A Phase 3, Twelve-week Study to Determine the Efficacy, Safety and Tolerability of P2B001 Once Daily Compared to Its Individual Components in Subjects With Early Parkinson's Disease and to a Calibration Arm of Pramipexole ER.

P2B001 is an investigational drug that comprised of low doses of two drugs, pramipexole and rasagiline, which are both approved drugs and routinely used in standard therapy for Parkinson's disease. The two drugs work in two different mechanisms that help each other, so there is a reason to believe that their combined activity will be better than each individual drug, and that lower doses can be used without losing the therapeutic effect. Thus, the development of P2B001 is intended to provide a combination of low doses of these two drugs, in an improved formulation, that is hoped to be more effective in controlling Parkinson's disease symptoms and with less side effects than each of the drugs taken alone or the current available commercial drugs taken together. In a previously completed clinical trial a significant improvement in Parkinson's disease symptoms was seen in patients treated with P2B001 compared to patients that were treated with placebo.
In this phase 3 study , the safety and efficacy of P2B001 will be assessed by comparing P2B001 to its individual components pramipexole and rasagiline. This will be done by monitoring the motor and non-motor symptoms, evaluating responses participants provide on questionnaires relating to Parkinson's disease and quality of life that will be completed on every visit. In addition, this study will also compare P2B001 to a marketed drug of pramipexole ER. Approximately 525 patients will participate in this research study and the participation in this study will last between 14 to 18 weeks.

开始日期2018-01-19

申办/合作机构

Pharma Two B Ltd.

NCT01968460 / Completed临床2/3期

A Phase 2B, Twelve-week Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease

This study will evaluate an oral fixed-dose, once daily product that combines pramipexole and rasagiline for the treatment of early Parkinson's disease.
Animal studies support the therapeutic advantage of combining low doses of rasagiline and pramipexole and suggest further improvement when both are administered in a sustained fashion. Both rasagiline and pramipexole are well known marketed drugs for Parkinson's disease with a good safety profile. combining the drugs in low doses and controlled release may provide better symptom management than the existing drugs alone or together.

开始日期2013-12-01

申办/合作机构

Pharma Two B Ltd.

100 项与盐酸普拉克索/甲磺酸雷沙吉兰相关的临床结果

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100 项与盐酸普拉克索/甲磺酸雷沙吉兰相关的专利（医药）

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项与盐酸普拉克索/甲磺酸雷沙吉兰相关的文献（医药）

2024-02-01·Movement disorders : official journal of the Movement Disorder Society

A Randomized Phase 3 Study Comparing P2B001 to its Components (Low‐Dose Extended‐Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended‐Release Pramipexole in Early Parkinson's Disease

Article

作者: Kieburtz, Karl ; Hauser, Robert A ; Kreitzman, David L ; de Marcaida, Joy Antonelle ; Burdick, Daniel J ; McGarry, Andrew ; Gil, Ramon A ; Olanow, C Warren ; Dhall, Rohit ; Elmer, Lawrence W

Abstract:

Background:

There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.

Objectives:

The objective was to determine if P2B001 (a fixed, low‐dose, extended‐release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole‐ER.

Methods:

This was a 12‐week, double‐blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole‐ER 0.6 mg or rasagiline‐ER 0.75 mg), or commercial doses of pramipexole‐ER titrated to optimal dose (1.5–4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole‐ER.

Results:

P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were −2.66 (95% CI, −4.33 to −1.00) versus pramipexole‐ER 0.6 mg (P = 0.0018) and − 3.30 (95% CI, −4.96 to −1.63) versus rasagiline‐ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole‐ER (mean, 3.2 mg), but significantly less worsening in daytime‐sleepiness (ESS treatment difference: −2.66 [95% CI, −3.50 to −1.81]; P < 0.0001). P2B001 was well‐tolerated with fewer sleep‐related and dopaminergic adverse events than titrated doses of pramipexole‐ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects.

Conclusions:

P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole‐ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once‐daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.

