Tavapadon(Tavapadon) - 药物靶点：D1 receptor x D5 receptor_在研适应症：精神运动障碍，帕金森病，帕金森病（青年型、早发型）_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Tavapadon (USAN)

+ [3]

靶点

D1 receptor x D5 receptor

作用机制

D1 receptor激动剂(多巴胺D1受体激动剂)、D5 receptor激动剂(多巴胺D5受体激动剂)

治疗领域

神经系统疾病内分泌与代谢疾病其他疾病+ [1]

在研适应症

精神运动障碍帕金森病帕金森病（青年型、早发型）+ [1]

非在研适应症-

原研机构

Pfizer Inc.

在研机构

Cerevel Therapeutics LLC

非在研机构

Pfizer Inc.

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C19H16F3N3O3

InChIKeyAKQXQLUNFKDZBN-UHFFFAOYSA-N

CAS号1643489-24-0

关联

20

项与 Tavapadon 相关的临床试验

NCT05610189 / Completed临床1期

A Phase 1, Randomized, Multiple-dose, Crossover Trial in Participants With Parkinson's Disease to Evaluate the Clinical Bioequivalence Between Tavapadon Tablets

The primary purpose of the study is to evaluate the bioequivalence (BE) of tavapadon 15 milligram (mg) tablet to 3x5 mg tablets in participants with Parkinson's disease.

开始日期2022-12-15

申办/合作机构

Cerevel Therapeutics LLC

NCT05581823 / Completed临床1期

A Phase 1, Open-label, Fixed-sequence, Crossover Trial to Evaluate the Effects of Cytochrome P450 (CYP) 3A4 Induction by Carbamazepine on the Steady-state Pharmacokinetics of Tavapadon in Healthy Adult Participants

The primary purpose of this study is to evaluate the effect of carbamazepine, a strong CYP3A4 inducer, on the steady-state pharmacokinetics (PK) of tavapadon in healthy adult participants.

开始日期2022-10-19

申办/合作机构

Cerevel Therapeutics LLC

NCT05404542 / Completed临床1期

A Phase 1 Open-label Trial to Evaluate the Pharmacokinetics and Safety Following Single Dose of Tavapadon in Participants With Severe Renal Impairment Compared to Participants With Normal Renal Function

The primary purpose is to assess the effect of renal impairment on the PK of tavapadon following administration of a single oral dose in participants with severe renal impairment relative to age, body weight, and sex-matched participants with normal renal function.

开始日期2022-05-10

申办/合作机构

Cerevel Therapeutics LLC

100 项与 Tavapadon 相关的临床结果

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100 项与 Tavapadon 相关的转化医学

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100 项与 Tavapadon 相关的专利（医药）

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5

项与 Tavapadon 相关的文献（医药）

2024-04-01·CNS & Neurological Disorders - Drug Targets

Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson’s Disease

Review

作者: Bezard, Erwan ; Kozak, Rouba ; Gray, David ; Leoni, Matthew ; Combs, Cari ; Duvvuri, Sridhar

Abstract:Currently, available therapeutics for the treatment of Parkinson’s disease (PD) fail to provide sustained and predictable relief from motor symptoms without significant risk of adverse events (AEs). While dopaminergic agents, particularly levodopa, may initially provide strong motor control, this efficacy can vary with disease progression. Patients may suffer from motor fluctuations, including sudden and unpredictable drop-offs in efficacy. Dopamine agonists (DAs) are often prescribed during early-stage PD with the expectation they will delay the development of levodopa-associated complications, but currently available DAs are less effective than levodopa for the treatment of motor symptoms. Furthermore, both levodopa and DAs are associated with a significant risk of AEs, many of which can be linked to strong, repeated stimulation of D2/D3 dopamine receptors. Targeting D1/D5 dopamine receptors has been hypothesized to produce strong motor benefits with a reduced risk of D2/D3-related AEs, but the development of D1-selective agonists has been previously hindered by intolerable cardiovascular AEs and poor pharmacokinetic properties. There is therefore an unmet need in PD treatment for therapeutics that provide sustained and predictable efficacy, with strong relief from motor symptoms and reduced risk of AEs. Partial agonism at D1/D5 has shown promise for providing relief from motor symptoms, potentially without the AEs associated with D2/D3-selective DAs and full D1/D5-selective DAs. Tavapadon is a novel oral partial agonist that is highly selective at D1/D5 receptors and could meet these criteria. This review summarizes currently available evidence of tavapadon’s therapeutic potential for the treatment of early through advanced PD.

