/ -- AbbVie (NYSE: ABBV) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tavapadon, a novel selective dopamine D1/D5 receptor partial agonist that was studied as a once daily oral treatment for Parkinson's disease.

/ -- 艾伯维（AbbVie，纽约证券交易所代码：ABBV）今天宣布，已向美国食品和药物管理局（FDA）提交了 tavapadon 的新药申请（NDA）。Tavapadon 是一种新型的选择性多巴胺 D1/D5 受体部分激动剂，被研究用于每日一次口服治疗帕金森病。

The submission is based on results from the TEMPO clinical development program that evaluated the efficacy, safety and tolerability of tavapadon across a broad Parkinson's disease population. This includes two Phase 3 trials (TEMPO-1 and TEMPO-2) in early Parkinson's disease, and one Phase 3 trial (TEMPO-3) with tavapadon as adjunctive to levodopa in patients experiencing motor fluctuations.

该提交基于 TEMPO 临床开发计划的结果，该计划评估了 tavapadon 在广泛的帕金森病人群中的有效性、安全性和耐受性。这包括两项针对早期帕金森病的 III 期试验（TEMPO-1 和 TEMPO-2），以及一项针对经历运动波动的患者使用 tavapadon 辅助左旋多巴的 III 期试验（TEMPO-3）。

TEMPO-1 and TEMPO-2 demonstrated that patients experienced a statistically significant improvement from baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III combined score at week 26..

TEMPO-1和TEMPO-2试验表明，患者在第26周时，运动障碍协会-统一帕金森病评定量表（MDS-UPDRS）第二部分和第三部分的综合评分较基线有统计学意义上的显著改善。

TEMPO-3 demonstrated that patients experienced more 'on' time, referring to the period when symptoms were well controlled without dyskinesia or involuntary movements.

TEMPO-3 试验表明，患者经历了更多的“开启”时间，这是指症状在没有运动障碍或不自主运动的情况下得到良好控制的时期。

The submission is also based on an interim data cut from TEMPO-4, an open-label extension (OLE) trial to assess the long-term clinical benefit of tavapadon.

该提交还基于 TEMPO-4 的中期数据截取，这是一项开放标签扩展 (OLE) 试验，用于评估 tavapadon 的长期临床益处。

'For many people living with Parkinson's disease, today's oral standard of care isn't effective enough to manage symptoms,' said

“对于许多帕金森病患者来说，当前的口服标准治疗并不足以有效控制症状，”

Roopal Thakkar

鲁帕尔·塔卡尔

, M.D., executive vice president, research and development, chief scientific officer, AbbVie. 'We recognize the physical and mental impact that Parkinson's disease can cause and are committed to providing next-generation treatment options that will help individuals regain motor control and independence at all stages of this challenging disease.' .

医学博士，艾伯维执行副总裁，研发主管，首席科学官。“我们认识到帕金森病可能带来的身体和精神影响，并致力于提供下一代治疗选择，帮助患者在这一具有挑战性的疾病的各个阶段重新获得运动控制和独立性。”

About the TEMPO Clinical Development Program

关于TEMPO临床开发计划

The submission is supported by results from three placebo-controlled studies: TEMPO-1 and -2 enrolled patients with early Parkinson's disease (with or without an MAO-B inhibitor) and TEMPO-3 enrolled patients who are on fixed-dose levodopa and had motor fluctuations. An open-label extension study (TEMPO-4) is ongoing to assess the long-term safety and efficacy of tavapadon through 58 weeks of treatment.

该提交得到了三项安慰剂对照研究的结果支持：TEMPO-1 和 -2 纳入了早期帕金森病患者（无论是否使用 MAO-B 抑制剂），而 TEMPO-3 纳入了接受固定剂量左旋多巴并出现运动波动的患者。一项开放标签扩展研究（TEMPO-4）正在进行中，以通过 58 周的治疗评估 tavapadon 的长期安全性和有效性。

TEMPO-4 enrolled patients who completed participation in TEMPO-1 through 3, as well as patients on stable doses of levodopa who had not been in prior TEMPO trials..

TEMPO-4 招募了已完成 TEMPO-1 至 3 试验的患者，以及未参与过先前 TEMPO 试验但使用稳定剂量左旋多巴的患者。

TEMPO-1 was a Phase 3 double-blind, randomized, placebo-controlled, parallel-group, 27-week trial to evaluate the efficacy, safety and tolerability of two fixed doses of tavapadon in early Parkinson's disease. The primary endpoint was the change from baseline in the MDS-UPDRS Parts II and III combined score.