2022-05-01·Advances in therapy3区 · 医学

P2B001 (Extended Release Pramipexole and Rasagiline): A New Treatment Option in Development for Parkinson’s Disease

3区 · 医学

Review

作者: Oren, Sheila ; Hauser, Robert A ; Friedman, Hadas ; Giladi, Nir ; Brotchie, Jonathan ; Poewe, Werner ; Litman, Pninit

Despite levodopa's superior efficacy in reducing the motor symptoms of Parkinson's disease (PD), its risk to induce motor complications requires consideration of the pros and cons of initiating treatment with levodopa-sparing strategies. The current drive toward early levodopa monotherapy is primarily driven by safety and tolerability concerns with dopamine agonists and only mild efficacy of other available approaches. Recently, P2B001, a novel once-daily combination of low-dose, extended-release formulations of pramipexole and rasagiline (0.6 mg and 0.75 mg respectively), has entered clinical development. In this drug evaluation, we review the preclinical and current clinical data for P2B001 and its components. The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa.

2017-05-01·Movement disorders : official journal of the Movement Disorder Society1区 · 医学

A randomized trial of a low‐dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease

1区 · 医学

Article

作者: Friedman, Hadas ; Klepiskaya, Olga S. ; Kreitzman, David L. ; Litman, Pninit ; Kieburtz, Karl ; Leinonen, Mika ; Linvah, Nurit ; Hauser, Robert A. ; Russell, David S. ; the P2B Study Group, for ; Giladi, Nir ; Kadosh, Shaul ; Olanow, C. Warren ; Lew, Mark F. ; Elmer, Lawrence

ABSTRACT:

Background:

Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo‐controlled study to determine whether 2 doses of a novel slow‐release, low‐dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD.

Methods:

Previously untreated patients with early PD were randomized (1:1:1) to once‐daily treatment with P2B001 (0.3 mg pramipexole/0.75 mg rasagiline), P2B001 (0.6 mg pramipexole/0.75 mg rasagiline) or placebo in a 12‐week multicenter double‐blind, placebo‐controlled trial. The primary endpoint was the change from baseline to final visit in Total‐UPDRS score versus placebo. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in Parkinson Disease Quality of Life Scale–39 and UPDRS activities of daily living and motor scores.

Results:

A total of 149 participants were randomized and 136 (91.3%) completed the study. Adjusted mean change from baseline to final visit versus placebo in Total‐UPDRS score was −4.67 ± 1.28 points for the P2B001 0.6/0.75 mg group (P = .0004) and −3.84 ± 1.25 points for the 0.3/0.75 mg group (P = .003). Significant benefits were also observed for both doses in the responder analysis (P = .0002 and P = .0001), Parkinson Disease Quality of Life Scale–39 scores (P = .05 and P = .01), and the UPDRS motor (P = .02 and P = .006) and activities of daily living (P = .005 and P = .0004) subscores. Adverse events of P2B001 were comparable to placebo apart from transient nausea and somnolence, which were more common with P2B001 treatment.

Conclusions:

项与盐酸普拉克索/甲磺酸雷沙吉兰相关的新闻（医药）

2024-03-14

·Insight数据库

再落一子，MNC 巨头「豪赌」CNS 领域

又一巨头出手中枢神经系统（CNS）新药领域。3 月 11 日，勃林格殷格翰与 Sosei Heptares 宣布达成合作，双方将共同开发和商业化治疗精神分裂症的潜在 FIC 药物 GPR52 激动剂疗法，交易总金额超 7 亿欧元。就在几个月前，艾伯维和 BMS 两大跨国制药巨头接连加码，一个月内达成了两项高额收购项目。其中，艾伯维以 87 亿美元收购神经科学公司 Cerevel，将治疗精神分裂症、帕金森病以及情绪障碍等多种疾病的潜力候选药物收入囊中；BMS 更是斥资 140 亿美元收购 Karuna，后者的核心产品 KarXT 已于 2023 年 9 月在美申报上市，PDUFA 目标日期为今年 9 月 26 日，有望成为 50 年来用于治疗精神分裂症的首个新机制药物。MNC 巨头频频出手，CNS 领域为何有如此大的吸引力？国产药企又在这一领域中扮演着怎样的角色？MNC 巨头的算盘精神分裂症，只是中枢神经系统疾病的其中一个分支，其他还有阿尔茨海默症、帕金森病、抑郁症、偏头痛等诸多适应症。以精神分裂症为例，据世界卫生组织统计，全球约 2400 万人患精神分裂症。2022 年，中国精神分裂症患病人数达到约 824.9 万例，预计 2030 年将达到 918.2 万例。庞大的患者人数，带来了较为可观的市场前景。根据 expertmarketresearch 测算，全球精神分裂症药物的市场规模有望于 2023 年的 81.8 亿美金增长至 2032 年的 129.7 亿美金，年复合增长率为 5.4%。市场增速受限制，在于当前极度缺乏疗效和安全性俱佳的抗精神病新式药物，与巨大未被满足的临床需求相矛盾。未来随着更多新式药物获批上市，市场空间必将更大。中国抗精神分裂药物市场有望逐步扩容数据来源：Frost&Sullivan，国泰君安证券研究除市场潜力大外，企业的战略规划和显著的药物优势，也是吸引 MNC 巨头频频落子的重要原因。就艾伯维而言，除了贡献收入「大头」的免疫学、肿瘤业务，神经科学也是其主要聚焦的疾病领域之一，尤其 2023 年以 18.2% 的同比增速贡献了 77.17 亿美元收入，是众多业务中唯一实现正增长的。这得益于多款重磅药物的正向增长，其中精神分裂症药物 Vraylar（卡利拉嗪）销售额达 27.59 亿美元，同比增长 35.4%，是艾伯维神经科学业务收入排行前列的「重磅炸弹」；3 款偏头痛药物 Botox、Ubrelvy、Qulipta 分别实现收入 29.91 亿美元、8.15 亿美元、4.08 亿美元，帕金森病药物 Duodopa 销售额为 4.68 亿美元。精神科学业务表现亮眼，再加上其他业务板块的下滑，尤其 Humira（修美乐）面临专利悬崖危机、「药王」神话不再，此时选择加码 CNS 领域自然是水到渠成的事情。无独有偶，BMS 也有它的「苦恼」，虽然 2023 年核心产品 O 药销售额达到 100 亿美元，却要面临专利到期问题。为了延长其生命周期，除拓展更多适应症外，还把中国 10 个省份的销售权交给再鼎医药。此外，BMS 还选择「买买买」、持续发力 BD 业务，其中最负盛名的便是以总价 140 亿美元现金收购 Karuna，拿下精神分裂症新式药物 KarXT，以及以最高可达 84 亿美元引进百利天恒潜在 FIC 的 HER3/EGFR 双抗 ADC 产品 BL-B01D1。对于勃林格殷格翰而言，这已经不是第一次布局 CNS 领域。现有管线中，就有一款新型 Gly-T1 抑制剂 Iclepertin（BI-425809），正在开展 Ⅲ 期临床试验，预计 2025 年 1 月读出数据。此前，FDA 基于良好的 Ⅱ 期试验结果（登记号：NCT02832037），授予 Iclepertin 治疗精神分裂症的突破性疗法认定。在 CNS 领域尝到了「甜头」，自然更有信心加码这一赛道。更何况，此时再大动干戈的挤进众多 MNC 巨头争抢的肿瘤、自免领域，必然要仔细权衡利弊。选择 CNS 领域、实现差异化突破，或许是个明智的选择。下一代抗精神病药集体亮相实际上，在此之前，CNS 领域并非没有 MNC 巨头入局，只是由于发病机制复杂、研发失败率高等原因，过去数十年来折戟的管线高达上百款。目前市场上销售的抗精神病药主要为非典型抗精神病药，即 20 世纪 60 年代-21 世纪初上市的第二代抗精神病药，比如氯氮平、利培酮、布南色林，以及 2002 年至今上市的第三代抗精神病药，例如阿立哌唑、布瑞哌唑、卡利拉嗪。