The New York State Psychiatric Institute

本届大会以“共建创新生态 共赢产业未来”为主题，聚焦生物医药出海与国际化创新、创新药投融资、医疗器械等产业发展风向标，打造“高端化、国际化、专业化、立体化”的年度盛会。 去年11月，总部位于波士顿的生物技术公司Karuna Therapeutics，向FDA提交了一种名为KarXT的精神分裂症新药上市申请。9月26日，KarXT将迎来最终审批结论。 如果FDA给KarXT开了绿灯，这种药物将成为几十年来第一种不依赖直接阻断多巴胺受体的精神分裂症新疗法。而KarXT的监管成功，也可能为更多新的精神病药物铺平道路。 但是，在这个药物发现十分困难的领域，行业仍然存在挑战。 1 难啃的硬骨头 2022年，WHO推测全球约有2400万人患有精神分裂症。NIH研究表明，美国精神分裂症和相关精神障碍的患病率在0.25%至0.64%之间。精神分裂症是所有精神疾病中死亡率最高的疾病之一，据估计，精神分裂症患者的寿命可能比其他人群短15至20年。 令人无奈，科学家们尚不知道是什么导致了这种疾病。事实上，精神分裂症最好被理解为一种综合症，或一系列症状。 哥伦比亚大学和纽约州立精神病研究所的精神病学家Joshua Kantrowitz，将精神分裂症比作咳嗽，这是一个人的上呼吸道出现问题的外在表现。咳嗽可能有几种原因，如过敏、哮喘、流感或其他病毒，但咳嗽是这些原因中任何一种的可感知症状。 Kantrowitz说：“精神分裂症有点像那样，但更复杂一点，因为我们处理的是大脑而不是肺。” 精神分裂症患者会经历三大类症状：与患者病情相关的阳性症状，代表功能缺陷的阴性症状和认知障碍。阳性症状是最常见的，包括幻觉和幻听；阴性症状通常是抑郁症样的，如社交退缩和无法感受快乐。许多精神分裂症患者也表现出认知障碍。 对于一些精神分裂症患者来说，抗精神病药物有助于减轻症状。但现有疗法并不是对每个人都有效。大约三分之一的精神分裂症患者表现出所谓的难治性精神分裂症，即使药物确实缓解了精神分裂症的症状，它们的副作用也会使人衰弱。 所有可用于精神分裂症的抗精神病药物都能拮抗神经元D2多巴胺受体。但D2受体拮抗剂的一个问题是，多巴胺需要在大脑的多个部分，而不仅仅是与精神病有关的部分。抑制大脑中多巴胺的含量会导致副作用，如震颤或僵硬、体重增加和高泌乳素血症。 “正如你所想象的，这可能会对人们的自我认同以及服用这些药物的愿望产生重大影响。”马萨诸塞州布里格姆姆克林医院精神分裂症和双相情感障碍研究项目主任Ann Shinn说。 如果人们因为药物的副作用而不能或不愿服用药物，那么药物就无法帮助治疗精神病，而精神分裂症患者也没有其他药物可以求助。 “在过去的20年里，该领域一直在推出类似的、略有不同的D2拮抗剂，但这些药物并没有起到任何作用。”Kantrowitz说。 2 新的希望浮现 20世纪90年代，礼来在测试一种新的分子，xanomeline，作为阿尔茨海默病的可能治疗方法。在这种分子的试验中，研究人员观察到，它减轻了有时可能源于阿尔茨海默病的精神病。 礼来进行了一项小型试验，以评估xanomeline治疗精神病的潜力。该公司认为，这种分子会引起太多的胃肠道副作用，因此将其搁置。 但当时在生物技术公司PureTech Health担任副总裁的Andrew Miller，看到了这种分子（一种毒蕈碱激动剂）作为一流疗法的潜力。因此，2012年，Miller从礼来获得了xanomeline的许可，并成立了Karuna来开发它。 “业界被锁定在同一类药物上，对它们进行研究、渐进式创新，但要引入一些根本不同的东西确实很有挑战性。”Miller说，“所以，正如我和其他人在xanomeline上看到的，这可能代表着一个新的类别。” 但副作用的挑战仍然存在。 Miller和Karuna团队发现的解决方案是添加trospium，一种毒蕈碱拮抗剂，以对抗全身性胃肠道副作用。关键是，trospium不能穿过血脑屏障，“它使我们能够改善或阻断胃肠道等外周组织中毒蕈碱受体的激活，副作用就是在胃肠道中产生的，但不会改变基于中枢脑的治疗益处”。 毒蕈碱机制 在Karuna的尝试下，trospium和xanomeline组合成为KarXT。 虽然xanomeline可能是第一个被批准的这类新的抗精神病药物，但它不是唯一的一种。 Emraclidine，一种来自生物技术公司Cerevel Therapeutics的精神分裂症靶向分子，也作用于毒蕈碱受体。差异在于，xanomeline同时作用于M1和M4受体，而emraclidine只作用于M4受体，这在理论上不需要另一种分子（如trospium）来抑制副作用。 其他致力于研究治疗精神分裂症的毒蕈碱激动剂的公司，包括Sosei Heptares和Anavex Life Sciences。 这些分子提供了一个引人注目的新选择。“我们有可能拥有这一类新药，它们对症状确实有帮助，而且不会产生患者无法忍受的不良反应，这确实令人兴奋。”Shinn说。 研究人员尚未将KarXT与传统的D2拮抗剂进行直接比较，以确定哪种药物在控制精神病方面更胜一筹。Miller说，迄今为止，减少阳性和阴性症状一直是研究的重点，Karuna也是根据这一优势向FDA提交数据的。他还补充，这种疗法在减少认知障碍方面也有希望。 虽然毒蕈碱激动剂的确切作用机制尚未确定，但研究人员认为，它们仍然会影响大脑中多巴胺信号的数量，只是通过间接的方法。 Karuna团队推测假设，在大脑中，xanomeline作用于前额叶皮层中的γ-氨基丁酸能中间神经元上的M1受体。通过一系列步骤，这种活动减少了多巴胺的产生。但M1、M4以及类似的受体M2和M3，也存在于整个外周神经系统和胃肠道系统中，这可能就是为什么xanomeline本身会引起胃肠道副作用，如恶心，呕吐和腹泻。 Emraclidine对M4受体的作用，类似于xanomeline作用于M1受体，它最终会导致释放的多巴胺分子数量减少。但它是通过激活使用乙酰胆碱生成神经元的途径来实现这一目的的。 由于不直接抑制D2受体，xanomeline和emraclidine避免了D2拮抗剂所带来的与运动相关的副作用。 3 黄金时代之前 去年12月，BMS和艾伯维分别以数十亿美元的价格收购了Karuna和Cerevel。 投资公司Stifel的分析师在当时的一份报告中称，这些交易“证实了精神病学的新机制具有巨大的潜力”。行业观察人士认为，这些交易可能表明，大型制药公司在2010年代因试验失败而退出后，准备再次尝试精神病学。 但现在就宣布精神病药物的新黄金时代，还为时过早。 麻省理工学院和哈佛大学布罗德研究所斯坦利精神病学研究中心主任Steve Hyman说，精神病药物的发现极其困难，许多障碍阻碍了开发新的大脑疗法。不仅大脑是人体中最复杂的器官，这使得药物发现变得困难，而且，神经学研究人员不能像癌症研究人员那样，采取脑组织样本进行实验。 研究人员面临着精神疾病的动物模型缺乏的问题，目前还没有精神分裂症的动物模型。 此外，该领域无法获得精神分裂症等疾病的生物标志物，所以试验必须在被诊断患有精神分裂症的异质人群中进行。 “这意味着，在临床试验中检测信号的能力非常微弱，”Hyman说。他的结论是，“复制Karuna和Cerevel的成功可能并不容易”。 但Miller乐观地认为，通过利用礼来研究人员首次发现的结果，该领域在开发新药方面正变得越来越好。 “精神病学创新的一个重要来源，就是这些意想不到的效果，”他说。“这就是抗抑郁药被发现的原因。抗精神病药物就是这样被发现的。抗焦虑药也是这样被发现的。因此，有创新和洞察力的来源。我认为我们在转化这些方面做得更好。“ Miller希望，KarXT能很快获得FDA的批准。而Karuna也将KarXT推入它最初被发现的地方：该公司正在测试KarXT在治疗阿尔茨海默病患者精神病方面的有效性，并且可能开始测试该治疗对阿尔茨海默病相关认知障碍的有效性。 参考文献： New schizophrenia medications could signal a comeback for psychiatric drugs 同写意媒体矩阵，欢迎关注↓↓↓

