更新于：2024-11-15

Olanzapine

奥氮平

更新于：2024-11-15

概要

概要

基本信息

简介Zyprexa® 或奥氮平（一种抗精神病药物）广泛用于治疗精神分裂症、双相1型障碍和伴随这些病症的激越。该药物由礼来研发的一种D1受体抑制剂，可有效调节大脑内多巴胺和血清素的水平。自从1996 年获得欧盟初步批准后，奥氮平已成为治疗各种精神障碍的首选药物。它在治疗此类疾病方面的功效已得到充分证明，使其成为精神疾病患者不可或缺的药物。该药物在现代医学中发挥着重要的作用，因为它具有调节脑化学的能力，从而为与精神分裂症和双相情感障碍相关的经常失能的症状提供急需的缓解。

药物类型

小分子化药

别名

2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine、mdc-TJK、Olanzapin

+ [31]

靶点

5-HT2A receptor x 5-HT2C receptor x 5-HT3 receptor x D2 receptor

作用机制

5-HT2A receptor拮抗剂(5-羟色胺2A受体拮抗剂)、5-HT2C receptor拮抗剂(5-羟色胺2C受体拮抗剂)、5-HT3 receptor拮抗剂(5-羟色胺受体3拮抗剂)

治疗领域

神经系统疾病其他疾病

在研适应症

化疗引起的恶心和呕吐躁动抑郁症+ [7]

非在研适应症

神经性厌食症边缘性人格障碍重度抑郁症+ [4]

原研机构

Eli Lilly & Co.

在研机构

齐鲁制药有限公司

CHEPLAPHARM Arzneimittel GmbHApotex Europe BV

+ [13]

非在研机构

Viatris, Inc.Cipla (EU) Ltd.Mylan Pharmaceuticals, Inc.

+ [1]

最高研发阶段批准上市

首次获批日期

欧盟 (1996-09-27),

躁郁症躁狂精神分裂症

最高研发阶段(中国)批准上市

特殊审评优先审评 (中国)

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结构

分子式C17H20N4S

InChIKeyKVWDHTXUZHCGIO-UHFFFAOYSA-N

CAS号132539-06-1

关联

536

项与奥氮平相关的临床试验

NCT06554613 / Not yet recruiting临床2期IIT

An Open-label, Two-arm, Multicenter, Phase II Randomized Controlled Trial Assessing the Impact of Olanzapine on the Efficacy of First-line Immunotherapy in Patients With Advanced EGFR Mutation-negative Non-small Cell Lung Cancer (NSCLC).

Clinical Trial
The objective of this clinical trial is to determine whether antidepressant medications, such as olanzapine, in combination with immune checkpoint inhibitors are more effective than the use of immune checkpoint inhibitors alone. The main questions it aims to answer are:
Is the combination therapy of antidepressant medication with immune checkpoint inhibitors more efficacious than the therapy with immune checkpoint inhibitors alone? What medical issues might participants encounter when treated with the combination of antidepressant medication and immune checkpoint inhibitors?
Participants will:
Take olanzapine in combination with immune checkpoint inhibitors or immune checkpoint inhibitors alone for 2 months.
Visit the clinic for check-ups and tests every two weeks, and have follow-up visits every six weeks after the treatment ends.
Keep a record of their symptoms and disease progression.

开始日期2024-12-01

申办/合作机构

南昌大学第二附属医院

CTRI/2024/09/074067 / Not yet recruiting临床3期IIT

Evaluation of efficacy and safety of add-on olanzapine plus pregabalin versus add-on aprepitant to ondansetron in preventing nausea and vomiting in patients undergoing highly emetogenic chemotherapy: A randomized, double-blind, add-on active-controlled, group-sequential and non-inferiority clinical trial - NIL

开始日期2024-11-01

申办/合作机构-

NCT06588413 / Not yet recruiting临床3期IIT

Randomized, Double-Blind Study of FOND (Fosaprepitant, ONdansetron, Dexamethasone) Plus Either Olanzapine 2.5 Mg Versus 5 Mg for the Prevention of Chemotherapy Induced Nausea and Vomiting in Patients Receiving High-dose Melphalan Conditioning: the FONDO-LOW Study

Patients who receive a chemotherapy called melphalan are at high risk of having nausea and vomiting. A medication called olanzapine has been shown to decrease nausea and vomiting after chemotherapy. A previous research study found the 10 mg dose of olanzapine (combined with 3 standard medications used routinely to prevent nausea/vomiting) to be effective for patients who received melphalan chemotherapy, but several other studies have shown many patients have a side effect of sleepiness (e.g., sedation) with that dose of the medication. Our study will compare two lower doses of olanzapine (5 mg and 2.5 mg) in combination with the 3 standard medications used to prevent nausea/vomiting in the patients who receive melphalan chemotherapy to determine which dose is effective in preventing nausea and vomiting with the lowest amount of sleepiness side effect.