2020-02-19·ACS Chemical Neuroscience3区 · 医学

D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited Dyskinesia Side Effects

3区 · 医学

Article

作者: Kozak, Rouba ; Brevard, Julie ; Trapa, Patrick ; Young, Damon ; Popiolek, Michael ; Fonseca, Kari R. ; Gray, David L.

Parkinson's disease is a progressive neurodegenerative disease characterized by striatal dopaminergic loss. L-DOPA treatment replaces lost dopamine and enables motor function; however, eventually, fluctuating efficacy and side effects associated with its use become challenging for many patients. Here, we demonstrate, in a clinically translatable nonhuman primate model of parkinsonian motor symptoms, that treatment with the partial D1 receptor agonist CVL-751, formerly known as PF-06649751, is just as effective as L-DOPA in enabling movement and reducing disability. Importantly, CVL-751 efficacy is observed with less of the concomitant dyskinesia side effect associated with L-DOPA treatment. Data presented suggest that partial D1 agonists may be an effective and important treatment strategy for the management of Parkinson's patients.

2020-01-01·Therapeutic Advances in Neurological Disorders2区 · 医学

PF-06649751 efficacy and safety in early Parkinson’s disease: a randomized, placebo-controlled trial

2区 · 医学

ArticleOA

作者: Werth, John ; Zhang, Yao ; Riesenberg, Robert ; Gray, David ; Duvvuri, Sridhar

Background: PF-06649751 is a novel, oral, non-catechol-based, D1/D5 dopamine receptor partial agonist under investigation for the treatment of motor symptoms associated with Parkinson’s disease. Methods: A 15-week, phase II, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy and safety of flexible-dose PF-06649751 in subjects with early stage Parkinson’s disease (ClinicalTrials.gov identifier: NCT02847650). Results: Enrollment was terminated early for reasons unrelated to the trial. Overall, 57 subjects received study medication (PF-06649751 = 29; placebo = 28) and 47 completed the study (PF-06649751 = 25; placebo = 22). Despite early termination, the study met its primary endpoint with the PF-06649751 group showing statistically significant improvement from baseline in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score at week 15 compared with placebo. Mean (SE) change in MDS-UPDRS Part III score was −9.0 (1.54) for PF-06649751 and −4.3 (1.65) for placebo. This corresponds to an improvement versus placebo of 4.8 for the PF-06649751 group (two-sided p = 0.0407; 90% CI = 1.0, 8.6). Statistically significant improvement in MDS-UPDRS-III score was also observed at all assessment time points prior to week 15. The safety profile of PF-06649751 was similar to that observed in prior studies, with the majority of adverse events (AEs) reported as mild or moderate. The most common AEs in the PF-06649751 group were nausea, headache, dry mouth, somnolence, and tremor. Conclusions: Once-daily dosing of oral PF-06649751 resulted in significant improvement of motor symptoms and was generally well tolerated in subjects with early stage Parkinson’s disease.