相比第一代抗精神病药，非典型抗精神病药在疗效上有显著的改善，但仍存在一定的副作用，针对阴性症状的治疗也有待提升，而且作用机制主要为多巴胺受体和 5-HT 受体，亟需新机制、新式药物获批上市。抗精神病药分类数据来源：中国新药与临床杂志，药学学报，国泰君安证券研究由于精神分裂症发病机制复杂未明，药企们选择从各个可能的方向进行探索研发。这也让下一代抗精神病药集中亮相，登上了历史舞台。例如，勃林格殷格翰引进 Sosei Heptares 的潜在 FIC 药物 GPR52 激动剂疗法、艾伯维拿下的 Emraclidine、BMS 拿下的 KarXT，均为治疗精神分裂症的新式药物。其中，GPR52 是一种 G 蛋白偶联受体（GPCR），在中枢神经系统和周围组织中都有表达，而 GPR52 激动剂是能够与 GPR52 结合并激活其信号转导通路的小分子化合物，可通过同时解决精神分裂症的全部三组症状（阳性、阴性和认知症状）来改善患者预后。Emraclidine 是一款高度选择性靶向毒蕈碱 M4 的正向变构调节剂（PAM），具有治疗精神分裂症的 BIC 潜力，目前正在开展两项 II 期注册性临床试验。有意思的是，KarXT 也属于毒蕈碱类抗精神病药物，是一种口服 M1/M4 毒蕈碱激动剂，可以改善精神分裂症的三组症状，意味着未来或将与 Emraclidine 展开同类竞技。进度上，KarXT 已率先向美国 FDA 申报上市，如无意外今年将获批，成为 50 年来首个精神分裂症新式药物。有机构预测，2028 年 KarXT 的销售额将达到 28 亿美元。除上述新式药物外，目前也有一些新机制药物备受关注，包括 TAAR1 激动剂、γ-氨基丁酸（GABA）受体激动剂、5-羟色胺（5-HT）受体拮抗剂，以及勃林格殷格翰在研的甘氨酸转运蛋白 1（Gly-T1）抑制剂 Iclepertin 等。例如，住友制药/大冢制药共同研发的 Ulotaront（SEP-363856）就属于 TAAR1 和 5-HT1A 受体双重激动剂，但很遗憾，治疗急性精神分裂症的两项 III 期研究均未达到主要研究终点，目前正在开发用于精神分裂症、广泛性焦虑症和重度抑郁障碍的辅助治疗。从仿到创，步步为营抗精神病药研发之路，道阻且长。基于此，国内药企选择了较为稳妥的布局方式，先在仿制药和改良型新药/创新剂型上「小试牛刀」，这样既不用担忧投入的高额研发费用可能会「石沉大海」，又不会错过百亿赛道，先拿到「入场券」再说。例如，丽珠集团、海正药业、豪森制药等布局了盐酸鲁拉西酮片仿制药；华海药业、恩华药业、康弘药业等布局了阿立哌唑仿制药；豪森药业、齐鲁制药等布局了奥氮平药物。也有一些国产药企选择布局抗精神病新药/创新剂型，比如绿叶制药、京新药业、再鼎医药等。绿叶制药自研的 Rykindo（利培酮缓释微球注射制剂，LY03004）于 2023 年 1 月获 FDA 批准上市，用于治疗精神分裂症成人患者、以及作为单药或作为锂盐或丙戊酸盐的辅助疗法用于双相障碍 I 型成人患者的维持治疗，成为首个在美获批的国产抗精神病药长效针剂。另一款管线即将迎来商业化上市，棕榈酸帕利哌酮缓释混悬注射液（LY03010）为棕榈酸帕利哌酮长效注射剂，每月给药一次，目前在中美两国均已处于上市审评阶段，用于治疗精神分裂症和分裂情感性障碍。绿叶制药中枢神经药物管线资料来源：绿叶制药官网京新药业研发的 1 类新药 JX11502MA 胶囊，是艾伯维 Vraylar（卡利拉嗪）的类似物，二者作用机制相似但结构不同，主要靶点是多巴胺受体及 5-HT 受体，适应症均为精神分裂阴性症状，目前已处于临床Ⅱ期阶段。在 BD 交易盛行的当下，国产药企向海外企业引进突破性的新机制药物，已是司空见惯之事。例如，再鼎医药于 2021 年与 Karuna 签订合作，拿下了 KarXT 在大中华区开发、生产及商业化的权益，目前正在中国开展用于精神分裂症的 III 期桥接注册研究。在帕金森症领域，京新药业与以色列公司 P2B 达成合作，引进了多巴胺受体激动剂药物 P2B001 复方制剂（普拉克索+雷沙吉兰）在中国的独家开发和商业化权益，目前该药正在海外开展Ⅲ期临床试验，国内已进入临床研究阶段。结语：期待在不久的将来，CNS 新药领域能涌现出更多国产药企的身影。参考文献：1. 各家公司的财报、公告、官网；2. 《20230618-京新药业-002020-首次覆盖报告：精神神经领域龙头，创新转型曙光初现》，国泰君安研报；免责声明：本文为外部作者投稿，仅作消息分享，并不构成投资建议，也不代表 Insight 数据库的立场，文章观点仅供分享行业见解，请广大投资者谨慎。封面来源：站酷海洛 Plus编辑：HebePR 稿对接：微信 insightxb投稿：微信 insightxb；邮箱 insight@dxy.cn