开始日期2024-10-01

申办/合作机构

Augusta University

100 项与奥氮平相关的临床结果

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100 项与奥氮平相关的转化医学

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100 项与奥氮平相关的专利（医药）

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9,268

项与奥氮平相关的文献（医药）

2025-01-01·AMERICAN JOURNAL OF EMERGENCY MEDICINE

Comparing the cardiorespiratory safety of parenteral olanzapine and benzodiazepines to parenteral haloperidol/droperidol and benzodiazepines in emergency department patients

Article

作者: Miller, Christopher D ; Meola, Gregory ; Miller, Christopher D. ; Darko, William ; Bradley, Katherine ; Feldman, Elizabeth A. ; Seabury, Robert ; Feldman, Elizabeth A ; Schrader, Joshua

INTRODUCTION:

This study sought to assess the cardiorespiratory safety of parenteral olanzapine and benzodiazepine combination treatment compared to parenteral droperidol or haloperidol and benzodiazepine combination treatment.

MATERIALS AND METHODS:

This was a retrospective chart review conducted in adult emergency department patients who received intramuscular (IM) or intravenous (IV) droperidol, haloperidol, or olanzapine within one hour of IM or IV benzodiazepine. Patients were stratified into groups based on whether they received either olanzapine in combination with a benzodiazepine (n = 48) or droperidol or haloperidol in combination with a benzodiazepine (n = 48).

RESULTS:

Patients in each group had a decrease in their systolic blood pressure (SBP) after IM/IV olanzapine and IM/IV droperidol or haloperidol when used in combination with an IM/IV benzodiazepine ((Olanzapine + benzodiazepine (mmHg), median (IQR): Pre-SBP: 132 (117-151) vs. Post-SBP: 117 (99-131), p < 0.01) (Droperidol or haloperidol + benzodiazepine (mmHg), median (IQR): Pre-SBP: 138 (122-149) vs. Post-SBP: 106 (98-127), p < 0.01)). Both groups had similar percent SBP decreases post-combination treatment (Olanzapine + benzodiazepine (15.6 %) vs. Droperidol or haloperidol + benzodiazepine (15.2 %); p = 0.55). We did not observe any statistically significant between group differences for hypotension (Olanzapine + benzodiazepine: 1/48, 2.1 % vs. Droperidol or haloperidol + benzodiazepine: 3/48, 6.3 %; p = 0.62)), escalation in oxygen requirements (Olanzapine + benzodiazepine: 7/48, 14.6 %) vs. Droperidol or haloperidol + benzodiazepine: 5/48, 10.4 %; p = 0.76)), or intubation due to cardiorespiratory depression (Olanzapine + benzodiazepine: 0/0, 0 % vs. Droperidol or haloperidol + benzodiazepine: 0/0, 0 %; p = 1.00)).

CONCLUSION:

This study found decreases in SBP after administering parenteral olanzapine and parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine. The percent change in SBP and the frequency of hypotensive episodes post-combination treatment were not different between groups. There were also no differences between groups in need of increased oxygen requirements post-combination treatment or need for intubation due to cardiorespiratory depression. This study suggests parenteral olanzapine in combination with a parenteral benzodiazepine may have comparable cardiorespiratory safety versus parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine when treating agitation in the adult ED.

2025-01-01·ARCHIVES OF GERONTOLOGY AND GERIATRICS

Prevalence of strong anticholinergic use in residents with and without cognitive impairment and frailty: Analysis from 106 nursing homes in 12 Asia-Pacific and European countries

Article

作者: Visvanathan, Renuka ; Aalto, Ulla ; Martínez-Velilla, Nicolás ; Liau, Shin J ; Ll, Li ; Roitto, Hanna M ; Onder, Graziano ; Zhang, Tiange G ; Saarela, Riitta ; Li, Li ; Gutiérrez-Valencia, Marta ; Cross, Amanda J ; Bell, J Simon ; Zhao, Meng ; Roncal-Belzunce, Victoria ; Petrie, Kate ; Dowd, Laura A ; Jadczak, Agathe D ; Hamada, Shota ; Ooi, Choon Ean ; Liperoti, Rosa ; Pitkälä, Kaisu ; Villani, Emanuele R ; Sakata, Nobuo

PURPOSE:

There is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty.

METHODS:

Secondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0-2 (non-frail), 3-6 (frail) and 7-14 (most-frail). Data were analyzed using descriptive statistics.

RESULTS:

Overall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %).

CONCLUSIONS:

One in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm.

2025-01-01·TALANTA

Fabrication of a molecularly imprinted polymer-based electrochemical sensor for the selective assay of antipsychotic drug clozapine and performance comparison with LC-MS/MS

Article

作者: Kaya, S. Irem ; Al, Selen ; Budak, Fatma ; Kul, Aykut ; Kaya, S Irem ; Cetinkaya, Ahmet ; Sagirli, Olcay ; Ozkan, Sibel A. ; Ozkan, Sibel A

