A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 24-Week, Phase 2 Study of Two Doses of EVP-6124 Hydrochloride or Placebo in Subjects With Mild to Moderate Alzheimer's Disease Currently Receiving Memantine Medication With or Without Additional Acetylcholinesterase Inhibitor Co-Medication

The purpose of this study is to evaluate the safety of 2 fixed doses of EVP-6124 hydrochloride (HCl) compared to placebo for 24 weeks in subjects with mild to moderate Alzheimer's disease who are concurrently receiving stable treatment with memantine and currently receiving stable treatment or previously treated with an acetylcholinesterase inhibitor.

开始日期2015-07-01

申办/合作机构

FORUM Pharmaceuticals, Inc.

[+1]

NCT02327182

/ Terminated临床3期

A Long-Term Safety Study of MT-4666 in Patients With Mild to Moderate Alzheimer's Disease (AD)

The objective of this study is to evaluate the safety and efficacy of 2 fixed dose of MT-4666 administered once daily for 52 weeks with or without receiving a concomitant acetylcholinesterase inhibitors (AChEIs), in patients with mild to moderate Alzheimer's Disease (AD).

开始日期2014-12-01

申办/合作机构

Mitsubishi Tanabe Pharma Corp.

NCT02004392

/ Terminated临床3期

A 26-Week Extension Study of the Safety and Clinical Effects of EVP-6124 in Subjects With Alzheimer's Disease Currently or Previously Receiving an Acetylcholinesterase Inhibitor Medication

This is a 26-week, randomized extension of the Phase 3 double-blind placebo-controlled studies, EVP-6124-024 and EVP-6124-025. In this extension study, subjects who complete study EVP-6124-024 or EVP-6124-025 and fulfill all entry criteria will be randomized to receive EVP-6124 for an additional 26 weeks.

开始日期2014-06-01

申办/合作机构

FORUM Pharmaceuticals, Inc.

100 项与 Encenicline Hydrochloride 相关的临床结果

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100 项与 Encenicline Hydrochloride 相关的转化医学

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100 项与 Encenicline Hydrochloride 相关的专利（医药）

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项与 Encenicline Hydrochloride 相关的文献（医药）

2024-09-01·PHARMACOPSYCHIATRY

Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments

Review

作者: Hori, Satoko ; Hart, Xenia ; Takahashi, Yuna ; Komatsu, Yuki ; Takehara, Moe ; Ueno, Fumihiko ; Uchida, Hiroyuki

Abstract:

Introduction Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. Methods A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. Results Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. Discussion Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

2024-04-01·Neurotoxicity research

Molecular Docking Analysis at the Human α7-nAChR and Proliferative and Evoked-Calcium Changes in SH-SY5Y Cells by Imidacloprid and Acetamiprid Insecticides

Article

作者: Aguayo, Luis ; Guzman-Vallejos, Marcelo S ; Ballaz, Santiago J ; Ramirez-Cando, Lenin J

Acetamiprid (ACE) and Imidacloprid (IMI) are widely-used neonicotinoid insecticides (NNIs) with functional activity at human acetylcholine nicotinic receptors and, therefore, with putative toxic effects. The objective of this study was the evaluation of the interactions between NNIs and α7-nAChR, as this receptor keeps intracellular Ca2+ ([Ca2+]i) to an optimum for an adequate neuronal functioning. Possible interactions between NNIs and the cryo-EM structure of the human α-7 nAChR were identified by molecular docking. Additionally, NNI effects were analyzed in neuroblastoma SH-SY5Y cells, as they naturally express α-7 nAChRs. Functional studies included proliferative/cytotoxic effects (MTT test) in undifferentiated SH-SY-5Y cells and indirect measurements of [Ca2+]i transients in retinoic acid-differentiated SH-SY-5Y cells loaded with Fluo-4 AM. Docking analysis showed that the binding of IMI and ACE occurred at the same aromatic cage that the specific α-7 nAChR agonist EVP-6124. IMI showed a better docking strength than ACE. According to the MTT assays, low doses (10-50 µM) of IMI better than ACE stimulated neuroblastoma cell proliferation. At higher doses (250-500 µM), IMI also prevailed over ACE and dose-dependently triggered more abrupt fluorescence changes due to [Ca2+]i mobilization in differentiated SH-SY5Y neurons. Indeed, only IMI blunted nicotine-evoked intracellular fluorescence stimulation (i.e., nicotine cross-desensitization). Summarizing, IMI demonstrated a superior docking strength and more robust cellular responses compared to ACE, which were likely associated with a stronger activity at α-7nAChRs. Through the interaction with α-7nAChRs, IMI would demonstrate its high neurotoxic potential for humans. More research is needed for investigating the proliferative effects of IMI in neuroblastoma cells.