并购抗体药物偶联物上市批准

2023-12-26

·药智网

制药巨头剑指第三大疾病市场

MNC巨额并购资产正在赶KPI，杀疯了。12月7日，艾伯维宣布以每股45美元价格现金收购专注于神经科学领域的生物技术公司Cerevel Therapeutics，以囊获Cerevel治疗精神分裂症、帕金森病以及情绪障碍等多种疾病的潜力候选药物，总体价格约为87亿美元。12月22日，BMS宣布以每股330美元现金收购中枢神经系统药物制造商Karuna Therapeutics，瞄准Karuna旗下进入FDA审评程序的精神分裂症药物KarXT（机构预测潜在销售峰值高达60亿美元），交易价值为140亿美元。同月发生的两大并购案，虽然明面上没有任何关系，却在暗面有着千丝万缕的关系，因为他们都剑指一个方向——中枢神经系统（CNS）新药领域，两大巨头在未来大概率将形成正面冲突。01巨头收入囊中的资产有何特点？在艾伯维、BMS各自的一项收购中，我们能够明显发现：Cerevel与Karuna进度最快的核心管线Emraclidine、KarXT均指向精神分裂症，两者将在未来展开激烈的竞争。值得注意的是，两项交易的价值分布有所差异，虽然MNC收购Karuna的价格较Cerevel更高，但Karuna公司大部分价值都集中在KarXT这款已经进入FDA审评阶段的商业化产品；而Cerevel的价值分布分散几大临床资产上，有平台型交易的特征。1）Cerevel说起来Cerevel的诞生历史颇为有趣，其是从辉瑞剥离而出、贝恩资本出资接受而成立，公司处于临床阶段的资产分别包括：精神分裂症&阿尔茨海默症在研药物Emraclidine（II期）、帕金森症在研药物Tavapadon（III期）、癫痫在研药物Darigabat（II期）。几条管线中，又以Emraclidine备受关注，其有潜力成为治疗精神分裂症的Best in class疗法。早在2022年12月公布的Emraclidine精神分裂症Ib期临床显示：Emraclidine展现具备统计学意义的疗效与安全性，支持口服一天一次，不需要剂量滴定，不良反应发生率为52%vs 52%；竞品KarXT在EMERGENT-1试验中AE率为54%vs 43%，口服一天两次且需要剂量滴定。Cerevel进度最快的资产为Tavapadon，有望成为全球首创的D1/D5选择性部分激动剂，其在二期主要临床终点改善运动机能中表现积极，未来有望成为早期帕金森病单一疗法和晚期帕金森病辅助疗法；另一项癫痫药物Darigabat，也将在2024年中期读出二期数据。艾伯维对其的收购在2024年中才能完成，这也是留了一手的表现，等待几项关键临床的结果再最终做决定。Cerevel Therapeutics和艾伯维神经学管线对比图片来源：艾伯维官网2）KarunaKaruna处于临床阶段的资产有两款，一款为已经申报上市的精神分裂症复方药物组合KarXT（通过两款老药有效药物成分的组合），另一款为TRPC4/5抑制剂KAR-2618；不过，KAR-2618是从Goldfinch Bio囊获而来，也就是说公司目前核心自研产品仅有KarXT。目前，Karuna已经向FDA递交了KarXT治疗成人精神分裂症的上市申请，该申请的PDUFA日期为2024年9月26日，如若顺利，KarXT将成为数十年来全新机制的精神分裂症疗法。另外，KarXT还在进行多项适应症探索，包括精神分裂症辅助治疗、阿尔茨海默症等，最快要在2025年后读出数据。图片来源：瞪羚社02肿瘤、自免之后的潜在第三大药物市场：CNS在今年Evaluate评选出最有价值的在研新药TOP10榜单中，令人意外的莫过于头名被默沙东治疗罕见病肺动脉高压的Sotatercept拿到头名，而最火热的肿瘤、自免领域药物则是分别仅拿到了两个、一个席位。中枢神经系统（CNS）疾病药物凭借着礼来阿尔茨海默症新药Donanemab、Karuna精神分裂症药物KarXT的上榜占有两个席位，与肿瘤、代谢并驾齐驱成为上榜药物最多的疾病领域，彰显其黑马潜力。数据来源：Evaluate实际上，过去几十年里由于大量要素的影响，CNS药物市场的潜力被投资者严重低估了。