Clozapine (CLO) is an atypical antipsychotic drug indicated for the treatment of schizophrenia. The treatment effectiveness of CLO is better than that of other atypical antipsychotics, and it has the advantage of being able to determine its effectiveness by measuring its concentration in the patient's blood. Thus, sensitive, selective, and accurate determination of CLO in blood is highly significant for treatment monitoring. This study describes the design and fabrication of a molecularly imprinted polymer (MIP)-based electrochemical sensor for CLO determination. This is the first MIP-based electrochemical application in the literature for CLO determination. Employing the thermal polymerization approach, the MIP was formed on the glassy carbon electrode (GCE) using CLO as the template, trans-3-(3-Pyridyl)acrylic acid (3,3-TA) as the functional monomer, and the support of zinc oxide nanoparticles (ZnO NPs). Elaborate characterizations in terms of surface morphology and electrochemistry were performed via scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) methods. An indirect approach was employed to determine CLO in standard solution, real human biological samples, and tablet formulation, using 5 × 10^-3 M [Fe(CN)₆]^3-/4- solution as the redox probe. The limit of detection (LOD) values for the standard solution and serum sample were calculated as 2.9 × 10^-11 M and 6.01 × 10^-12 M, respectively. These values and recovery studies confirmed the sensor's sensitivity and feasibility. The measurements in the presence of similarly structured compounds (olanzapine and quetiapine fumarate) verified the sensor's superior selectivity. Moreover, the developed sensor's performance was compared and verified using an LC-MS/MS method using the student's t-test and F-test.