TEMPO-1 是一项为期 27 周的 III 期双盲、随机、安慰剂对照、平行组试验，旨在评估两种固定剂量的 tavapadon 在早期帕金森病中的疗效、安全性和耐受性。主要终点是 MDS-UPDRS 第 II 和第 III 部分综合评分相对于基线的变化。

Key secondary endpoints included change from baseline in the MDS-UPDRS Parts II score and percentage of responders with 'much improved' or 'very much improved' on the Patient Global Impression of Change (PGIC). A total of 529 adults between the ages of 40-80 were enrolled in the trial. All had a confirmed diagnosis of Parkinson's disease and had disease duration (from time of diagnosis) of less than three years.

关键的次要终点包括MDS-UPDRS第二部分评分相对于基线的变化，以及在患者总体变化印象（PGIC）中被评为“显著改善”或“非常显著改善”的应答者百分比。试验共招募了529名年龄在40至80岁之间的成年人。所有参与者均确诊为帕金森病，且病程（从诊断时起算）少于三年。

Patients were randomized to receive tavapadon titrated to 5 milligrams, tavapadon titrated to 15 milligrams or placebo, orally and once daily..

患者被随机分配接受剂量调整至5毫克的他伐帕酮、剂量调整至15毫克的他伐帕酮或安慰剂，口服，每日一次。

TEMPO-2 was a Phase 3 double-blind, randomized, placebo-controlled, parallel-group, 27-week trial to evaluate the efficacy, safety and tolerability of flexible doses of tavapadon (5-15 mg QD) in early Parkinson's disease. The primary endpoint was the change from baseline in the MDS-UPDRS Parts II and III combined score.

TEMPO-2 是一项 III 期双盲、随机、安慰剂对照、平行组、为期 27 周的试验，旨在评估灵活剂量的他帕多（5-15 毫克每日一次）在早期帕金森病中的疗效、安全性和耐受性。主要终点是从基线到 MDS-UPDRS 第 II 和第 III 部分综合评分的变化。

Key secondary endpoints included change from baseline in the MDS-UPDRS Parts II score and percentage of responders with 'much improved' or 'very much improved' on the PGIC. A total of 304 adults between the ages of 40-80 were enrolled in the trial. All had a confirmed diagnosis of Parkinson's disease and had disease duration (from time of diagnosis) of less than three years.

关键的次要终点包括MDS-UPDRS第二部分评分与基线相比的变化，以及在PGIC上“显著改善”或“非常显著改善”的应答者百分比。试验共纳入了304名年龄在40至80岁之间的成年人。所有参与者均确诊为帕金森病，且病程（从诊断时起算）少于三年。

Patients were randomized to receive tavapadon 5-15 mg QD or placebo, orally and once daily..

患者被随机分配接受每日一次5-15毫克的他瓦帕顿或安慰剂，口服。

TEMPO-3 was a Phase 3 double-blind, randomized, placebo-controlled, parallel-group, flexible-dose, 27-week trial to evaluate the efficacy, safety and tolerability of tavapadon as an adjunctive therapy to LD for advanced Parkinson's disease. Patients were provided with a home diary to assess their motor function status (Hauser diary).

TEMPO-3 是一项为期27周的III期双盲、随机、安慰剂对照、平行组、灵活剂量试验，旨在评估tavapadon作为左旋多巴辅助疗法治疗晚期帕金森病的疗效、安全性和耐受性。患者被提供一份家庭日记以评估其运动功能状态（Hauser日记）。

The primary endpoint was change from baseline in the total 'on' time without troublesome dyskinesia based on the two-day average of the self-completed Hauser diary. Secondary endpoints included change from baseline in total daily 'off' time, change from baseline in total 'on' and 'off' time at earlier timepoints in the trial, and change from baseline in the MDS-UPDRS Part I, II and III scores.

主要终点是基于两天平均的患者自填 Hauser 日记，评估无困扰性运动障碍的总“开”期时间从基线的变化。次要终点包括每日总“关”期时间从基线的变化、试验中较早时间点总“开”和“关”期时间从基线的变化，以及 MDS-UPDRS 第 I、II 和 III 部分评分从基线的变化。

A total of 507 adults between the ages of 40-80 were enrolled in the trial. All had a confirmed diagnosis of Parkinson's disease, were experiencing motor fluctuations and were on a stable dose of LD for at least four weeks prior to screening. Patients were randomized to receive either tavapadon adjunctive to LD, tavapadon titrated to 5-15 milligrams, or placebo and LD, orally and once daily..

共有507名40-80岁的成年人参与了这项试验。所有患者均确诊患有帕金森病，出现运动波动，并在筛查前至少四周内保持稳定的左旋多巴剂量。患者被随机分配接受每日一次口服的左旋多巴联合tavapadon、剂量调整为5-15毫克的tavapadon，或安慰剂和左旋多巴。

The majority of adverse events were non-serious and mild or moderate in severity across TEMPO-1 through 3.