TUESDAY, Sept. 24, 2024 -- Psilocybin could help people suffering from a mental health problem that can lead to eating disorders , a new study suggests. Psilocybin, the active chemical in “magic” mushrooms, significantly reduced symptoms in people with body dysmorphic disorder (BDD), researchers reported Sept. 24 in the journal Psychedelics . BDD causes an obsessive preoccupation with perceived flaws in one’s physical appearance, and is frequently tied to eating disorders and other unhealthy behaviors, researchers said. For this pilot trial, eight people with hard-to-treat BDD received a single 25-milligram dose of psilocybin. Brain scans showed that the psilocybin treatment increased levels in connectivity between different brain regions related to emotional processing, cognitive activity and feelings and thoughts about oneself. People who had the greatest strengthening in these connections experienced the most improvement in their BDD symptoms within a week, results show. The findings “align with a growing body of evidence indicating that psychedelic compounds like psilocybin can promote mental health by enhancing the brain's capacity for flexibility and integration,” concluded the research team led by Chen Zhang , a research assistant with the New York State Psychiatric Institute. “By facilitating communication within and between brain networks that are often dysregulated in psychiatric disorders, psilocybin may help restore more adaptive cognitive and emotional functioning,” the research team said in a journal news release. However, more studies in larger groups of people with BDD are needed to verify the effectiveness of the treatment and how long it will last, the researchers noted. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

CUPERTINO, Calif., Aug. 27, 2024 (GLOBE NEWSWIRE) -- Reviva Pharmaceuticals Holdings, Inc. (NASDAQ: RVPH) (“Reviva” or the “Company”), a late-stage pharmaceutical company developing therapies that seek to address unmet medical needs in the areas of central nervous system (CNS), inflammatory and cardiometabolic diseases, today announced it will host a virtual key opinion leader (KOL) event on Wednesday, September 4, 2024 at 2:00 PM ET. To register for the event, click here. The event will feature Brian Kirkpatrick, MD (Professor, Psychiatric Research Institute, University of Arkansas for Medical Sciences, Arkansas) and Mark Opler, PhD, MPH (Chief Research Officer at WCG Inc., Executive Director of the PANSS Institute, New York), who will discuss the unmet medical need and current treatment landscape for patients suffering from symptoms of schizophrenia, and application of speech latency as an objective vocal biomarker in schizophrenia clinical trials for evaluation of negative symptoms. The discussion will focus on reviewing results of the vocal biomarker data and their relationship to the primary efficacy endpoint and key efficacy secondary endpoints negative symptoms, social functioning, social cognition and CGI from brilaroxazine Phase 3 RECOVER-1 trial in schizophrenia. A live question and answer session will follow the formal presentations. About Brian Kirkpatrick, MD, MSPHBrian Kirkpatrick, MD, MSPH, Professor in the University of Arkansas for Medical Sciences (UAMS) Department of Psychiatry, is a nationally and internationally renowned expert on schizophrenia and related disorders, whose pioneering research has advanced many life-changing treatments. Dr. Kirkpatrick graduated from the University of Texas Medical School at Houston and completed his residency in psychiatry at the University of North Carolina at Chapel Hill (UNC). After residency, he participated in the UNC Robert Wood Johnson Clinical Scholars Program, receiving a Master of Science in Public Health with a concentration in epidemiology. He also completed a fellowship in neuropharmacology at UNC. Dr. Kirkpatrick joined the Maryland Psychiatric Research Center at the