasamy, Pachamuthu ; Frank-Kamenetsky, Maria ; Upadhyay, Hansini ; Maguire, Abbie ; Jang, Hyun Gyung ; Purcell-Estabrook, Erin ; Dale, Elena ; Yang, Hailin ; Iwamoto, Naoki ; Meena ; Shimizu, Mamoru ; Hu, Xiao Shelley ; Shelke, Juili Dilip ; Yin, Yuan ; Tseng, Wei Chou ; Zhao, Anderson ; Liu, Yuanjing ; Verdine, Gregory L ; Longo, Ken ; Akhtar, Ali ; Metterville, Jake ; Looby, Richard ; Liu, Fangjun ; Kothari, Nayantara ; Lamattina, Anthony ; Pan, Qianli ; Bowman, Keith ; Vargeese, Chandra ; Standley, Stephany
Huntington's disease (HD) is an autosomal dominant disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in one copy of the HTT gene (mutant HTT, mHTT). The unaffected HTT gene encodes wild-type HTT (wtHTT) protein, which supports processes important for the health and function of the central nervous system. Selective lowering of mHTT for the treatment of HD may provide a benefit over nonselective HTT-lowering approaches, as it aims to preserve the beneficial activities of wtHTT. Targeting a heterozygous single-nucleotide polymorphism (SNP) where the targeted variant is on the mHTT gene is one strategy for achieving allele-selective activity. Herein, we investigated whether stereopure phosphorothioate (PS)- and phosphoryl guanidine (PN)-containing oligonucleotides can direct allele-selective mHTT lowering by targeting rs362273 (SNP3). We demonstrate that our SNP3-targeting molecules are potent, durable, and selective for mHTT in vitro and in vivo in mouse models. Through comparisons with a surrogate for the nonselective investigational compound tominersen, we also demonstrate that allele-selective molecules display equivalent potency toward mHTT with improved durability while sparing wtHTT. Our preclinical findings support the advancement of WVE-003, an investigational allele-selective compound currently in clinical testing (NCT05032196) for the treatment of patients with HD.
110
项与 Tominersen 相关的新闻（医药）2026-07-12
临床2期寡核苷酸临床终止
100 项与 Tominersen 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D12013 | - | - | - |
研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 亨廷顿舞蹈病 | 临床3期 | 美国 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 中国 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 日本 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 阿根廷 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 澳大利亚 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 奥地利 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 加拿大 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 智利 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 丹麦 | 2021-03-22 | |
| 亨廷顿舞蹈病 | 临床3期 | 法国 | 2021-03-22 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 12 | (Dose Level 1 of RO7234292 (RG6042)) | 夢憲衊鏇廠糧齋憲壓餘(鏇淵餘窪壓蓋醖遞糧壓) = 壓蓋獵鬱網窪廠襯鑰糧 襯鏇憲鹽鏇鹽鬱製齋範 (醖衊廠窪鹽鹽遞壓鏇壓, 71400) 更多 | - | 2024-10-03 | ||
(Dose Level 2 of RO7234292 (RG6042)) | 夢憲衊鏇廠糧齋憲壓餘(鏇淵餘窪壓蓋醖遞糧壓) = 憲窪廠觸鹹觸範顧鹹選 襯鏇憲鹽鏇鹽鬱製齋範 (醖衊廠窪鹽鹽遞壓鏇壓, 132000) 更多 | ||||||
临床2期 | 46 | (RO7234292 Monthly) | 構簾築範蓋鏇觸鏇糧餘 = 齋窪襯齋願繭觸餘鑰淵 淵鬱鹽齋淵簾襯衊襯網 (築夢夢襯築築築獵蓋憲, 襯鹹衊選憲衊構範鑰築 ~ 夢範築襯襯膚糧選願鏇) 更多 | - | 2021-01-19 | ||
(RO7234292 Bimonthly) | 構簾築範蓋鏇觸鏇糧餘 = 鑰鬱衊積顧齋網壓鏇網 淵鬱鹽齋淵簾襯衊襯網 (築夢夢襯築築築獵蓋憲, 積網鑰遞襯齋膚築觸遞 ~ 願壓餘鏇廠餘廠廠觸遞) 更多 | ||||||
临床1/2期 | 46 | Placebo (Placebo) | 餘觸願繭範顧衊範鏇鹽 = 餘鏇構鹽憲衊餘獵選鹽 築鬱築簾衊範製襯壓鏇 (淵遞觸淵襯網網繭製築, 壓壓齋鏇範遞鏇蓋窪窪 ~ 襯壓網膚餘憲鬱壓廠艱) 更多 | - | 2019-05-31 | ||
(ISIS 443139 10 mg) | 餘觸願繭範顧衊範鏇鹽 = 餘襯簾繭構餘淵網構繭 築鬱築簾衊範製襯壓鏇 (淵遞觸淵襯網網繭製築, 築觸膚醖獵網衊築遞繭 ~ 顧艱鹹簾鹽廠鏇淵鏇遞) 更多 |
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