276

项与奥氮平相关的新闻（医药）

2024-11-14

·药通社

这么好的品种，不多了！

扫描下方二维码限时免费报名布瑞哌唑片，已经是“卷”得最快的品种了。 6月28日，原研大冢制药的布瑞哌唑片刚在国内上市，7月10日，科伦就申请了仿制上市，后续10多家企业迅速跟进，截至11月14日，已累计20家企业进行了申报，全部为化药4类。其中，哈三联的申请已经被驳回了，大概率是资料没交全。图| 布瑞哌唑片上市申请情况数据源| 摩熵医药从这20家的申报速度，足可以看出：各大立项部门肯定都在关注，就等着参比上市之后立马申报。若审批顺利，批量获批之后，估计此品种立马就会被纳入集采。布瑞哌唑片属于抗精神病药，抗精神病治疗用药全部品类医院端销售额加起来有接近百亿，虽然由于销量最高的奥氮平片和利培酮片先后被纳入了集采，整体销售额正在缓慢下降。但比起卷到地板价的抗高血压药还是要强上许多，毕竟抗高血压药23年全适应症用药销售额才15亿。图| 抗精神病药市场销售数据图源| 摩熵医药像这样的品种不多了。因此，卷的才这么快、这么猛。当然，卷的不只是片剂，也带到了其他剂型。含布瑞哌唑成分共三大剂型，片剂、口崩片、口溶膜，全都有企业布局。和片剂相似，其他两个剂型也全都是等原研上市之后集中申报。目前口崩片和口溶膜原研仍未上市。但布瑞哌唑片成功上市，已经证明了其临床有效性和安全性，其他剂型的审批按理会宽松许多。口崩片方面，首家申报的同样是科伦。科伦于7月9日提交上市申请，以化药3类申报，仅做了BE试验。截止目前已有5家企业上市申请被受理。图：布瑞哌唑口崩片上市申请情况数据源：摩熵医药口溶膜方面，首家申报的依然是科伦。与口崩片同一天，以化药2.2类申报，也是仅做了BE实验。图：布瑞哌唑口溶膜上市申请情况数据源：摩熵医药抗精神病药中有两个口溶膜——奥氮平口溶膜和阿立哌唑口腔膜，均以化药2.2类申报。化药2.2一般都需要大临床，但口溶膜比较特殊，已上市的口溶膜均未进行大临床就获批了. 不需要进行大临床就能获批一个改良型新药，确实很香。因此，近些年开始关注口溶膜的企业越来越多。不过据行业人士透露：口溶膜很难证明自身临床价值，基本很难获批。事实上，这段时间确实已经有多家企业口溶膜产品被驳回或主动撤回。截至目前，最后一个获批的口溶膜是力品药业的阿立哌唑口溶膜，自其获批上市的 10个月以来，至今无一家口溶膜品种获批。布瑞哌唑口溶膜能否上市也未可知，不敢武断进行怀疑。毕竟科伦和齐鲁这样的大公司都上报了，不知是与CDE进行了沟通，还是仅抱着试一试的态度。三个剂型，片剂竞争太多，口溶膜又非常难批，口崩片似乎成了更好的选择。若能顺利获批，优势会更大。口崩片相较于片剂的优势在于对吞咽困难患者不需要水就可给药，对于急性发作的精神病患者来说服用更方便，在抗精神病药中有多个口崩片，比如利培酮口崩片和阿立哌唑口崩片。利培酮口崩片和阿立哌唑口崩片申报上市时也只进行了BE试验，在抗精神病领域，口崩片可以减轻患者的抵触情绪，也可避免患者口腔藏药等，还是有一定临床优势的。销售情况也很可佳。根据摩熵医药数据，利培酮口崩片仅3家上市，2023年医院全终端年销售额就达到了4.5亿，甚至已超过利培酮片的销售额。 3家企业分4.5亿，口崩片的竞争还算小。再看回科伦。三个剂型，科伦全部布局，且都是头一家。可见，科伦非常看好这个成分。除此之外，科伦还立项了一个布瑞哌唑长效注射剂，但仅到临床默示许可阶段，也没有别的企业跟进，再次感叹科伦是准备把布瑞哌唑这个成分全方位布局一遍了。不止是科伦，仔细看会发现，布瑞哌唑三大剂型，齐鲁都紧跟着科伦进行了申报。且两家企业每个剂型的上市受理时间都仅相隔十天。虽然这三个剂型都暂无一家获批，但是竞争的风暴早早就开始酝酿了。现在就看，这三大品种评审是否顺利了，哪家又能获得首仿？投稿/内容沟通：华籍美人（Ww_150525）好品种不多见，更多的好品种尽在↓ 已报名部分参会企业扫描下方二维码限时免费报名大会议程 *上下滑动查看议程 12月3日 MAH政策与监管论坛 09:00-09:30 新政对医药产业的影响及应对张自然中国化学制药工业协会特邀副会长 09:30-09:50 海南省生物医药产业政策解读海南省工业和信息化厅 09:50-10:20 海南省B证许可及监管政策解读药监老师 10:20-10:40 茶歇 10:40-11:20 海南省B证现场检查缺陷及案例分析药监老师 11:20-12:00 药品上市后变更备案及申报案例药监老师 12月3日 MAH&CXO实操论坛 14:00-14:40 MAH制度下，药品全生命周期质量风险管理谭宏宇国家药品GMP专家，原CFDA骨干检查员 14:40-15:10 MAH制度下受托生产企业遴选和审核实践黄小枫华益药业质量受权人 15:10-15:40 优质项目批文发布环节 15:40-16:00 茶歇 16:00-16:30 港澳中成药注册政策解读及行业机遇吕鹏举广东省药品审评中心特聘专家 16:30-17:10 MAH制度下B证体系搭建叶非深圳华润九新药业有限公司质量总监 12月4日 MAH立项与合作论坛 09:00-09:40 现阶段医药企业产品立项与合作中的政策挑战及应对耿鸿武清华大学老科协医疗健康研究中心，执行副主任 09:40-10:20 MAH制度下产品立项及案例（GLP-1为例）赵忠卫深圳奥祺生物医药有限公司总经理 10:20-10:40 茶歇 10:40-11:20 以患者为中心的药品商业化 11:20-12:00 B证公司——站在十字路口戴文杰逍药圈主理人 12月4日 MAH&CXO实操论坛 14:00-14:40 MAH制度下，如何高效开展受托产品的技术转移毕瑞凤资深GMP专家 14:40-15:20 药品许可上市持有人药物警戒实践 15:20-16:00 药品委托生产共线风险评估与防控任老师国家药品GMP检查员 12月3日仿制药/改良新药立项论坛 09:00-09:50 新形势下仿制药企业的战略布局与产品线规划郭新峰南京循证生物科技有限公司创始人 09:50-10:20 无菌原料药制备在改良新药研发中的关键作用冯胜昔广州艾奇西医药科技有限公司创始人、总经理 10:20-10:40 茶歇 10:40-11:20 中药改良型新药选题策略石森林浙江中医药大学教授、浙江省中药复方制剂现代化工程中心主任 11:20-12:00 集采下仿制药的立项策略陈洪千金药业研究院院长 12月3日药物递送技术论坛 14:00-14:40 微球注射剂规模化生产的技术挑战与应对方案周峰中国科学院宁波材料技术与工程研究所研究员 14:40-15:20 各类药物溶出方法在制剂研发中的应用及案例分析段云剑深圳市华溶分析仪器有限公司技术总监 15:20-15:40 茶歇 15:40-16:20 药物制剂新技术及新辅料的产业化 16:20-17:00 AI赋能纳米制剂研发王建新复旦大学教授 12月4日外用制剂论坛 09:00-09:40 外用制剂研究思考周建平中国药科大学教授 09:40-10:20 软膏乳膏剂产品开发的产业化关键问题分析盛晓霞杭州领业医药科技有限公司总经理 10:20-10:40 茶歇 10:40-11:20 经皮给药系统产业化开发的关键问题探讨 11:20-12:00 外用半固体制剂体外评价方法研究及产品质量控制徐玉文山东省食品药品检验研究院化学药品室主任 12月4日药物递送技术论坛 14:00-14:40 口腔膜剂的技术瓶颈及解决策略陈芳医药先进制造国家工程研究中心研究员 14:40-15:20 缓控释制剂开发重难点剖析及案例分享梁超峰主任药师、高级工程师、广东省制药工程专委会，广州市控缓释制剂研究中心，广州市药物制剂新型制药技术重点实验室 15:20-16:00 微纳递药系统的创新发展与应用转化李永勇同济大学医学院教授扫描下方二维码限时免费报名

申请上市

2024-11-11

·PRNewswire

NEURELIS TO SHARE CLINICAL STUDY DESIGN INSIGHTS FOR INVESTIGATION OF VALTOCO® (DIAZEPAM NASAL SPRAY) IN AGES 2 TO 5 AT CHILD NEUROLOGY SOCIETY ANNUAL MEETING

