Diazepam

编者按：随着神经系统疾病在全球范围内负担的持续加重，人们对有效治疗复杂中枢神经系统（CNS）疾病的疗法需求日益迫切。作为世界领先的神经科学转化研究创新企业之一，罗氏（Roche）站在应对这一挑战的第一线——过去十年间，罗氏在为患者带来创新疗法方面取得了重大进展，其针对多发性硬化、脊髓性肌萎缩、视神经脊髓炎和杜氏肌营养不良的新药近期相继获批。2025年4月，罗氏宣布启动新一代阿尔茨海默病治疗药物trontinemab的3期临床试验项目，该药物运用了罗氏的“脑穿梭（brain shuttle）”技术平台，能更高效地穿越血脑屏障——这一直是神经系统药物研发领域的重大难题。在这篇文章中，我们与罗氏医药研究与早期开发（pRED）神经科学及罕见病领域全球负责人Azad Bonni博士进行了独家对话，探讨罗氏如何加速研发进程，以及为何我们有望迎来一个为严重中枢神经系统疾病患者带来实质性突破的新纪元。Azad Bonni博士现任医药研究与早期开发（pRED）神经科学及罕见病领域全球负责人，全面领导这些领域的研发战略与管线布局。在罗氏任职期间，他成功推动多项突破性疗法从实验室走向临床，包括阿尔茨海默病药物trontinemab、多发性硬化疗法Brain Shuttle-CD20、天使综合征治疗药物rugonersen等。此外，他还积极推动罗氏在神经科学领域的全球合作与并购、参与创立罗氏人类生物学研究所（原罗氏转化生物工程研究所）并担任其科学顾问。加入罗氏前，Azad Bonni博士曾任华盛顿大学圣路易斯分校医学院神经科学系主任，并领导McDonnell细胞和分子神经生物学中心。Azad Bonni博士兼具基础科研与产业领导的复合背景，在学术创新与药物研发转化领域具有深远影响力。感谢您接受我们的采访。作为神经科学领域的全球领导者之一，罗氏在推动复杂CNS疾病治疗方面，如何规划实现真正的突破性进展？Azad Bonni博士：神经科学治疗领域长期以来被视为医学界最具挑战的领域之一。但我认为，我们正站在这一领域重大突破的临界点上。如果从罗氏自身的经历来回顾神经科学疗法的发展史，便能很好地印证这一点。20世纪60年代，罗氏从Librium和Valium作为起点开始研发苯二氮䓬类药物；此后又历经十年，才推出帕金森病治疗药物Madopar；又过了二十年，才通过基因泰克公司（现属罗氏）推出急性卒中治疗药物tPA。在整个20世纪的大部分时间里，神经科学领域的新疗法类别寥寥无几——大约每十年甚至二十年才有一种。自2017年起，这个现象发生了显著转变。我们相继推出了治疗多发性硬化的Ocrevus、治疗脊髓性肌萎缩的Evrysdi、以及治疗视神经脊髓炎谱系障碍的Enspryng，现在又推出了治疗杜氏肌营养不良的Elevidys。在相对较短的时间内实现了四款重要疗法上市——这在此前的中枢神经治疗领域是前所未有的。这绝非偶然，它预示着我们已经迎来了一个真正的转折点。更令人振奋的是，我们正在阿尔茨海默病和帕金森病等重大常见疾病领域取得实质性进展——这些领域历来被视为难以攻克的医学高峰。在阿尔茨海默病领域，我们正推进采用创新脑穿梭技术的trontinemab，以及γ分泌酶调节剂nivegacetor的研发；在帕金森病领域，我们正在开发靶向聚集态α-突触核蛋白的prasinezumab——该靶点正是帕金森病的一个关键病理标志。这一突破性进展主要得益于三大驱动因素：首先，人类遗传学的进展为疾病机制研究提供了关键洞见；其次，我们对疾病生物学的认知取得了显著提高；再者，新型技术平台正加速药物发现与开发进程。这些进步共同奠定了坚实的基础，也正因如此，我们相信神经科学治疗领域正在迈入一个具有实质进展的新纪元。您提到了小分子药物和抗体疗法，在针对中枢神经系统疾病时，罗氏在选择治疗模式方面有什么考量？Azad Bonni博士：长期以来，小分子药物一直是神经科学领域的主要治疗手段，未来也必将持续发挥重要作用。这类药物具有多重优势，且近年来已在神经科学领域取得了显著进展。与此同时，生物制品等大分子药物的临床价值正日益凸显。其在神经科学领域应用的核心挑战始终在于血脑屏障——虽然这一屏障对保护大脑功能至关重要，却也使治疗药物难以到达脑组织。这正是我们开发"脑穿梭"等创新技术的意义所在。该技术平台能有效突破血脑屏障限制，将治疗药物直接输送到大脑，为神经系统疾病的治疗开辟全新的可能性。所以，简而言之——并不存在放之四海皆准的方案。我们需要运用多种治疗模式，充分利用不断扩展的治疗手段，才能应对神经系统疾病的复杂挑战。而这正是罗氏乃至整个行业正在践行的研发策略。许多药企都在转化研究的“死亡谷”中苦苦挣扎。罗氏采取了哪些差异化策略来更好地衔接早期药物发现与临床开发？