2021-10-26·Current pharmaceutical design

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for their Use as the Add-on Therapy in Schizophrenia

Review

作者: Coveñas, Rafael ; Werner, Felix-Martin

Background::

Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders, and in this case, they can be treated with clozapine. Based on the previous reviews on novel antipsychotic drugs, it is important to know whether the add-on therapy with the new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score.

Objective::

The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of the currently available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life.

Results::

The mechanisms of action, the therapeutic effects, and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole, and lumateperone have been updated. Published case reports of patients with treatment-resistant psychoses have also been discussed in this study. These patients were treated only with clozapine, as a result of which a high PANSS total score was observed. Only the add-on therapy with cariprazine improved the score, and above all, the negative schizophrenic symptoms and cognitive functions were improved. For the ensurance of a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs might be a choice for the maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, have been investigated in preclinical and clinical trials.

Conclusion::

In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by the add-on therapy with cognitionenhancing drugs.

项与 Encenicline Hydrochloride 相关的新闻（医药）

2025-10-30

·CNSight

阿尔茨海默病新药研发的多靶点探索

阿尔茨海默病（AD）新药研发关键靶点阿尔茨海默病（AD）作为痴呆主要诱因，正成为21世纪健康难题。全球现约2500万-3000万患者，2040年预计增至三倍，且现有治疗多为对症，无法根治。近期《Acta Pharmaceutica Sinica B》综述梳理AD新药研发关键靶点，为攻克疾病提供方向。 AD病理特征与现有治疗局限 AD于1907年由神经学家Alois Alzheimer发现，以进行性认知衰退为主，早期轻度记忆障碍，后期丧失交流能力，还伴语言问题、冲动行为。核心病理是细胞外β-淀粉样蛋白（Aβ）老年斑沉积与细胞内tau蛋白构成的神经原纤维缠结，二者致突触和神经元丢失、大脑萎缩。 AD按遗传分家族性（FAD）和散发性（SAD），按发病时间分早发型（EOAD）和晚发型（LOAD）。发病风险因素多，包括自噬缺陷、衰老、APOE4基因、Trem2基因、生活方式、微生物群改变、心血管疾病、脑外伤及教育水平、高血压、肥胖等。目前FDA已批准的AD治疗药包括：3种乙酰胆碱酯酶（AChE）抑制剂（多奈哌齐、卡巴拉汀、加兰他敏）和1种NMDA受体拮抗剂（美金刚）。它们仅短期改善认知，无法阻病情进展。AChE抑制剂通过抑制乙酰胆碱降解提脑内浓度，NMDA受体拮抗剂减少谷氨酸过度激活致的钙内流、减轻神经损伤，但均不针对AD根本病理。除此之外，FDA还批准了3种Aβ单抗类药物：阿杜卡单抗、仑卡奈单抗、多奈单抗。图2.示意性地描述了AD的乙酰胆碱释放周期和胆碱能假说图3.FDA批准用于治疗AD的药物的二维结构图4.全新NMDA受体拮抗剂的结构图5.谷氨酸在健康大脑中的传播经典靶点：β-淀粉样蛋白（Aβ）相关策略 Aβ异常代谢是AD核心病理，围绕其研发药物有抑制聚集、金属螯合剂、抗Aβ免疫疗法、调控分泌酶等方向。抑制Aβ聚集 Aβ易聚集形成寡聚体、纤维和斑块，可溶性寡聚体神经毒性最强。现有两种聚集抑制剂进入临床：司来吉兰（ELND005）：低剂量（250mg）安全但疗效欠佳，高剂量引发感染甚至死亡，需进一步评估。