Presentation highlights study-enrollment challenges and strategies to overcome potential barriers SAN DIEGO, Nov. 11, 2024 /PRNewswire/ -- Neurelis, Inc., today announced a presentation on insights into study design from the enrollment process for the new Stellina study investigating VALTOCO® (diazepam nasal spray) for the treatment of seizure clusters in patients with epilepsy aged 2 to 5 years. This age group is not included in the current indication of treatment of seizure clusters in patients with epilepsy aged ≥6 years. The poster presentation will be given at the 53rd Child Neurology Society Annual Meeting in San Diego, November 11-14th. "Data from clinical studies of repetitive seizures in early childhood are critical to help advance new treatments for a young population with currently limited alternatives," said Adrian L. Rabinowicz, MD, Neurelis Chief Medical Officer. "We are pleased to join the child neurology community and exchange learnings at this year's annual meeting as we focus on improving health outcomes for people with epilepsy." Highlights of the presentation include the identification of study-enrollment challenges and strategies to overcome potential barriers in young patients with treatment-resistant epilepsy. Identified findings may be helpful in designing future protocols. The poster titled "Challenges Associated with Enrolling Pediatric Patients with Treatment-Resistant Epilepsy Aged 2–5 Years in a Clinical Trial and Lessons Learned for Future Trials" will be presented on Tuesday November 12th from 12:30 PM-1:45 PM and 5:30 PM-7:00 PM PT. The mission of the Child Neurology Society is to raise awareness about the importance of child neurologists and the health needs of children with chronic neurological conditions. About Neurelis Neurelis, Inc., is a neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and neurologic disorders characterized by high unmet medical need. The FDA has approved Neurelis' VALTOCO® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual's usual seizure pattern in adult and pediatric patients 6 years of age and older. VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL®, a transmucosal absorption enhancement technology that enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. For more information on VALTOCO, please visit . For the latest scientific information on VALTOCO, please visit . Neurelis is also developing NRL-1004, an investigational, Phase 1 stage intranasal olanzapine for treatment of acute agitation episodes associated with schizophrenia and bipolar disorder. In addition, Neurelis is also developing NRL-1049 (previously known as BA-1049), an investigational, Phase 1 new chemical entity Rho kinase (ROCK) inhibitor, for the treatment of cerebral cavernous malformations (CCMS), a rare disorder of the central nervous system (CNS). For more information on Neurelis, please visit . Important Safety Information about VALTOCO: Indication VALTOCO® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older. Contraindications: VALTOCO is contraindicated in patients with: Hypersensitivity to diazepam Acute narrow-angle glaucoma Central Nervous System (CNS) Depression Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits. The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner. Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior. Glaucoma Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma. Neonatal Sedation and Withdrawal Syndrome Use of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly. Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol–preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known. Adverse Reactions The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort. Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance. To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (). Please read full Prescribing Information , including Boxed Warning. Contacts: Brittany Bradrick, Chief Operating Officer and Chief Financial Officer, +1 858 251 2100 SOURCE Neurelis, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准临床1期