Azad Bonni博士：得益于我刚才提到的那些科学突破，我们现在可以用一种全新的、更加现代的方式来开展神经科学领域的药物研发。这意味着，我们会将重点放在那些有确凿遗传证据、致病机制研究较为透彻、并能应用尖端技术平台的疾病上。换言之，我们优先选择生物学置信度较高的靶点和疾病领域。在神经科学领域，我们虽然仍处于这些发现转化为经临床验证靶点的早期阶段，但正在取得稳步进展。另一个关键因素是提高临床前模型的预测有效性——确保实验数据能更准确地反映在人类身上的实际效果。这是一项持续推进的工作。同样重要的是开发更好的生物标志物，可靠的标志物对研发全链条的决策至关重要。这三个要素——选择高置信度靶点、优化转化模型、开发优质生物标志物——正是跨越你所说的“死亡谷”的核心策略。许多企业曾深耕神经科学领域，但随后这一领域的研发热潮逐渐消退。然而近期，我们看到行业重焕活力与热情。在您看来，这次复兴与以往有何本质区别？我们又该如何避免重蹈覆辙？Azad Bonni博士：这是个很好的问题，我完全同意你的说法——神经科学确实正经历一场明显的复兴浪潮，我预计这股势头将在未来二十年持续加速。特别要强调的是生物标志物在其中的关键作用。以阿尔茨海默病为例，虽然针对β淀粉样蛋白的疗法研发历经25年并曾屡遭挫折，但这些经验进一步深化了我们对疾病的理解，并推动了生物标志物的发展。这些标志物彻底改变了药物的研发模式：它们让我们能在临床前研究和临床试验中提出更精准的科学问题，开展机制验证研究——从而在投入大量时间和资源进行后期研发之前，尽早确定药物是否起效。这种实验医学方法对阿尔茨海默病领域的近期进展功不可没，现在我们需要将这种思维扩展到帕金森病等其他疾病领域。尽管阿尔茨海默病研究仍有很长的路要走，但医药企业、生物科技公司和学术机构已通过生物标志物的开发建立起坚实的基础。这样的合作模式不仅可以，也应当推广到其他复杂的神经系统疾病中。除生物标志物外，您认为罗氏还在探索哪些有望在未来五年彻底改变药物发现和转化范式的技术？Azad Bonni博士：首先我想要重点介绍我们的"脑穿梭"技术平台。虽然当前有许多前沿技术正在研发中，但我相信这项技术有可能彻底革新脑部药物递送方式。如先前所述，血脑屏障会阻止抗体等大分子入脑——传统抗体通常只有约0.1%能进入大脑，且多富集于脑室周围，难以均匀分布至全脑组织。“脑穿梭”技术通过利用天然的胞吞转运机制（生物体跨屏障运输物质的自然途径）解决了这一难题。通过先进的蛋白质工程技术，我们开发出例如trontinemab这样的创新抗体分子——该药物靶向阿尔茨海默病的淀粉样蛋白斑块，其特殊结构域可与转铁蛋白受体结合，通过触发转胞吞转运作用主动穿越血脑屏障。值得注意的是，这种设计能确保抗体在外周循环和入脑后均能保持正常功能，避免在血管内皮细胞中异常蓄积。Trontinemab是我们目前利用该技术所开发进展最快的项目。在一项2a期临床试验中，它表现出了快速而强大的淀粉样蛋白斑块清除能力，远超传统抗体。更令人振奋的是，它引发的淀粉样蛋白相关影像学异常（ARIA）发生率更低——这是传统淀粉样蛋白疗法常见的不良反应，我们认为其安全性优势可能是由于其独特的入脑途径所致。但“脑穿梭”技术的潜力远不止于淀粉样蛋白和阿尔茨海默病。该平台可适配其他抗体、并拓展至多种神经系统疾病，甚至有望应用于抗体之外的其他治疗模式，为脑部疾病的治疗开辟全新的可能性。最后一个问题——如果您有机会在神经科学领域实现一个愿望，您最希望达成的目标是什么？Azad Bonni博士：这是一个很好的问题。我最近一直在思考“预防神经病学”这个领域。例如，在心脏病学领域，预防措施已相当成熟——降压药、他汀类药物、再到如今的GLP-1激动剂，这些干预手段都专注于在严重疾病发生之前解决风险因素。我相信神经病学领域也将迎来类似的转折点。以阿尔茨海默病为例：研究显示，60岁及以上人群中约40%的人已出现脑内淀粉样蛋白病理改变，尽管尚未表现症状。设想这样一个未来——精准诊断技术可以及早识别这些人，我们也有针对性的疗法来阻止其病情发展到有症状的地步。这正是我为之振奋的未来图景，而我相信，这样的未来正越来越接近现实。罗氏同时拥有制药和诊断两大业务板块，这使我们能推进精准预防策略，从根本上改变神经系统疾病的管理模式。当然，这并不意味着我们不再关注对已表现出症状患者的治疗——只要存在未被满足的医疗需求，这一方向仍然至关重要。但随着社会越来越重视保持健康和生活质量，二级预防——即在症状出现之前进行干预，必将成为未来医学越来越重要的一部分。能参与塑造这样的未来，着实令人振奋。