University of Maryland School of Medicine in Catonsville and later served as vice chair of psychiatry at the Medical College of Georgia. He subsequently served as chair of the Department of Psychiatry at Scott & White Hospital and the Texas A&M School of Medicine, and the Department of Psychiatry and Behavioral Sciences at the University of Nevada, Reno School of Medicine. He joined the UAMS Department of Psychiatry in 2022. Throughout his career, Dr. Kirkpatrick has focused on schizophrenia and related disorders. He co-chaired the Consensus Development Conference on Negative Symptoms sponsored by the National Institute of Mental Health (NIMH). He has received competitive funding from NIMH, the National Institute of Diabetes and Digestive and Kidney Diseases, the Brain and Behavior Research Foundation, and the Scottish Rite Foundation. He served as an associate editor of Clinical Schizophrenia and Related Psychoses and is on the editorial board of Schizophrenia Bulletin. About Mark Opler, PhD, MPHMark Opler, PhD, MPH holds the titles of Chief Research Officer at WCG Inc. and Executive Director of the PANSS Institute. Dr. Opler has served as a faculty member in the Departments of Psychiatry and Environmental Medicine at New York University School of Medicine and in the Department of Neuroscience at Columbia University, College of Physicians and Surgeons. His academic research focuses on the etiology, phenomenology, and treatment of serious and persistent mental disorders. He is a co-author and developer of several clinical assessment tools, including the SNAPSI, CGI-DS, and NY-AACENT. He is a contributor to the latest edition of the PANSS Manual©. Dr. Opler has received research support from the US NIMH, the Brain & Behavior Foundation (formerly NARSAD), the Stanley Medical Research Institute, and the Qatar National Research Fund. He has co-authored more than 50 peer-reviewed publications and has contributed to multiple book chapters and review articles on clinical assessment, research methodology, and mental health. He received his PhD and MPH from Columbia University and his BSc from SUNY at Stony Brook. He is a graduate of the Psychiatric Epidemiology Training Program at Columbia University and completed his postdoctoral fellowship at the New York State Psychiatric Institute. About BrilaroxazineBrilaroxazine is an in-house discovered new chemical entity with potent affinity and selectivity against key serotonin and dopamine receptors implicated in the pathobiology of several conditions including schizophrenia, psoriasis and interstitial lung diseases like pulmonary hypertension, pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). Positive topline data from the global Phase 3 RECOVER-1 trial in schizophrenia demonstrated the trial successfully met all primary and secondary endpoints with statistically significant and clinically meaningful reductions across all major symptom domains including reduction in key proinflammatory cytokines implicated in the pathobiology of schizophrenia and comorbid inflammatory conditions at week 4 with 50 mg of brilaroxazine vs. placebo with a generally well-tolerated side effect profile comparable to placebo and discontinuation rates lower than placebo. Positive data from a clinical drug-drug interaction (DDI) study investigating the potential effect of CYP3A4 enzyme on brilaroxazine in healthy subjects supports no clinically significant interaction when combined with a CYP3A4 inhibitor. Reviva believes that a full battery of regulatory compliant toxicology and safety pharmacology studies has been completed for brilaroxazine. Reviva intends to develop brilaroxazine for other neuropsychiatric indications