2024-11-08

·医药魔方Pro

明星药物KarXT开发团队“新冒险”——挑战CNS药物难题 | Seaport Therapeutics

创新是生物医药领域发展的命脉。如何将一项创新技术、一个创新靶点转换为一类创新疗法是科学界、产业界、投资界共同探讨的命题。医药魔方《创星》栏目，根据InvestGO®独有的评分系统，筛选最值得关注的一批“创新之星”，从科学基础、技术优势、研发潜力等多个维度，洞悉新锐公司获资本青睐的原因，同时，也将总结同领域的全球竞争概况，辅助国内创新药同行的决策判断。 2024年9月26日，治疗精神分裂症的创新药物KarXT成功获FDA批准上市。这款药物的问世标志着精神分裂症领域几十年来的重大突破，它采用了全新的作用机制，不依赖传统的多巴胺或5-羟色胺通路，而是作用于中枢神经系统的毒蕈碱乙酰胆碱受体（mAChR）。KarXT由呫诺美林（xanomeline，M1和M4型mAChR激动剂）和曲司氯铵（trospium，外周mAChR拮抗剂）组成，巧妙的复合设计使KarXT在中枢神经系统激活mAChR的同时，又能控制其引起的外周副作用。KarXT在临床上的亮眼表现引起多家MNC的关注，最终在2023年12月，其原研公司Karuna Therapeutics被BMS以140亿美元的价格并购，成为2023年交易额排名第二的并购案例。而就在该交易达成4个月后，孵化Karuna Therapeutics的PureTech Health宣布成立新公司Seaport Therapeutics，开始一场新的冒险。Seaport Therapeutics和Karuna Therapeutics一样专注于中枢神经系统（CNS）药物研发。来源：Seaport Therapeutics官网 Daphne Zohar担任Seaport Therapeutics的创始人兼首席执行官，她之前担任PureTech Health的创始人兼首席执行官并共同创立了Karuna Therapeutics。Daphne Zohar是一位成功的企业家，从16岁时就开始创业，能够敏锐洞察事物的潜在价值。自创立PureTech Health以来，她为公司带来巨大价值。PureTech Health采用的“Hub and Spoke”经营模式使其能够高效推进研发，目前已开发出了28种疗法，在研产品一部分作为内部管线进行开发，另一部分由PureTech Health成立新的实体公司来推进，如Karuna Therapeutics、Seaport Therapeutics。PureTech Health及其成立的实体公司进行的临床试验80%都取得成功，大约是行业平均水平的6倍。 Daphne Zohar（来源：Seaport Therapeutics官网）另一位联合创始人是Karuna Therapeutics前首席执行官、前首席科学官Steven Paul，在加入Karuna Therapeutics之前，Paul曾担任礼来的研发总裁，负责监督奥氮平（Zyprexa）、度洛西汀（Cymbalta）、xanomeline等CNS药物的开发。在他任职礼来期间，xanomeline已经显示出最初的抗精神病和促认知特性。此外，他还联合创立多家CNS领域的创新药物公司，如Sage Therapeutics等，是CNS药物发现和开发领域的权威专家。 Steven Paul（来源：Seaport Therapeutics官网） Seaport Therapeutics不仅汇聚了Karuna Therapeutics的领导团队，还获得了Karuna Therapeutics投资者的支持。2024年4月9日，其宣布完成1亿美元A轮融资，由ARCH Venture Partners、Sofinnova Investments、Third Rock Ventures和PureTech Health共同领投，其中ARCH、Sofinnova和Third Rock都是Karuna Therapeutics的投资者。10月21日，Seaport Therapeutics又完成2.25亿美元B轮融资，A轮投资者继续跟投。半年狂揽3.25亿美元融资，或许是其与Karuna Therapeutics同样的模式及领导团队，让投资人产生了信任。当然，Seaport Therapeutics的技术平台和管线也同样亮眼。公司的核心技术平台Glyph™，源自澳大利亚莫纳什大学Christopher Porter教授及其研究团队的开创性工作。这一平台的独特之处在于它的药物递送机制：通过直接靶向淋巴系统，绕过传统口服药物必须经历的肝脏首过代谢过程，从而显著提高药物的生物利用度、减少潜在的肝脏毒性并提高患者的整体耐受性。Glyph™平台的设计灵感来源于人体对膳食脂肪的自然处理方式，通过将药物与膳食脂肪分子可逆地结合，形成一种新型前药，这种设计允许药物在口服后随同脂肪分子一起绕过肝脏，直接进入肠道的淋巴管系统。Porter研究团队及其合作者在多个顶尖学术期刊上发表了关于Glyph™平台的研究成果，包括Nature Metabolism、Angewandte Chemie和Journal of Controlled Release。这些研究成果详细阐述了Glyph™平台如何通过淋巴系统实现对药物的有效递送，以及这一技术在不同疗法中的应用潜力，证明了该平台的科学严谨性。 Glyph™平台（来源：Seaport Therapeutics官网） Glyph™平台除了科学研究支持，在临床上也得到了验证。Seaport Therapeutics围绕Glyph™设计了多条管线，且管线具有两个特点，一是聚焦患者需求高度未得到满足的领域，二是优先考虑经过临床疗效验证的药物，利用Glyph™技术实现口服并提高生物利用度、降低副作用等。通过这种方式，Seaport Therapeutics能够快速推进管线进展，填补患者需求。管线情况（来源：Seaport Therapeutics官网） Seaport Therapeutics目前主要推进3条管线，其中进展最为迅速的是SPT-300，这是一种别孕烷醇酮（allopregnanolone）口服前药，处于Ⅱ期临床试验阶段，用于治疗产后抑郁、焦虑症、重度抑郁症等。别孕烷醇酮是γ-氨基丁酸-A（GABAA）受体调节剂，具有经临床验证的快速抗抑郁和抗焦虑活性。2019年，Sage Therapeutics研发的布瑞诺龙（brexanolone，人工合成的别孕烷醇酮）获批上市，是FDA首个批准用于治疗产后抑郁症的药物。但它存在过度镇静和意识丧失的风险，因此必须在获得认证的医疗保健中心，留院观察60小时并在加强监护下静脉给药，这无疑给产后抑郁患者的治疗带来了不便。为了改善这一状况，Sage Therapeutics在2023年推出了另一款针对产后抑郁的口服药物珠兰诺隆（zuranolone），通过对别孕烷醇酮进行结构上的优化解决了口服问题，但它仍然面临着肝脏毒性和首过代谢带来的挑战。此外专注于解决药物口服问题的Lipocine也在尝试利用其技术平台开发可口服的别孕烷醇酮，可能也同样面临这些挑战。值得一提的是，Steven Paul曾是Sage Therapeutics的联合创始人，对于布瑞诺龙和珠兰诺隆的开发以及公司其他管线都做出了重要贡献，因此对于别孕烷醇酮的前药开发或许更有经验和见解。SPT-300的Ⅰ期试验结果显示其耐受性良好，别孕烷醇酮暴露量是其他已发表的口服异孕酮数据的9倍，验证了Glyph™平台提高口服生物利用度的能力。在IIa期试验中，SPT-300大大降低了压力诱导的皮质醇水平，治疗焦虑症效果符合预期，且仅有轻微嗜睡的副作用。 SPT-320是阿戈美拉汀的一种新型前药，正准备开展治疗广泛性焦虑症的Ⅰ期临床研究。阿戈美拉汀于2007年上市，可有效治疗广泛性焦虑症和重度抑郁症，且耐受性高。但是其首过代谢高，生物利用度只有约1%，导致一些患者的肝酶增加，需要频繁的肝功能监测。SPT-320使用Glyph™绕过肝脏首过代谢，很有可能降低用药剂量的同时还能提高阿戈美拉汀的有效全身暴露，并且减少对肝功能的损伤以及监护。 SPT-348是一种创新的非致幻性神经原前药，用于治疗情绪和神经精神障碍。非致幻性神经原是CNS药物中的一个新兴领域，通过增强大脑的可塑性来应对这类疾病，同时避免了传统致幻药物可能带来的不良影响。借助于先进的Glyph™技术平台，SPT-348不仅优化了药物的药代动力学特性，还显著提升了其耐受性，这使得它在维持药效的同时，有效地减少了副作用的发生。Seaport Therapeutics在CNS药物领域内积极拓展，除了以上这3条管线，还在开发多个发现和临床前项目。在CNS药物的开发过程中，常常遇到类药性不足或耐受性问题，导致许多有潜力的新型药物未能成功上市，另外尽管有些药物成功上市，但仍然有很多局限性，如给药方式、生物利用度、毒副作用等。面对这些挑战，Seaport Therapeutics的Glyph™平台，展现出了强大的应对能力。Seaport Therapeutics依靠强大的技术平台和优秀的领导团队，极有可能复制KarXT这样的成功案例，为抑郁症、焦虑症以及其他精神疾病的患者带来新的治疗选择和希望。 -上下滑动查看参考资料 - [1]https://karuna-pharmaceuticals.squarespace.com/about [2]https://puretechhealth.com/ [3]https://seaporttx.com/ [4]DOI: 10.1038/s42255-021-00457-w [5]DOI: 10.3389/fphar.2022.879660 [6]DOI: 10.1016/j.jconrel.2021.02.008 创星公司全球 Septerna | Ceptur | Kelonia Sionna | Aspen | Askgene Terremoto | ReCode | CAMP4 Xilis | Dianthus | Aktis | Orna Pretze | Nested | Matchpoint | Vega CARGO | N1 Life | ITM | Genesis Diagonal | Xaira 中国辐联医药 | 瑞石生物 | 阿泰克可瑞生物 | 星奕昂 | 益杰立科迦进生物 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

