Allergan Plc

Dive Brief:Two House Democrats have called for an investigation of former Food and Drug Administration device director Jeff Shuren after The New York Times reported on potential conflicts of interest.Reps. Anna Eshoo, D-Calif., and Rosa DeLauro, D-Conn., sent a letter to the Office of Inspector General of the Department of Health and Human Services on Tuesday citing the article. The Times story covered how Jeff Shuren led the FDAs device center while his wife worked as legal counsel for medtech companies.At the very least, the article raises serious questions of appearance and serious conflict of interest, the representatives wrote in the letter, which was provided to MedTech Dive. The Times was the first to report on the investigation request Wednesday.Dive Insight:Jeff Shuren led the FDAs Center for Devices and Radiological Health for 15 years before stepping down in July.A month later, the Times reported that the former directors wife, Allison Shuren, represented medical device companies as co-chair of law firm Arnold & Porters life sciences and healthcare practice.Although Jeff Shuren signed ethics agreements, the article stated that their work sometimes intersected, such as when Arnold & Porter worked on an acquisition of Allergan as the FDA grappled with reports of a rare cancer associated with the companys breast implants.In response to the letter, an FDA spokesperson wrote Thursday that the FDA takes seriously its obligation to help ensure that decisions made, and actions taken, by the agency and its employees are consistent with ethics laws and regulations.The spokesperson added that the FDA does not comment on whether matters involving specific employees are the subject of internal or external reviews.Last month, the agency told MedTech Dive that it had no indication regulatory decisions were affected by Allison Shurens employment. However, an FDA spokesperson added that it appears there were certain instances from about 10 years ago for which Dr. Shuren should have either recused himself or sought ethics authorization to participate to avoid any potential appearance of bias.In their letter, Eshoo and DeLauro wrote that the only way to get to the truth is through an independent review to determine whether this is simply an appearance of impropriety or actual inappropriate and unethical conduct.A spokesperson for the Office of Inspector General said in an email to MedTech Dive, We received the letter and are reviewing it for appropriate action.Consumer advocacy group Public Citizen called for the OIG to open an investigation when the news broke in August. Public Citizen said the FDA should appoint a new director who has no conflicts of interest and will prioritize patients interests.Michelle Tarver was named acting director of the CDRH, and the FDA is searching for a permanent successor. Jeff Shuren is working with the agency as it transitions to a new leader.The FDA spokesperson told MedTech Dive last month that Jeff Shuren had been advised to exercise greater caution in matters concerning recusal, and is being provided additional administrative support to ensure future compliance. '

Serena Williams The FDA has faulted AbbVie’s promotion of the migraine drug Ubrelvy, calling the company out for an ad featuring Serena Williams that went out of bounds with claims about how quickly the product relieves symptoms.AbbVie received details of the FDA’s grievances in an untitled letter about the “When Migraine Strikes” TV spot it began running in support of Ubrelvy last year. The ad opens with tennis star Serena Williams in a talk show dressing room. Williams shows signs of suffering a migraine, putting her hand to her head and recoiling from a bright light.In voice-over, Williams says the options when a migraine strikes are “ride it out with the tradeoffs of treating” or “push through the pain and symptoms.” Ubrelvy, Williams tells us, provides another option. “One dose works fast to eliminate migraine pain,” the tennis legend says.The speed at which Ubrelvy acts is at the center of the FDA’s concerns with the ad. After saying Ubrelvy works fast, Williams is shown laughing and smiling and walking happily onto a brightly lit talk show stage. “This compelling before-and-after presentation in conjunction with claims such as, ‘One dose works fast to eliminate migraine pain’ and ‘UBRELVY QUICKLY ELIMINATES MIGRAINE PAIN’ misleadingly suggests that Ubrelvy eliminates migraine pain and symptoms more quickly than was demonstrated in the clinical trials,” the FDA said.The FDA notes the storyboard submitted for review said the opening scene in the dressing room takes place in the afternoon, and the shots of Williams “doing a final check in the mirror” before the talk show are in the evening. However, the administration said the finished ad “does not portray the passing of time in a manner that is consistent with the description in the storyboard.”That is a problem, because the Ubrelvy label outlines the drug’s effect on pain and other symptoms two hours after dosing. AbbVie included small text in the ad to clarify that “some people had pain freedom within 2 hours,” but the FDA found that caveat was “not sufficient to mitigate this misleading suggestion that Ubrelvy can eliminate migraine pain and symptoms more quickly than has been demonstrated.”The FDA also called AbbVie out for the statement “one dose works fast to eliminate migraine pain.” In the Ubrelvy clinical trials, about one-fifth of participants were free from pain two hours after taking one dose of the drug. Again, the FDA ruled that the clarifying text was insufficient to correct the misleading impression. The FDA raised specific concerns about making misleading statements in a celeb-led ad. “The use of a celebrity athlete in this TV ad amplifies the misleading representations and suggestions made and increases the potential for audiences to find the misleading promotional communication more believable due to the perceived credibility of the source,” the FDA said.AbbVie acquired Ubrelvy in its takeover of Allergan. The untitled letter states the FDA sent advisory comments to Allergan in 2020. The comments are redacted, but the FDA did publish its concerns that AbbVie “appears to be promoting Ubrelvy using similar claims and presentations in a misleading manner.”