曲美普拉明：III期试验对认知评分无显著影响，重新分析发现其前药ALZ-801对ApoE4纯合子患者有益。此外，表没食子儿茶素-3-没食子酸酯（EGCG）因多生物活性，正考虑开展AD患者III期试验。图6.淀粉样蛋白聚集抑制剂的结构已扩展临床试验金属螯合剂 AD患者脑内铝、锌、铁、铜等金属离子升高，促Aβ聚集和神经毒性，金属螯合剂可结合这些离子抑Aβ积累。去铁胺（DFO）：两年研究显示，用药患者大脑新皮质铝浓度低，行为能力改善，还可能螯合锌、铜。氯喹诺尔：APP转基因小鼠用药9周，脑内可溶性Aβ升52%，提示可抑制Aβ聚集，且可溶性Aβ水平与认知障碍相关，早于斑块沉积，阻其积累关键。图7.金属螯合剂的结构抗Aβ免疫疗法通过主动或被动免疫促Aβ清除，机制有小胶质细胞吞噬、外周清除、解聚，但临床进展不顺：早期药AN1792引发脑膜脑炎等；甘特珠单抗减缓淀粉样蛋白沉积但疗效未证实；索拉珠单抗耐受好，却对1000名轻至中度患者无效；贝叶斯分析显示该疗法对AD无显著疗效。图8.主动免疫和被动免疫的分子基础调控分泌酶 Aβ由APP经β、γ分泌酶切割生成，α分泌酶切割可避Aβ产生，调控这三种酶是减少Aβ关键。 γ-分泌酶抑制剂（GSIs）与调节剂（GSMs）：GSIs理论减Aβ，但因影响Notch受体等，非选择性GSIs副作用大，如塞米司他试验终止；GSMs可选择性减Aβ₄₂，如NSAIDs证实可行性，他仑氟比尔II期安全但III期无效，且GSMs面临脑穿透性差等挑战。 β-分泌酶（BACE1）抑制剂：BACE1是APP切割限速酶，基因敲除小鼠无Aβ且无副作用，是理想靶点，但多种抑制剂如PF-05297909、AZD3293等因疗效欠佳或副作用终止试验，研发需克服选择性等难题。 α-分泌酶激活剂：α-分泌酶（主要ADAM10）切割APP可避Aβ产生，sAPPα有神经保护作用，AD患者脑脊液sAPPα低，激活策略有激活PKC、M1受体激动剂，激活ADAM10更优。图9.APP在非淀粉样变和淀粉样变通路中被α或β分泌酶裂解图10.人γ分泌酶复合物三维结构（PDBID：6IYC) 图11.已扩展临床试验的γ分泌酶抑制剂的结构图12.γ分泌酶调节剂的结构，这已经扩展了临床试验图13.人类BACE1的三维结构（PDBID：1FKN）图14.β分泌酶抑制剂的结构新兴靶点：tau蛋白与神经炎症通路 tau蛋白异常和神经炎症也是AD关键病理，相关靶点研究提供新方向。 tau靶向治疗 AD中tau过度磷酸化，解离聚集形成缠结致神经元损伤，治疗包括：激酶抑制剂：tau过度磷酸化与激酶（GSK-3β、CDK5）和磷酸酶失衡有关。GSK-3β抑制剂NP-031112临床前减tau磷酸化等，锂盐动物有效但患者无效，SB216763等因毒性或疗效差失败；CDK5抑制剂临床前能穿透血脑屏障降Aβ，但试验因疗效差或副作用终止。 tau聚集抑制剂：TRx0237 II期显高生物利用度，III期进行中；微管稳定剂如紫杉醇毒性大，TPI287对认知等有积极影响，烟酰胺小鼠实验有效，II期试验进行中。图15.tau聚集抑制剂（TRx0237）和tau稳定剂（紫杉醇和依泊替隆D）的结构图16.分别是抗甲状腺药物和不可逆葛兰素史克抑制剂的结构图17.GSK3抑制剂的结构，已延长临床试验 TREM2 TREM2是免疫球蛋白超家族跨膜受体，主要在髓系细胞表达，调控细胞功能。其基因变异与AD风险相关，p.Arg47His变异在欧美增风险2-3倍，东亚等人群无关联。TREM2缺陷减小胶质细胞聚集和吞噬，激活则促其极化等，发挥神经保护，但靶向治疗面临生物标志物缺乏等挑战。图18.TREM2信号通路 BIN1 BIN1是晚发型AD第二大遗传易感基因，通过tau通路影响AD风险，参与膜运输等，影响缠结形成。AD患者脑内BIN1表达异常，敲低可减tau介导神经毒性，还与自噬、钙通道运输相关，调控BIN1或能护神经。其他潜力靶点：神经递质、感染与Notum酶神经递质相关靶点 AD患者多神经递质紊乱，除已批准药物，还有：丁酰胆碱酯酶（BuChE）：AD患者脑内部分区域BuChE升高，抑制它或有神经保护作用，相关抑制剂在研。5-羟色胺受体（5-HT₆、5-HT₄）：5-HT₆拮抗剂英特匹定、5-HT₄拮抗剂普瑞昔单抗均进入II期试验。烟碱型乙酰胆碱受体（nAChR）：激动剂EVP-6124、POZANICLINE等在研，EVP-6124I/II期安全，III期评估认知改善。图19.胆碱酯酶抑制剂的结构，已扩展临床试验图20.胆碱酯酶抑制剂的结构感染相关靶点感染或参与AD发病，如牙龈卟啉单胞菌等感染增AD风险。COR388可抑牙龈卟啉单胞菌的牙龈蛋白酶，减神经炎症，小鼠实验挽救神经元、降Aβ₁₋₄₂，提供抗感染方向。 Notum酶 Notum负向调控Wnt信号通路，AD患者脑内Wnt信号下调，抑制Notum可护神经。Notum有明确晶体结构，是理想靶点，现有ABC99、褪黑素、咖啡因等抑制剂，ABC99增神经祖细胞，褪黑素减Aβ沉积和tau磷酸化，为研发更好抑制剂奠基。图21.（A）涉及Notum的羧酸酯酶活性在Wnt上释放棕榈油酸基团的化学反应。（B）结合相互作用的二维表示图22.卡通中所示的Notum结构图23.与激素褪黑激素相关的Notum抑制剂图24.咖啡因和茶碱是Notum抑制剂图25.恶二唑2和三唑3是由片段产生的两个互补先导 AD治疗需多靶点、多策略联合 AD病理复杂，单一靶点药难控病情，从经典到新兴靶点，研究者持续探索。虽部分研发遇挑战，但随病理理解加深及多靶点药物、联合治疗推进，未来有望研发出延缓甚至阻止AD进展的新药，为患者带来希望。关注 “CNSight” 公众号，后台回复“ AD靶点”即可获取原文资料 CNSight 一个专注于CNS前沿领域的资讯分享平台