抗体药物偶联物并购上市批准

100 项与奥氮平相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00454	奥氮平	N05AH03	DB00334

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
化疗引起的恶心和呕吐	日本	CHEPLAPHARM Arzneimittel GmbH	2017-12-25
化疗引起的恶心和呕吐	日本	Eli Lilly & Co.	2017-12-25
躁动	美国	CHEPLAPHARM Arzneimittel GmbH	2009-03-19
抑郁症	美国	CHEPLAPHARM Arzneimittel GmbH	2009-03-19
难治性抑郁症	美国	CHEPLAPHARM Arzneimittel GmbH	2009-03-19
双相情感障碍及相关疾病	中国	Eli Lilly & Co.	2006-01-01
躁郁症1型	美国	CHEPLAPHARM Arzneimittel GmbH	1996-09-30
躁郁症	欧盟	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁郁症	冰岛	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁郁症	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁郁症	挪威	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁狂	欧盟	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁狂	冰岛	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁狂	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
躁狂	挪威	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
精神分裂症	欧盟	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
精神分裂症	冰岛	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
精神分裂症	列支敦士登	CHEPLAPHARM Arzneimittel GmbH	1996-09-27
精神分裂症	挪威	CHEPLAPHARM Arzneimittel GmbH	1996-09-27

未上市

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
实体瘤	临床3期	中国	江苏豪森药业集团有限公司	2020-10-01
呕吐	临床3期	中国	江苏豪森药业集团有限公司	2020-10-01
病理性赌博症	临床3期	美国	Eli Lilly & Co.	2007-02-01
体重增加	临床3期	美国	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	巴西	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	以色列	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	墨西哥	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	波多黎各	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	俄罗斯	Eli Lilly & Co.	2006-11-01
体重增加	临床3期	韩国	Eli Lilly & Co.	2006-11-01

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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