Apimostinel CAS  : 1421866-48-9 机理：NMDA受体部分激动剂 状态：II期（IV）和I期（口服）临床试验 开发者：Allergan 也称为NRX-1074，是一种最初由Naurex开发的用于治疗抑郁症的药物-但目前正在由Naurex和Allergan（收购Naurex）共同研究。该药物对NMDA受体具有选择性的部分激动剂的功能，特别是在甘氨酸结合位点的变构位点。虽然Apimostinel表现出GLYX-13（另一种正在由Naurex开发的药物）相似的作用机制，但它与GLYX-13的不同之处在于其重量更显着。 一项比较分析表明，按重量计，Apimostinel的效力是GLYX-13的数千倍。之前我已经讨论了使用NRX-1074来治疗抑郁症的潜在好处，并提到它起效快，没有拟精神病作用并且似乎耐受良好。初步证据表明，服用Apimostinel后，抑郁症状可能在24小时内消失。 此外，Apimostinel的情绪增强作用似乎是剂量依赖性的，因此更高剂量的抗抑郁作用更为明显。值得一提的是，在早期试验中，单剂量的Apimostinel提供的缓解抑郁症状的症状要比SSRIs持续数周的缓解率更高。 BTRX-246040 CAS  : 1307245-86-8 机理: NOC 受体拮抗剂 状态: Phase II 开发者: BlackThorn Therapeutics 该药物最初由礼来公司进行研究，但现在似乎与黑刺李疗法联系在一起，并有了一个新的化学名称。2016年发表的一项概念验证研究报告称，LY-2940094(40毫克)是安全的，耐受性好，对治疗人类抑郁症有效——持续时间超过8周。 它作为一种抗抑郁药物的初步疗效通过格里-汉密尔顿抑郁评分量表(GRID-Hamilton Depression Rating scale)从基线到8周的17个总分的显著变化得到证明。此外，研究还发现LY-2940094在治疗的第一周内改变了对情绪刺激的处理——在情绪测试系列中，对积极面部表情相对于消极面部表情的认知增强就是证据。LY-2940094的初步调查数据是第一批显示NOP受体拮抗剂治疗抑郁症的潜力的数据。 关于BTRX-246040是否将继续用于治疗重度抑郁症，还是将其作为治疗其他神经系统疾病的治疗手段而接受调查，还存在一些争议。然而，与大多数抗抑郁药物相比，BTRX-246040表现出独特的作用机制。拮抗NOC受体似乎能增加大脑几个区域的单胺浓度，增强神经发生，并调节下丘脑-垂体-肾上腺轴的激活。 CERC-301 CAS  : 808732-98-1 机理: NMDA 受体 (NR2B-selective) 拮抗剂 状态: Phase II 开发者: Cerecor 2013年，FDA授予CERC-301“快速通道指定”，作为抑郁症和自杀意念的潜在辅助治疗药物。药效学研究表明，CERC-301对NMDA受体NR2B亚基具有高选择性拮抗作用。它对NMDA受体NR2B亚基的选择性亲和性被认为可以最大限度地降低与其他非选择性NMDA受体拮抗剂共同发生的拟精神分裂效应(如药物诱导的精神病)的可能性。 CERC-301的显影剂Cerecor表明，CERC-301具有快速的抗抑郁活性，从而在给药几分钟或几小时内就能缓解抑郁症状，而不是几天或几周。来自CERC-301试验的初步数据表明，该药物耐受性良好且安全。许多人认为，CERC-301是正在开发的治疗抑郁症的NMDA拮抗剂中最有前途的。 CERC-501 CAS  : 1174130-61-0 机理: KOR 拮抗剂 状态: Phase III 开发者: Janssen CERC-501是美国礼来公司首次研发的药物，名为LY-2456302。然而，在2015年2月，礼来公司将LY-2456302卖给了Cerecor公司，后者将其更名为CERC-501。2016年，CERC-501作为一种抗抑郁II期临床试验难治性抑郁症患者达到效果。 截至2017年8月，Cerecor将CERC-501出售给了Janssen Pharmaceuticals，后者正在继续开发其作为抑郁症的辅助疗法和药物滥用障碍的干预疗法。药效学评估显示，CERC-501是一种选择性的、短效的KOR (kappa阿片受体)拮抗剂。