在TEMPO-1至3中，大多数不良事件均为非严重事件，且严重程度为轻度或中度。

The incidence of SAEs and deaths were low and comparable between placebo and tavapadon groups.

SAE 和死亡的发生率较低，在安慰剂组和 tavapadon 组之间具有可比性。

The most common adverse reactions reported in ≥10% of patients were nausea, headache and dizziness for Parkinson's disease patients without levodopa, and nausea and dyskinesia for patients on adjunctive therapy with levodopa.

不使用左旋多巴的帕金森病患者报告的最常见的不良反应为恶心、头痛和头晕，而接受左旋多巴辅助治疗的患者则为恶心和运动障碍。

TEMPO-1:

临时-1:

NCT04201093

NCT04201093

TEMPO-2:

临时-2:

NCT04223193

NCT04223193

TEMPO-3:

节奏-3:

NCT04542499

NCT04542499

TEMPO-4:

临时-4:

NCT04760769

NCT04760769

About Parkinson's Disease

关于帕金森病

More than 11 million people worldwide are living with Parkinson's disease,

全球有一千一百多万人患有帕金森病，

a progressive and chronic neurological disorder characterized by tremor, muscle rigidity, slowness of movement and difficulty with balance.

一种以震颤、肌肉僵硬、运动迟缓和平衡困难为特征的进行性和慢性神经系统疾病。

The motor symptoms of Parkinson's disease begin when approximately 60-80 percent of the dopamine-producing cells in the brain are lost, and symptoms continue to worsen slowly over the course of time.

帕金森病的运动症状在大脑中约60%-80%的多巴胺生成细胞丧失时开始出现，并且症状会随着时间的推移缓慢加重。

As Parkinson's disease progresses, patients experience complications, including motor and non-motor fluctuations and dyskinesia. Patients report switching from an 'on' state (when symptoms are generally well controlled) to an 'off' state, during which symptoms such as tremor and stiffness may reappear and patients have more difficulty moving..

随着帕金森病的进展，患者会经历包括运动和非运动波动以及运动障碍在内的并发症。患者报告称，从“开启”状态（症状通常得到良好控制）切换到“关闭”状态时，震颤和僵硬等症状可能重新出现，并且患者在活动方面会遇到更多困难。

Patients with advanced Parkinson's disease may also experience dyskinesia (involuntary movements) which can significantly hinder daily activities.

帕金森病晚期患者还可能出现异动症（不自主运动），这可能会严重妨碍日常活动。

While there is no known cure for the disease, there are treatments available to help reduce symptoms.

虽然这种疾病尚无已知的治愈方法，但有一些治疗可以帮助减轻症状。

About Tavapadon

关于Tavapadon

Tavapadon is an investigational, novel selective D1/D5 receptor partial agonist that was studied as a once-daily oral medicine for Parkinson's disease for use both with and without levodopa. Tavapadon is not approved by any health regulatory authority.

Tavapadon 是一种研究性新型选择性 D1/D5 受体部分激动剂，作为每日一次口服药物进行研究，用于单独使用或与左旋多巴联合使用治疗帕金森病。Tavapadon 尚未获得任何卫生监管机构的批准。

About AbbVie in Neuroscience

关于AbbVie在神经科学领域

At AbbVie, our commitment to preserving personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of approved treatments in neurological conditions, including migraine, movement disorders, and psychiatric disorders, along with a robust pipeline of transformative therapies.

在艾伯维，我们致力于维护全球神经和精神疾病患者的人格尊严，这一承诺坚定不移。凭借三十余年的神经科学经验，我们目前正提供有意义的治疗选择，并推动未来的创新。艾伯维的神经科学产品组合包括已获批的针对神经疾病的疗法，涵盖偏头痛、运动障碍和精神疾病等领域，同时拥有强大的变革性疗法研发管线。

We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners, and clinicians.

我们已经在研究方面进行了大量投资，并致力于更深入地理解神经和精神疾病。每一个挑战都让我们更加坚定决心，推动我们为受这些疾病影响的患者、护理伙伴以及临床医生发现并提供新的进展。

About AbbVie

关于艾伯维

AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care — and products and services in our Allergan Aesthetics portfolio.

艾伯维的使命是发现并提供创新的药物和解决方案，以解决当今严重的健康问题，并应对未来的医疗挑战。我们努力在几个关键的治疗领域——免疫学、肿瘤学、神经科学和眼科护理——以及我们艾尔建美学产品组合中的产品和服务，对人们的生活产生显著影响。