中枢神经系统（CNS）疾病涵盖的适应症非常广阔，包括多发性硬化症（MS）、帕金森病、阿尔茨海默症、精神分裂、抑郁症、偏头痛、睡眠障碍等细分病种；据一项WHO评估显示，全球范围内超过10亿人口饱受CNS疾病困扰。仅以阿尔茨海默症为例，全球患病人数已经高达5000万人，中国更是成为患者人数最多的国家，高达1000万人，且阿尔茨海默症发病率正在逐年提升，预计2050年全球患者将高达1.5亿人。据弗若沙利文统计，2019年全球CNS药物市场规模为1245亿美元（中国市场296亿美元），为第四大药物市场。未来10-15年内，全球和中国CNS药物市场预计保持稳定、快速增长，2034年全球和中国CNS药物市场将分别达到1721亿美元、571亿美元。图片来源：光大证券过去，有效药物的缺乏阻碍了CNS药物市场规模的快速增长，药物缺失的直接原因则是因为研发成功率低下。塔夫茨大学药物开发研究中心一项研究显示：发现FDA最终批准上市的CNS药物的成功率（6.2%）不到非CNS药物批准率（13.3%）的一半；另一项数据显示：中枢神经系统药物研发的成功率却很低，仅有约8%。在拥有大量未满足临床需求和创新药数量稀少的尖锐背景下，这也使得CNS新药成为爆品的几率成倍提升。瑞银预测，阿尔茨海默症药物Donanemab（礼来）、Lecanemab（渤健）销售峰值将分别超过50亿美元、48亿美元；而在多发性硬化症领域，罗氏CD20单抗Ocrevus在2022年全球销售峰值高达64亿美元，而渤健曾经的当家产品Tecfidera（富马酸二甲酯）销售峰值一度达到44亿美元。作为全球第四大药物市场并有望冲击第三名的CNS，其强悍的潜力有望在未来被加速挖掘。03哪些国内药企，提前布局CNS大市场？CNS药物领域，国内的未来还是属于转型升级的老牌药企。据某榜单显示，刨除大学、药物研究所，在研CNS药物最多的企业分别为恩华药业、绿叶制药、恒瑞医药和上海赛默罗生物。名列TOP1的恩华药业，最新数据显示至少有25款在研创新药项目，13款1类新药处于IND及以上阶段。目前，公司引进的TRV130已经在国内获批上市，用于治疗成人患者严重需要注射阿片类药物的急性疼痛，预计销售峰值有望达到20亿；同时公司通过“自研+引入”双轮战略开发CNS药物，已进入临床的药物覆盖精神分裂症、阿尔茨海默症、帕金森症、抑郁症等，进度最快的为依托咪酯升级产品NH600001（临床二期），用于麻醉诱导和短时手术麻醉。绿叶制药是首个实现CNS药物出海的中国药企，其Rykindo（利培酮缓释微球注射制剂）已获得FDA批准用于治疗精神分裂症患者；另外，公司用于治疗精神分裂症急性期和维持期的治疗LY03010（棕榈酸帕利哌酮缓释混悬注射液）已在美国达到关键临床预设终点，有望加速进入海外商业化阶段。另外在研管线方面，绿叶制药拥有超过15款在研中枢神经系统药物管线，其中有大量管线阶段处于临床后期，包括LY3003、LY03010等，适应症涵盖CNS领域的大部分病种。恒瑞医药在CNS领域的在研管线超过10个，以麻醉镇静药物为主，当前该领域核心产品为布托啡诺、右美托咪定、甲苯磺酸瑞马唑仑等。值得注意的是，恒瑞医药CNS管线布局优势集中在疼痛管理、阿尔茨海默症两大领域。恒瑞医药的Aβ单抗SHR-1707是国内进度最快的跟随者，在2023AAIC展示的数据展现出了初步的有效&安全性；在术后疼痛管理领域，公司有四款药物处于临床阶段，覆盖多类手术术后疼痛适应症。除了上述三大老牌药企外，单个或多个CNS产品研发上国内药企也不缺佼佼者，比如先声药业（脑卒中重磅药先必新以及舌下片）、海思科（麻醉镇静新药环泊酚、镇痛药HSK21542）等；并且，国内也企业通过License in方式引进了海外不少重磅药物，如再鼎医药拥有Karuna的KarXT国内权益，京新药业引入了帕金森病潜在重磅药P2B001（海外三期临床达到终点）等。结语：无论研发有多困难，CNS药物市场崛起已是确定性的趋势，不可阻挡。来源 | 瞪羚社（药智网获取授权转载）撰稿 | Kris.责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 张武龙 13368443108（同微信）阅读原文，是昨天最受欢迎的文章哦