研究表明，激活kappa类阿片受体(KORs)会引发烦躁、幻觉和精神幻像效应——同时也会强化神经化学系统，与奖赏缺乏综合症、慢性压力和重度抑郁症有关。 用CERC-501拮抗kappa阿片受体(KOR)可能通过抵消已有的kappa阿片受体激活而促进抗抑郁效果。CERC-501与其他抗抑郁药(如SSRIs)联合使用可产生协同情绪增强作用(或比单独使用任何一种药物效果更好)。有报道称，在三期临床试验中，CERC-501的副作用不严重。 Liafensine (DB104) CAS:1198790-53-2 机理: SNDRI 状态: Phase II 开发者: Denovo Biopharma Liafensine (DB104)，原名BMS-820836，是一种SNDRI(5 -羟色胺-去甲肾上腺素-多巴胺再摄取抑制剂)或三层再摄取抑制剂，最初由AMRI开发，授权给百时美施贵宝治疗重度抑郁症。通过二期临床试验，该药物表现出与依西酞普兰(即依地普仑)和度洛西汀(即欣百达)相似的疗效。但百时美施贵宝终止其开发，主要原因是其疗效并不明显优于依地普乐和欣百达。 它的疗效相对于副作用和滥用潜力可能是Liafensine 被百时美施贵宝停止开发的原因。2017年，Denovo Biopharma获得了Liafensine的许可权，三重再摄取抑制剂的二期临床试验仍在继续。 JNJ-39393406 CAS : 953428-73-4 机理: Alpha-7 nAChR 调制器 状态: Phase II 开发者: Janssen JNJ-39393406用于治疗重度抑郁症和戒烟。与目前市场上大多数抗抑郁药相比，JNJ-39393406的独特之处在于，它仅作为-7烟碱乙酰胆碱受体的选择性正变构调制器(PAM)。药效学研究表明，该药物不会与-4-beta-2或-3-beta-4尼古丁乙酰胆碱受体或- 5-HT3受体相互作用。 更重要的是，药物似乎并没有与62种受体和酶相互作用。截至2018年2月，JNJ-39393406正在进行治疗重度抑郁症和尼古丁戒断的II期临床试验。JNJ-39393406以前被研究作为阿尔茨海默病和精神分裂症的干预措施，但是，经评估后被放弃了。 Ansofaxine (LY03005) CAS : 916918-84-8 机理: SNDRI 状态: Phase I 开发者: 绿叶制药 盐酸Ansofaxine(LY03005)是绿叶制药集团开发的用于治疗中重度抑郁症的三重摄取抑制剂(5 -羟色胺-去甲肾上腺素-多巴胺)。对Ansofaxine的药效学评价表明，它具有SNDRI的作用，是去文拉法辛的前药。然而，与去文拉法辛(即Pristiq)相比，Ansofaxine在同时调节血清素和去甲肾上腺素的同时，具有显著的多巴胺能效应。 到目前为止，Ansofaxine已经在两个人体试验中进行了评估，分别有72名和48名参与者。从现有的I期试验数据来看，Ansofaxine在40毫克至160毫克的剂量下似乎具有良好的耐受性和安全性。绿叶制药集团认为，与目前市面上的抗抑郁药相比，这种新药的副作用更少，起效更快。 MIN-117 CAS : 310392-93-9 机理: SDRI 状态: Phase II 开发者: Minerva Neurosciences MIN-117是一种血清素-多巴胺调制器，由Minerva神经科学公司开发用于治疗重度抑郁症。其作用机制针对受体和转运体的结合，包括:α- 1a受体;α-1B受体;5-HT2A受体;SERT(羟色胺转运体);和DAT(多巴胺转运体)。具体来说，MIN-117被证明是一种5-HT1A和5-HT2A拮抗剂;血清素和多巴胺再摄取抑制剂;α- 1a和α- 1b肾上腺素能受体调节剂。 Minerva神经科学提示MIN-117旨在解决重性抑郁症伴有共病焦虑或焦虑症状的患者的未控制症状。开发人员推测MIN-117将比目前市场上的大多数抗抑郁药物反应更快、更安全、耐受性更好。目前MIN-117作为干预抑郁症的临床试验正处于II期。 