71

项与 Tavapadon 相关的新闻（医药）

2024-08-02

·Pharmaceutical Technology

AbbVie acquires Cerevel Therapeutics for $8.7bn

Cerevel will now function as a part of AbbVie. Credit: Valeriya Zankovych / Shutterstock. AbbVie has completed its acquisition of all outstanding shares of Cerevel Therapeutics in an $8.7bn deal. In December 2023, the companies signed a definitive agreement under which AbbVie agreed to acquire Cerevel for $45 per share in cash. Cerevel focuses on creating therapies to treat neurological and psychiatric disorders. Through this acquisition, AbbVie will bolster its neuroscience portfolio by adding complementary assets from Cerevel’s pipeline. AbbVie CEO Robert Michael stated: “AbbVie’s acquisition of Cerevel strengthens our foundation in neuroscience and positions us to deliver sustainable long-term performance into the next decade and beyond. See Also: Magazine: Left in limbo: when pharma halts rare disease research FDA approves J&J’s multiple myeloma therapy “Our new Cerevel colleagues share our commitment to deliver meaningful change for patients living with neurological and psychiatric conditions. We are excited to welcome the talented Cerevel team to AbbVie.” Cerevel’s pipeline products are aimed at neurological and psychiatric conditions such as Parkinson’s disease, schizophrenia and mood disorders. Emraclidine is an antipsychotic treatment for schizophrenia from Cerevel. This asset operates as a positive allosteric modulator of the muscarinic M4 receptor. It has shown encouraging results in a Phase I study and is nearing the completion of two Phase II trials intended to support registration. Another key asset in Cerevel’s portfolio is tavapadon, a dopamine D1/D5 selective partial agonist for Parkinson’s disease. Currently in Phase III studies, tavapadon has demonstrated potential as both monotherapy and adjunctive treatment. A Phase III trial met its primary endpoint, with additional data from ongoing trials expected in the second half of 2024. The acquisition also brings CVL-354, a kappa opioid receptor antagonist targeting major depressive disorder, now in Phase I, and darigabat, an alpha 2/3/5 selective GABAA [γ-aminobutyric acid type A – an inhibitory neurotransmitter] receptor PAM for treatment-resistant epilepsy and panic disorder, currently in Phase II, into AbbVie’s neuroscience pipeline.

临床2期临床结果并购临床3期临床1期

2024-06-27

·生物制药小编

艾伯维帕金森疗法再遭FDA CRL抨击

近日（6月25日），艾伯维宣布已经收到FDA关于该公司帕金森新药ABBV-951上市申请（NDA）的完整回复函（CRL）。事实上这已经不是ABBV-951第一次收到CRL了，在去年3月时，艾伯维收到了FDA针对ABBV-951的NDA的第一份CRL，当时的问题主要涉及ABBV-951用来给药的泵，而现在的问题则出在了第三方制造商。之前出问题的泵帕金森病是一种常见的中老年神经系统退行性疾病，病理改变主要以黑质多巴胺神经元丢失以及α-突触核蛋白聚集体为主，而常见药物左旋多巴虽然能够通过补充脑内的多巴胺水平来帮助患者缓解运动障碍等症状，但无法做到根治，可能随着药效波动伴有明显副作用（例如：开关现象），且并不能逆转疾病的进展。而ABBV-951的思路则是通过皮下注射的泵来维持24小时持续注射，虽然ABBV-951药物本身只是左旋多巴/卡比多巴的前体，但相比传统治疗，胜在药物副作用的减少。在一项关键的3期临床试验M15-736 Study中，使用泵进行持续皮下输注给药的ABBV-951组与口服左旋多巴/卡比多巴组相比，在“开启”（即症状缓解）时间和“关闭”（即出现运动障碍症状）时间方面均表现出显著的优势。这进一步证明了使用泵进行递送的有效性。之前因为泵出问题，让艾伯维推迟了9个月才在去年12月重新递交NDA。但现在艾伯维方面的问题似乎已经解决，问题又出现在了第三方制造商上，严重拖延了ABBV-951上市的进度，可以说较为可惜。艾伯维押注帕金森市场虽然此次面临失利，艾伯维似乎对于帕金森市场相当感兴趣，近年来动作频频。在去年10月以总额6.5亿美元（1.1亿美元预付+4.5亿美元里程碑）收购了Mitokinin公司并获得了PINK1激活剂以治疗帕金森，具体机制是利用PINK1维持线粒体功能的作用来改善帕金森。（有研究表明PINK1的功能丧失与家族性帕金森有关）有趣的是，在递交NDA的去年12月，艾伯维还以87亿美元收购了CNS疾病开发公司Cerevel，这家公司前身是辉瑞的CNS部门，后来被拆分出来通过贝恩资本的注资成为一家公司。该公司目前的核心管线是tavapadon，也是一款帕金森药物，是一款D1/D5部分激动剂。 D1和D5受体属于多巴胺受体家族，分别调控运动控制和认知功能，正常情况下常常会与多巴胺结合，但在帕金森患者中，多巴胺神经元丢失，缺乏多巴胺作用，因此tavapadon与D1/D5受体结合，就可以模拟多巴胺的作用，进而改善帕金森病患者的症状。今年4月发布的关键III期临床数据显示，tavapadon达到了主要终点，与安慰剂相比，在27周内，运动障碍的总“正常”时间有统计学意义上的显著增加。参考来源： https://news.abbvie.com/2024-06-25-AbbVie-Provides-U-S-Regulatory-Update-on-ABBV-951-Foscarbidopa-Foslevodopa