并购临床2期申请上市优先审批临床3期

2023-11-09

·BioSpace

Pharma Two B Announces Publication of Positive Phase 3 Study Results of P2B001, an Investigational Treatment for Early Parkinson’s Disease, in Movement Disorders

Demonstrated that P2B001 provides benefits comparable with commercially used doses of marketed pramipexole-ER (PramiER) while minimizing associated daytime sleep–related and dopaminergic side effects associated P2B001 provided superior efficacy on motor symptoms and activities of daily living, compared to each of its individual components The convenient dosing of P2B001, as a no-titration, once-daily single pill, may be a valuable option for patients, neurologists, and particularly non-specialists who are often the only physicians treating PD patients REHOVOT, Israel, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Pharma Two B Ltd., a private, late-stage pharmaceutical company, today announced that data from a Phase 3 study evaluating P2B001, a fixed, low-dose extended-release (ER) combination of pramipexole 0.6 mg and rasagiline 0.75 mg, were published in Movement Disorders. Results from the international, multicenter, randomized, double-blind parallel-group study evaluated the safety and efficacy of P2B001 in patients with early Parkinson’s disease compared to its components and to commercial doses of the dopamine agonist pramipexole (mean 3.2 mg per day). The study included 544 untreated patients with Parkinson’s disease who were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or marketed PramiER individually titrated to optimal dose (1.5-4.5 mg). “The present study demonstrates that each component contributes to the benefits of P2B001, and that it provides benefits comparable to commercially used doses of Pramipexole ER but with a reduced frequency of sleep-related and dopaminergic adverse events," said C. Warren Olanow, M.D., FRCPC, Chairman Emeritus of the Department of Neurology and Professor Emeritus in the Department of Neuroscience at the Mount Sinai School of Medicine in New York City. Further, he stated that “P2B001 is a once-a-day treatment that requires no titration. As such, if approved, P2B001 represents an important consideration for initiating treatment in patients with early PD.” “P2B001 represents a novel and easy-to-use therapeutic approach, as there has been a clear unmet need for a once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sleepiness, a commonly reported side effect among people with PD, often caused by dopamine agonist treatment,1-3” said Robert Hauser, M.D., M.B.A., Director, Parkinson’s Disease & Movement Disorders Center, University of South Florida. The primary endpoint was change from baseline to week 12 in Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III comparing P2B001 to its individual components. The key secondary endpoint was the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of commercially available PramiER. The change from baseline in total UPDRS (primary endpoint) showed that P2B001 was significantly superior to each of its individual components demonstrating that each contributed to the P2B001 benefit. Least squares mean (LSM) (standard error) treatment difference between P2B001 and pramipexole ER (PPX-ER 0.6 mg) was –2.66 ± 0.85 points (p = 0.0018), and between P2B001 and rasagiline ER (RAS-ER 0.75 mg) was –3.30 + 0.85 points (p = 0.0001). The change from baseline to week 12 in total UPDRS score between P2B001 and PramiER (individually titrated to optimal dose; mean, 3.2 mg/day) was not significantly different (–8.35 ± 0.86 vs. 7.98 ± 0.60; p = 0.7197). Analysis of the key secondary endpoint (change from baseline to week 12 in the ESS score) demonstrated no worsening in the sleepiness scale with P2B001 treatment, whereas optimized doses of PramiER (mean dose, 3.2 mg) caused significant worsening in ESS. LSM difference between groups was –2.66 ± 0.43 (p < 0.0001). P2B001 was generally well tolerated and showed fewer sleep-related and dopaminergic adverse events in comparison to commercially used doses of pramipexole ER. "We are grateful to the patients, families and clinicians who have contributed to this study as we look to deliver a new, convenient treatment option for patients with early Parkinson’s disease,” said Dan Teleman, CEO of Pharma Two B. “We look forward to moving P2B001 forward towards an NDA submission to make this potential treatment option available to patients.” About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with Parkinson’s disease. Extended release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for both pharmaceutical composition and method of treatment with P2B001, which are expected to remain in effect until January 2033. About Pharma Two B Pharma Two B is a private, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that may offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. Our company is led by a highly experienced team in Parkinson’s disease, supported by top-tier scientific and clinical key opinion leaders and backed by a dedicated group of investors. For more information, please visit: . Forward-Looking Statements Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,”” “anticipate,”” look forward,” “believe,” “potential,” “propose” and “continue” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. JNeurol Neurosurg Psychiatry. 2017;88(8):653-662. doi:10.1136/jnnp-2016-31502 Suzuki K. Current update on clinically relevant sleep issues in Parkinson’s disease: a narrative review. J Parkinsons Dis. 2021;11(3):971-992. doi: 10.3233/JPD-202425 Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol. 2005;62(8):1242-1248. doi: 10.1001/archneur.62.8.1242 CONTACT INFORMATION Dan Teleman CEO Pharma Two B Ltd. Cell + 972-54-550-0804 Email: dan@pharma2b.com U.S. media contact: Cali Mangel Director Cell: 215-694-1577 Email: Cali.Mangel@calciumco.com