临床3期免疫疗法临床结果

2024-06-12

·CPHI制药在线

礼来AD新药全票通过背后，Aβ假说遭质疑

关注并星标CPHI制药在线 6月10日，FDA外周和中枢神经系统药物咨询委员会（PCNS）就礼来的Donanemab用于治疗早期症状性阿尔茨海默病（AD）的生物制品许可申请（BLA）召开的会议结果出炉。委员会以11:0的票数一致赞同Donanemab的有效性，且一致认为其获益大于风险，并认可试验数据显示的Donanemab对早期记忆丧失的患者有效。穿过荆棘，Donanemab迎来胜利曙光 Donanemab是礼来研发的一款新一代Aβ单抗，可与β淀粉样蛋白亚型N3pG结合，从而促进患者大脑中淀粉样蛋白斑块的清除。此次PCNS的讨论，主要基于礼来 III 期TRAILBLAZER-ALZ 2研究的结论。这是一项随机、双盲、安慰剂对照III期临床研究，旨在评估Donanemab在早期症状性AD患者中的有效性和安全性。结果显示，在主要分析人群（低/中tau蛋白水平，n=1182，tau蛋白即AD进展的生物标志物）中，Donanemab组患者的iADRS评分(评估患者的认知能力和生活自理能力)和CDR-SB评分（临床痴呆评定量表，评估患者的认知能力）的下降速度分别减缓了35%和36%；并且近一半受试者（47%）在1年内没有疾病进展（定义为CDR-SB评分没有下降），而安慰剂组这一比例为29%。在总体人群（n=1736）中，与安慰剂组相比，Donanemab组患者的iADRS评分和CDR-SB评分的下降速度分别减缓了22%和29%。安全性方面，Ddonanemab组有24%患者出现淀粉样蛋白相关影像学异常-水肿（ARIA-E），6%患者出现有症状的ARIA-E；Donanemab组有31.4%患者出现脑微出血和浅表铁质沉积（ARIA-H），安慰剂组为13.6%。值得一提的是，无论ARIA-E和ARIA-H有无临床症状，均有致命风险。因此，对于ARIA高危人群，比如具有APOE4遗传标记的人，礼来建议进行更密切的监测。但是对于一般的AD患者来说，委员会认为，donanemab治疗的益处大于风险。一致性的投票结果，增加了donanemab获批上市的可能性。FDA通常在咨询委员会召开后1-2个月做出监管决定，如果获得批准，donanemab将成为美国市场上第二种治疗AD的药物（第一种为渤健/卫材的Leqembi）。值得一提的是，donanemab一路走来十分坎坷。2021年10月，礼来曾基于II 期临床试验 TRAILBLAZER-ALZ的结果，向FDA递交donanemab用于早期阿尔茨海默病加速批准的上市申请，该试验评估了donanemab 在早期症状性AD患者中的安全性、耐受性和有效性。不过2023 年 1 月，FDA 以患者数量不足的原因，发出了CRL。FDA称提交临床试验中提供的至少 12 个月药物暴露数据的患者数量有限，要求礼来公司提供至少100名接受了至少 12 个月的持续donanemab治疗的患者的数据。在礼来完成了III 期临床试验 TRAILBLAZER-ALZ 2后，于2023年5月再次递交上市申请，FDA原计划在今年第一季度对该上市申请做出决定，然而由于需要深入讨论 donanemab的几个核心问题，FDA决定召开专门委员会会议。此次一致性投票结果，是donanemab取得的又一大重磅进展，意味着donanemab 在将来的上市审批或许会有较好的前景，FDA 将于今年晚些时候做出决定。 Donanemab柳暗花明背后，Aβ蛋白假说遭质疑 AD作为一种难治的中枢神经系统疾病，已是目前照护成本最高昂、负担最重的疾病之一。