NCT05693935 (SOLARIS, GlobeNewswire) 人工标引	临床3期	精神分裂症	675	TEV-‘749 531 mg	鑰鏇淵齋顧夢艱蓋艱鏇(齋構鏇網艱築衊襯鹹壓) = 艱襯鬱簾選積製遞鹽廠築獵繭積鑰遞醖蓋獵顧 (構齋艱選膚壓獵餘憲廠 ) 更多	积极	2024-09-26
				TEV-‘749 425 mg	鑰鏇淵齋顧夢艱蓋艱鏇(齋構鏇網艱築衊襯鹹壓) = 製壓壓願鹹鑰構壓憲選築獵繭積鑰遞醖蓋獵顧 (構齋艱選膚壓獵餘憲廠 ) 更多
JPRN-jRCTs031210410 (ERICA study (WJOG14320B), ESMO2024) 人工标引	临床2期	药物引起的恶心和呕吐 \| 转移性乳腺癌 HER2 Positive	168	Olanzapine (the delayed phase)	餘選餘壓顧淵餘糧願獵(壓遞鏇觸獵蓋積糧觸鬱) = 積壓壓廠網遞鹽衊襯蓋觸獵窪獵選網顧艱齋衊 (齋膚憲鬱鑰製艱築獵齋 ) 达到更多	积极	2024-09-14
				Placebo (the delayed phase)	餘選餘壓顧淵餘糧願獵(壓遞鏇觸獵蓋積糧觸鬱) = 簾糧夢襯壓鏇願蓋範鹹觸獵窪獵選網顧艱齋衊 (齋膚憲鬱鑰製艱築獵齋 ) 达到更多
ESMO2024	N/A	-	1,933	Olanzapine	鹽憲鬱夢衊範繭鑰繭衊(遞觸壓衊鹹襯鹽獵願範) = 醖鹽獵觸壓窪窪鹹餘夢鏇繭夢觸製遞鹽淵艱糧 (壓製窪鑰獵壓簾製鏇淵 ) 更多	积极	2024-09-14
				No Olanzapine	鹽憲鬱夢衊範繭鑰繭衊(遞觸壓衊鹹襯鹽獵願範) = 齋鏇構鑰襯繭淵壓艱糧鏇繭夢觸製遞鹽淵艱糧 (壓製窪鑰獵壓簾製鏇淵 ) 更多
ATS2024	N/A	糖尿病酮症酸中毒	-	Olanzapine 5mg	糧築淵願製憲醖窪醖顧(顧築廠網襯膚糧遞簾鹹) = Our patient developed classic symptoms of diabetes approximately 2 weeks after she was started on olanzapine for bipolar disorder and was found to have DKA on admission 觸積鏇鹽鑰獵淵繭繭遞 (願鏇網選網襯顧鑰衊鏇 )	-	2024-05-19
NCT05693935 (SOLARIS, NEWS) 人工标引	临床3期	精神分裂症	675	TEV-'749 high dose	範鬱顧廠鑰蓋鹽鹹醖醖(鬱簾選繭鹹淵顧範築糧) = 餘襯憲顧夢顧鏇糧淵簾醖遞觸夢鹹壓廠鹽顧顧 (壓遞願鹹膚鑰壓築淵蓋 ) 达到	积极	2024-05-08
				TEV-'749 medium dose	範鬱顧廠鑰蓋鹽鹹醖醖(鬱簾選繭鹹淵顧範築糧) = 鬱觸積鑰鬱鏇窪衊網餘醖遞觸夢鹹壓廠鹽顧顧 (壓遞願鹹膚鑰壓築淵蓋 ) 达到
NCT02939287 (CTgov)	临床3期	恶心 \| 呕吐	52	80 mg orally on Days 0 (Aprepitant)	築製鹹鹹構鹽築鑰糧夢(淵遞獵衊齋糧壓繭鬱顧) = 糧觸艱築簾襯顧憲鑰憲壓糧餘簾鏇築壓艱製蓋 (選鬱鏇襯淵鹹糧鬱醖簾, 艱糧廠顧築獵獵蓋範衊 ~ 襯餘觸餘築夢鑰淵製衊) 更多	-	2024-01-22
				+2 (Olanzapine)	築製鹹鹹構鹽築鑰糧夢(淵遞獵衊齋糧壓繭鬱顧) = 選顧淵餘襯醖壓憲衊廠壓糧餘簾鏇築壓艱製蓋 (選鬱鏇襯淵鹹糧鬱醖簾, 鏇鹽繭鏇遞憲願齋襯窪 ~ 繭遞壓願積選壓膚網淵) 更多
ESMO_ASIA2023	N/A	乳腺癌	30	Olanzapine 5 mg	膚選夢積積淵鏇積積願(選範夢膚醖遞衊憲衊繭) = 襯膚淵艱獵鹽蓋艱繭鑰獵構艱襯遞膚顧蓋遞觸 (蓋選廠範夢夢積積繭餘 ) 更多	-	2023-12-02
ESMO_ASIA2023	N/A	追加	84	Olanzapine 5 mg plus pregabalin 75 mg	壓遞鏇蓋遞選夢憲膚醖(窪壓鬱醖蓋鹹獵願壓顧) = 獵範網餘餘構蓋願遞齋積遞製衊遞選鏇衊壓窪 (憲襯淵糧壓願鏇鏇鏇艱 )	-	2023-12-02
				Placebo	壓遞鏇蓋遞選夢憲膚醖(窪壓鬱醖蓋鹹獵願壓顧) = 觸鹽淵廠鑰觸憲積製構積遞製衊遞選鏇衊壓窪 (憲襯淵糧壓願鏇鏇鏇艱 )
ESMO2023 人工标引	临床2期	乳腺癌	76	Palonosetron+aprepitant+ olanzapine	簾壓積觸蓋蓋艱願膚積(鬱齋憲窪醖鹽鹹廠鑰餘) = 壓觸鹽餘製遞鑰鹹選窪構夢範製鹽鹹糧蓋鹽淵 (廠膚積觸鬱齋餘鏇蓋壓, 9.4 ~ 27.5) 更多	不佳	2023-10-21
OMEC (ESMO2023)	临床3期	化疗引起的恶心和呕吐	544	Olanzapine (Standard antiemetic prophylaxis)	繭範襯鑰鑰艱顧憲憲構(淵憲鑰願壓簾鏇選選鏇) = 鏇憲齋壓襯憲鹹簾鹹遞鹽蓋觸積鏇窪衊獵願糧 (衊遞襯顧積鬱艱顧鹹顧 ) 更多	积极	2023-10-21
				Standard antiemetic prophylaxis + Olanzapine	繭範襯鑰鑰艱顧憲憲構(淵憲鑰願壓簾鏇選選鏇) = 憲築淵廠醖鹹顧繭鬱壓鹽蓋觸積鏇窪衊獵願糧 (衊遞襯顧積鬱艱顧鹹顧 ) 更多