临床结果临床3期

100 项与盐酸普拉克索/甲磺酸雷沙吉兰相关的药物交易

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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	美国	Pharma Two B Ltd.	2018-01-19
帕金森病（青年型、早发型）	临床3期	加拿大	Pharma Two B Ltd.	2018-01-19
帕金森病（青年型、早发型）	临床3期	德国	Pharma Two B Ltd.	2018-01-19
帕金森病（青年型、早发型）	临床3期	西班牙	Pharma Two B Ltd.	2018-01-19

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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


S32.010 (AAN2023)	N/A	帕金森病	-	P2B001 (low dose combination of extended-release pramipexole and rasagiline)	網構鬱淵製衊簾鏇壓鬱(獵願範繭廠餘糧顧膚艱) = 遞膚選鹹鹽壓遞餘襯選簾獵繭鹹願鑰廠壓選襯 (夢膚憲獵憲淵觸廠鑰簾 ) 更多	-	2023-04-25
S32.010 (AAN2023)	N/A	帕金森病	-	Extended-Release pramipexole (Prami-ER)	網構鬱淵製衊簾鏇壓鬱(獵願範繭廠餘糧顧膚艱) = 鏇簾簾夢糧淵獵繭願廠簾獵繭鹹願鑰廠壓選襯 (夢膚憲獵憲淵觸廠鑰簾 ) 更多	-	2023-04-25
NCT01968460 (CTgov)	临床2/3期	帕金森病（青年型、早发型）	149	Placebo	齋構顧膚窪夢衊廠簾壓(鑰鹹膚積鏇遞繭選製顧) = 夢願窪構構選窪選餘網範淵繭積築觸淵製築鏇 (鏇襯糧製糧鬱壓憲壓艱, 廠憲鬱壓觸膚夢網獵繭 ~ 願鹹網窪簾醖顧夢餘夢) 更多	-	2023-04-07