由于AD致病机理复杂，多年来，这一领域药物研发折戟者众多。如辉瑞的Bapineuzumab、Mitsubishi Tanabe Pharma的Encenicline、TauRx的TRx0237、默沙东的Verubecestat等产品均折戟于此。直到2021年，渤健的Aducanumab被FDA加速批准上市，但后因有效性及安全性相关问题商业化失败。2023年1月，渤健/卫材的Lecanemab（仑卡奈单抗，商品名：Leqembi）获FDA加速批准上市，打破了AD领域长达十几年的沉寂。未来，若Donanemab顺利获得批准，其将与Lecanemab形成直接的市场竞争态势。值得一提的是，两款产品均属于Aβ（β-淀粉样蛋白）假说流派，这是目前AD领域的主流理论，其认为AD的形成过程为：淀粉样前体蛋白（APP）经酶异常切割形成Aβ，Aβ过量产生或清除不足，则聚集形成寡聚体，寡聚体进一步发展为原纤维，最终形成淀粉样斑块，该斑块具有一定毒性，影响神经细胞正常功能，最终致使AD形成。 Aβ假说虽是AD领域的主流理论，但也一直遭受质疑。就在6月5日，Science 发布重磅新闻：阿尔兹海默病发病机制领域的奠基性研究涉嫌图像造假。这一调查经历两年后，论文通讯作者终于承认论文图像涉嫌造假，并同意撤稿，目前该研究已被引用近 2500 次，是目前撤稿前被引用最高的论文，可以说这篇奠基性论文将大部分AD的研究引向这一方向。具体来说，论文中介绍了一种可以溶解在体液中的 Aβ 亚型：Aβ*56，与其他寡聚物相比，Aβ*56的分子量相对较大。研究人员分离了Aβ*56并将其注射到健康小鼠体内，之后，健康小鼠回忆简单、以前学过的信息的能力急剧下降。这一发现让科学界沸腾不已，这是首次将Aβ蛋白中的某项物质直接与AD联系起来。然而不少业界大咖在尝试在人体中寻找Aβ*56时，大都失败了。反复的失败，让科学家开始质疑这篇论文的真实性。2022年7月，science杂志发表了一篇调查报告，直指该研究涉嫌造假。报告提及，研究者在论文中发现了明显被修改或重复的图像。然而直到今年，该研究通讯作者才承认论文图片造假事实。多年来，它究竟影响了多少人相信和投入 β 淀粉样蛋白斑块研究，不得而知。不过也有人指出，Aβ*56只是Aβ蛋白中的一种，不能因Aβ*56研究造假而全盘否定Aβ假说。而且两款Aβ机制药物的临床试验成功起码部分地支持了Aβ假说。据世界卫生组织《2023年世界社会报告》数据显示，截至2018年全球约3310万人患有阿尔茨海默症，2050年这一数字将增至2.42亿。然而1998-2017 年，AD药物的研发成功率仅有2.7%。强劲的临床需求与"贫瘠"的获批药物形成强烈反差，因此不少药企在这一大蓝海赛道前赴后继。聚焦国内，先声药业、恒瑞医药、喜鹊医药、康缘药业等均有布局，未来谁将研发出开创性的药物，阿尔茨海默病市场在等一个答案。参考来源： 1.https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-public-participation-information-june-10-2024-meeting-peripheral-and-central-nervous-system#event-materials. 2.AAIC 2023 - Acumen's new amyloid approach impresses，Evaluate Vantage AAIC 2023 News Highlights，AAIC. 【企业推荐】【智药研习社直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床3期临床2期临床结果上市批准临床成功