including bipolar disorder, major depressive disorder (MDD) and attention-deficit/hyperactivity disorder (ADHD). Additionally, brilaroxazine has shown promising nonclinical activity for inflammatory diseases psoriasis, pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) with mitigation of fibrosis and inflammation in translational animal models. Brilaroxazine has already received Orphan Drug Designation by the U.S. FDA for the treatment of PAH and IPF conditions. To learn more about the clinical and preclinical data available for brilaroxazine, please visit revivapharma.com/publications. About RevivaReviva is a late-stage biopharmaceutical company that discovers, develops, and seeks to commercialize next-generation therapeutics for diseases representing unmet medical needs and burdens to society, patients, and their families. Reviva’s current pipeline focuses on the central nervous system (CNS), inflammatory and cardiometabolic diseases. Reviva’s pipeline currently includes two drug candidates, brilaroxazine (RP5063) and RP1208. Both are new chemical entities discovered in-house. Reviva has been granted composition of matter patents for both brilaroxazine and RP1208 in the United States, Europe, and several other countries. Forward-Looking StatementsThis press release contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act, as amended, including those relating to the Company’s 1-year open label extension (OLE) trial evaluating the long-term safety and tolerability for brilaroxazine in schizophrenia, the registrational Phase 3 RECOVER-2 trial, the Company’s expectations regarding the anticipated clinical profile of its product candidates, including statements regarding anticipated efficacy or safety profile, and those relating to the Company’s expectations, intentions or beliefs regarding matters including product development and clinical trial plans, clinical and regulatory timelines and expenses, planned or intended additional trials or studies and the timing thereof, planned or intended regulatory submissions and the timing thereof, trial results, market opportunity, ability to raise sufficient funding, competitive position, possible or assumed future results of operations, business strategies, potential opportunities for development including partnerships, growth or expansion opportunities and other statements that are predictive in nature. These forward-looking statements are based on current expectations, estimates, forecasts and projections about the industry and markets in which we operate and management’s current beliefs and assumptions. These statements may be identified by the use of forward-looking expressions, including, but not limited to, “expect,” “anticipate,” “intend,” “plan,” “believe,” “estimate,” “potential, “predict,” “project,” “should,” “would” and similar expressions and the negatives of those terms. These statements relate to future events or our financial performance and involve known and unknown risks, uncertainties, and other factors which may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Such factors include those set forth in the Company’s most recent Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and the Company’s other filings from time to time with the Securities and Exchange Commission. Prospective investors are cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date of this press release. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Corporate Contact:Reviva Pharmaceuticals Holdings, Inc.Laxminarayan Bhat, PhDwww.revivapharma.com Investor Relations Contact:LifeSci Advisors, LLCBruce Macklebmackle@lifesciadvisors.com Media Contact:Kristin Politikpoliti@lifescicomms.com(646) 876-4783