Seltorexant (MIN-202) CAS : 1293281-49-8 机理: Orexin-2 拮抗剂 状态: Phase II (complete) 开发者: Minerva Neurosciences & Janssen Seltorexant，又称MIN-202 (Minerva)和JNJ-42847922或JNJ-922 (Janssen)，是一种正在研究中的小分子、选择性orexin受体拮抗剂，由Minerva神经科学和Janssen开发。临床试验正在评估Seltorexant对重度抑郁症和失眠的治疗效果。据开发人员介绍，Seltorexant可以阻断大脑中促进觉醒的神经元的激活，特别是通过与orexin 2 (Orx-2)受体结合。 NSI-189 CAS  : 1270138-40-3  机理: 神经发生诱导物 状态: Phase III (?) 开发者: Neuralstem Inc. NSI-189是由Neuralstem公司开发的一种实验性药物，用于治疗重度抑郁症、认知障碍和神经退行性疾病。NSI-189是通过超过10000个化合物筛选，以确定哪些在体外(细胞)诱导最大程度的神经发生。NSI-189在体外和啮齿类动物中都表现出了疗效，随后将在患有重度抑郁症的人身上进行测试。 在II期临床试验中，NSI-189通过降低220名重性抑郁症患者的MADRS评分而未能达到其主要终点。NSI-189仍将继续接受神经系统和中枢神经系统疾病的治疗评估，包括:神经病、缺血性中风和认知障碍。 Rapastinel (GLYX-13) CAS  : 117928-94-6 机理: NMDA 受体调制器 状态: Phase III 开发者: Allergan Rapastinel(原名GLYX-13)是Allergan公司开发的一种药物(在收购Allergan之前由Naurex公司进行测试)，作为治疗耐药性抑郁症(或对2种或2种以上一线干预无效的抑郁症)的辅助干预手段。这种药物在口服时是不活跃的，而在静脉注射时是特别设计的。它在NMDA受体复合物的甘氨酸亚基的变构位点起选择性、适度的局部激动剂(混合拮抗剂/激动剂)的作用。 初步证据表明Rapastinel作用快速，并产生长期的抗抑郁反应。此外，Rapastinel似乎是通过抑制和增强NMDA受体介导的信号转导而增强认知功能的。无论动物年龄多大，给动物服用Rapastinel能增强记忆和学习能力，还能促进神经保护作用。 Rapastinel被归类为一种glyxin化合物，来源于修改单克隆抗体的结构，调节NMDA受体，称为“B6B21”。基于初步的试验数据，Rapastinel是治疗难治性抑郁症最有希望的治疗手段之一。 SAGE-217 CAS  : 1632051-40-1 机理: GABAA受体调制器 状态: Phase III 开发者: Sage Therapeutics Sage -217是由Sage Therapeutics公司研发的一种研究性化学药物，用于治疗重度抑郁症和产后抑郁症，以及帕金森病、失眠和癫痫的原发性震颤。据Sage Therapeutics公司介绍，Sage -217是一种合成的孕烷神经类固醇，它是GABAA受体的一种正变构调制器。SAGE-217的目标是改进并继承Brexanolone ——另一种圣人治疗抑郁症的药物，目前已进入临床试验阶段。在用于治疗女性产后抑郁症(PPD)患者的3期试验ROBIN中，达到了试验的主要和次要终点。重症抑郁三期失败。 Travivo (Gepirone ER) CAS:83928-66-9;83928-76-1 机理: 5-HT1A 选择性部分激动剂 状态: 等待 FDA 批准 开发者: Fabre-Kramer Pharmaceuticals Travivo (Gepirone ER)是一种抗抑郁药物，最初因疗效问题被FDA多次拒绝。它第一次被否决是在2004年，然后在2007年再次被否决。FDA在2015年审查了Gepirone的数据，推翻了他们最初对该药物的排斥——给予了有利的评价。2016年3月FDA对Travivo (Gepirone ER)治疗重度抑郁症的疗效进行了有利的规定。 参考原文：30+ New Antidepressants (2018): Drugs In Clinical Trials TIS2024第四届自免疾病细胞疗法与干细胞疗法论坛重磅来袭，点击图片查看重磅嘉宾，合作详询：王晨 180 1628 8769 （扫码立即报名获取TIS2024免费票）