2015-09-15

·BioSpace

FORUM Pharma Halts Clinical Trials for Alzheimer’s and Schizophrenia Drug

September 15, 2015 By Mark Terry , BioSpace.com Breaking News Staff The U.S. Food and Drug Administration (FDA) advised Waltham, Mass.-based FORUM Pharmaceuticals to halt its clinical trials of encenicline for Alzheimer’s disease yesterday. The FDA cited a small number of serious gastrointestinal (GI) side effects in the studies. As a result, FORUM halted the trial, discontinuing the medication and no new patients will be recruited until the clinical hold is lifted. The company is working with the FDA on a plan to continue the study. In addition, the FDA told the company that a trial in cognitive impairment in schizophrenia (CIS) has also been placed on a clinical hold. Two fully enrolled Phase III efficacy trials, however, that are evaluating encenicline to treat CIS will continue. In June 2015, FORUM received Fast Track designation for encenicline to treat CIS from the FDA . Encenicline is an oral, highly brain-penetrant, selective agonist of the alpha 7 receptor that is found in hippocampal and cortical neurons involved in cognition, in other words, brain cells involved in thinking. FORUM believes the drug activates alpha 7 receptors to increase its response to a naturally occurring neurotransmitter called acetylcholine. This, in turn, is believed to activate brain networks related to sensory gating, attention and cognition. A number of companies are working on Alzheimer’s medications, although it’s a difficult area with far more failures than successes. Swiss-based Roche reported in Dec. 2014 that it was discontinuing Scarlet RoAD, a Phase III study of gantenerumab on pre-dementia Alzheimer’s disease. In March 2015 Biogen, Inc. showed positive results of its Alzheimer’s drug, aducanumab. Another Roche drug, in an agreement with Germany-based Evotec , announced in July that its Phase IIb clinical trial of sembragiline in Alzheimer’s failed to meet its primary endoint. Eli Lilly and Company presented positive results for its Alzheimer’s drug, solanezumab, which had previously shown disappointing clinical trials in 2012. The company has shifted its focus to a subgroup of AD patients with a mild form of the disease that responded to the drug. A 2014 report in Alzheimer’s Research UK indicated that 244 Alzheimer’s drugs were tested between 2002 and 2012, and only one was approved, Lundbeck A/S ’s Ebixa. Even the few that are approved and on the market aren’t considered to be terribly effective. The biggest AD drug on the market is Eisai Company, Ltd. ’s Aracept. Others are Exelon, by Novartis , Razadyne by Janssen , and Namenda, by Actavis . Jeffrey Holford , an analyst with Jefferies and Co. , predicted that if the Lilly drug was approved, it could hit annual sales of more than $3 billion globally. In June 2015 Axovant Sciences Ltd. , which focuses on Alzheimer’s drugs, went public , raising $315 million overnight, the largest deal ever for a pre-revenue biotech company. The company’s product, RVT-101, which it bought from GlaxoSmithKline for $5 million and milestone payments, has shown some success in alleviating AD symptoms, but did not prevent the disease from progressing. Mark Schoenebaum , a biotech analyst who leads the biotech team at ISI Evercore , wrote an investor note in May that tries to pin down the size of the AD drug market. “There are 600,000 mild AD patients in the U.S.,” he wrote. “At a net price of around $20,000 (below TNFs), 65 percent penetration would yield a potential sales opportunity of around $8 billion in the U.S. alone. The ex-U.S. patient opportunity is similar, but price would probably be lower.”