临床3期并购申请上市

2024-06-25

·BioSpace

FDA Again Hits AbbVie Parkinson’s Treatment With Complete Response Letter

Pictured: AbbVie building in Lake Bluff, Illinois/iStock, vzphotos The FDA has again denied AbbVie’s New Drug Application for its ABBV-951 Parkinson’s treatment due to issues with a third-party manufacturer. The pharma announced Tuesday that it received a Complete Response Letter from the regulator. AbbVie emphasized the Complete Response Letter (CRL) did not reveal any issues with the safety or efficacy of ABBV-951 or its administration device, and that the FDA is not requesting that AbbVie conduct additional efficacy and safety trials related to the drug or device-related testing. The FDA’s CRL cited observations from an inspection of the third-party manufacturer’s facility that did not involve any AbbVie medicines, according to the company. “We are focused on working with the FDA to bring this important therapy to patients as soon as possible,” AbbVie CMO Roopal Thakkar said in a statement. ABBV-951 is a solution of two prodrugs—cabidopa and levodopa—and is administered subcutaneously in a 24-hour continuous infusion to treat motor fluctuations in patients with advanced Parkinson’s disease. Approved in over 34 countries, this latest regulatory roadblock is the second for AbbVie in its quest for U.S. approval. In March 2023, the FDA issued the first CRL for AbbVie’s New Drug Application (NDA) for ABBV-951. The issue at the time involved the pump used to administer the infusions and not the drug itself. The regulator requested additional information on the pump as part of its review. AbbVie resubmitted its NDA in December 2023. The company’s next steps in addressing the FDA’s latest rejection were not detailed in Tuesday’s announcement beyond the company’s statement that it is working with the agency to bring the drug to U.S. patients “as quickly as possible.” ABBV-951 isn’t AbbVie’s only potential Parkinson’s treatment seeking approval. After signing a deal to scoop up Cerevel Therapeutics in December 2023 for $8.7 billion, the biopharma reported topline data in April 2024 from a Phase III of tavapadon used in combination with levodopa. The trial endpoint tested the total “on time” for patients, when they can move and function without dyskinesia. The combination provided patients with a nearly three times greater effect than levodopa alone. Cerevel said at the time that the data readout would support regulatory submission. The AbbVie acquisition is expected to close in mid-2024. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

申请上市并购临床3期临床结果

100 项与 Tavapadon 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11431	Tavapadon	-	DB14899

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病（青年型、早发型）	临床3期	法国	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	波兰	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	美国	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	德国	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	捷克	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	乌克兰	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	以色列	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	保加利亚	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	加拿大	Cerevel Therapeutics LLC	2019-12-13
帕金森病（青年型、早发型）	临床3期	西班牙	Cerevel Therapeutics LLC	2019-12-13

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临床结果

适应症

分期

评价

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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