临床3期临床2期并购快速通道临床结果

100 项与 Encenicline Hydrochloride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10702	Encenicline Hydrochloride	-	DB11726

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
阿尔茨海默症	临床3期	美国	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	阿根廷	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	澳大利亚	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	比利时	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	加拿大	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	捷克	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	法国	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	德国	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	意大利	FORUM Pharmaceuticals, Inc.	2013-10-01
阿尔茨海默症	临床3期	墨西哥	FORUM Pharmaceuticals, Inc.	2013-10-01

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临床结果

适应症

分期

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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


NCT01480232 (CTgov)	临床2期	尼古丁成瘾 \| 尼古丁依赖	345	NRT Patch (Placebo)+EVP-6124 (EVP-6124 + NRT Patch (Placebo))	觸構願衊廠衊襯鹽壓夢 = 網鹹鹽淵廠淵淵餘鹹選淵鬱醖遞鏇繭製夢網襯 (鬱觸築鑰壓窪衊繭齋蓋, 鏇壓齋鹽窪鏇淵獵顧膚 ~ 衊鏇壓壓廠衊齋遞衊鬱) 更多	-	2017-04-06
				NRT Patch (Placebo) (Placebo + NRT Patch (Placebo))	觸構願衊廠衊襯鹽壓夢 = 鹹積衊艱憲鬱繭積選糧淵鬱醖遞鏇繭製夢網襯 (鬱觸築鑰壓窪衊繭齋蓋, 壓鹽製淵鏇醖鬱糧齋構 ~ 鹽範蓋願夢衊醖網鬱醖) 更多
AAN2015	临床2期	阿尔茨海默症追加	409	Encenicline 0.27mg	憲窪鹹願遞廠獵觸淵顧(壓鹹蓋繭構選鹽艱廠網) = 鑰壓簾製製構鏇遞蓋齋衊憲顧淵齋範齋襯顧衊 (醖蓋築糧觸築鑰範廠願 )	积极	2015-04-06
				Encenicline 0.9mg	憲窪鹹願遞廠獵觸淵顧(壓鹹蓋繭構選鹽艱廠網) = 艱遞鑰廠製糧鏇夢鑰餘衊憲顧淵齋範齋襯顧衊 (醖蓋築糧觸築鑰範廠願 )
NCT01556763 (CTgov)	临床1期	中枢神经系统疾病 \| 分裂情感性障碍 \| 精神分裂症	21	Antipsychotic therapy (Placebo)	蓋顧鹽鏇選鹹繭蓋鑰膚 = 艱願憲齋夢鬱蓋鏇艱鬱餘鹹鏇憲餘夢鑰膚鹽餘 (觸遞範襯簾憲憲齋觸觸, 襯夢窪醖鹽鹹獵繭鹽獵 ~ 鹹獵鹽範觸簾艱選繭窪) 更多	-	2012-06-21
				Antipsychotic therapy+EVP-6124 (1.0 mg/day) (EVP-6124 (1.0 mg/Day))	蓋顧鹽鏇選鹹繭蓋鑰膚 = 鑰構憲蓋夢衊顧鏇繭廠餘鹹鏇憲餘夢鑰膚鹽餘 (觸遞範襯簾憲憲齋觸觸, 糧糧醖構選夢網遞窪範 ~ 膚鹽積簾窪鏇糧顧憲衊) 更多
NCT00766363 (CTgov)	临床1期	阿尔茨海默症	49	EVP-6124 (0.1 mg/day)+Rivastigmine+Donepezil (EVP-6124 (0.1 mg/Day))	範簾餘網艱範夢廠顧遞 = 鹹觸鏇壓鏇鹹憲鹽選築簾鏇鏇選醖衊夢顧糧糧 (繭壓鑰遞鏇蓋壓衊範鬱, 淵壓廠選廠鑰選選壓醖 ~ 蓋鹹壓齋繭衊網鑰積窪) 更多	-	2011-07-14
				EVP-6124 (0.3 mg/day)+Rivastigmine+Donepezil (EVP-6124 (0.3 mg/Day))	範簾餘網艱範夢廠顧遞 = 壓繭製窪繭獵願窪選獵簾鏇鏇選醖衊夢顧糧糧 (繭壓鑰遞鏇蓋壓衊範鬱, 獵襯膚製顧觸餘簾顧鑰 ~ 築壓構選築願餘鹹顧築) 更多