NCT04542499 (TEMPO-3, NEWS) 人工标引	临床3期	帕金森病	-	Tavapadon	(簾鏇製憲製廠鬱範積繭) = Patients treated with tavapadon adjunctive to LD experienced a clinically meaningful increase of 1.1 hours in total “on” time without troublesome dyskinesia compared to those treated with LD and placebo. 餘選廠鹹憲衊鏇顧繭積 (齋願膚範選窪積醖簾壓 ) 达到更多	积极	2024-04-18
NCT02847650 (Pubmed \| Ther Adv Neurol Disord) 人工标引	临床2期	帕金森病	57	PF-06649751	(觸網遞餘夢選餘鬱餘遞) = 鏇繭積夢醖顧簾艱鑰齋壓網顧醖窪網壓選積遞 (壓壓衊憲壓蓋網築齋蓋, 1.54)	积极	2020-03-06
				Placebo	(觸網遞餘夢選餘鬱餘遞) = 獵憲醖積選鏇鑰淵願積壓網顧醖窪網壓選積遞 (壓壓衊憲壓蓋網築齋蓋, 1.65)
NCT03185481 (CTgov)	临床2期	精神运动障碍 \| 帕金森病	5	PF-06649751	糧糧蓋構鑰積鑰夢膚憲(糧製膚鹽繭糧壓製淵齋) = 築遞顧艱餘遞願網糧鏇餘遞夢選憲鬱憲齋構鹽 (窪構餘衊簾積顧積觸淵, 齋蓋襯鬱窪夢醖窪醖簾 ~ 鏇積願鬱衊顧遞鹽淵顧) 更多	-	2019-04-12
NCT02847650 (CTgov)	临床2期	帕金森病（青年型、早发型）	57	PF-06649751 (PF-06649751)	鑰遞壓選築膚齋鏇衊製(壓鬱襯齋範壓願鏇鏇鹹) = 壓醖遞鬱餘憲顧構願鹹齋糧簾壓艱觸膚糧顧鬱 (齋蓋積壓網蓋築糧遞糧, 鑰獵構淵艱選築鹽顧鹽 ~ 鑰壓憲網鑰醖顧簾築壓) 更多	-	2019-01-15
				Placebo (Placebo)	鑰遞壓選築膚齋鏇衊製(壓鬱襯齋範壓願鏇鏇鹹) = 獵夢遞糧鏇淵顧觸襯鬱齋糧簾壓艱觸膚糧顧鬱 (齋蓋積壓網蓋築糧遞糧, 蓋鹹簾淵網鏇餘齋願膚 ~ 醖觸糧壓選窪襯鏇觸膚) 更多
NCT02687542 (CTgov)	临床2期	精神运动障碍 \| 帕金森病	108	Placebo	遞觸範襯憲製齋簾糧選(構鑰網繭蓋膚艱願廠簾) = 願築襯廠艱壓餘窪襯鬱觸觸鏇衊廠觸顧製選遞 (鹹獵憲觸鏇範鹽繭鹽艱, 蓋窪夢遞齋鏇窪餘糧簾 ~ 選構齋憲鑰膚窪觸夢壓) 更多	-	2018-12-24
Pubmed \| Neurol Ther	临床1期	帕金森病	-	PF-06649751	(簾膚夢鹽獵壓齋衊鬱廠) = 製構鹽淵鹽鑰觸襯壓鹽夢積蓋蓋鹽選膚夢窪蓋 (繭艱簾獵鏇餘獵願願鬱 )	-	2018-12-01
				Placebo	(簾膚夢鹽獵壓齋衊鬱廠) = 壓糧蓋構夢蓋顧膚蓋獵夢積蓋蓋鹽選膚夢窪蓋 (繭艱簾獵鏇餘獵願願鬱 )
NCT02224664 (CTgov)	临床1期	精神运动障碍 \| 帕金森病	50	L-Dopa (L-Dopa)	(製遞餘遞膚衊製醖膚獵) = 窪淵襯夢範艱壓壓鹹鏇選簾廠淵醖鹹齋積淵願 (醖膚積願範艱選膚製顧, 獵選夢鏇製淵襯築蓋選 ~ 鹽淵憲襯齋糧簾網憲繭) 更多	-	2017-03-27
				PF-06649751+L-Dopa (PF-06649751 5 mg + L-Dopa)	(製遞餘遞膚衊製醖膚獵) = 獵艱鑰夢築窪顧鏇觸鹹選簾廠淵醖鹹齋積淵願 (醖膚積願範艱選膚製顧, 製糧觸餘願壓築窪餘簾 ~ 憲醖構蓋憲繭遞選窪積) 更多