Advancing the New Era of Neuroscience: A Conversation with Dr. Azad Bonni, SVP and Global Head of Neuroscience & Rare Diseases, Roche Pharma Research & Early DevelopmentEditor’s Note: As the global burden of neurological diseases continues to rise, the need for effective treatments for complex CNS (central nervous system) disorders has never been more urgent. At the forefront of addressing this challenge is Roche, one of the world’s leading innovators in neuroscience translational research. Over the past decade, Roche has made significant progress in bringing new therapies to patients, with recent approvals for conditions including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica, and Duchenne muscular dystrophy. In a major step forward, Roche announced in April 2025 the initiation of a Phase III program for trontinemab, a next-generation Alzheimer’s therapy that leverages the company’s brain shuttle platform to more effectively cross the blood-brain barrier—a long-standing hurdle in neurological drug development. With this momentum, we sat down for an exclusive conversation with Dr. Azad Bonni, SVP and Global Head of Neuroscience & Rare Diseases at Roche pRED, to discuss how Roche is accelerating research and development and why we may be entering a new era of meaningful breakthroughs for patients affected by devastating CNS diseases.Thank you for joining us, Dr. Bonni. As a global leader in neuroscience, how does Roche envision making meaningful progress in addressing complex CNS diseases?Azad Bonni: Neuroscience therapeutics has long been considered one of the most challenging areas in medicine—often described as a “graveyard for pharma.” But I believe we are now on the cusp of major breakthroughs in this field. If you look at the history of neuroscience therapeutics—from the lens of Roche—it illustrates this point well. In the 1960s, Roche developed benzodiazepines, starting with Librium and Valium. It then took another decade before launching Madopar for Parkinson’s disease, and two more decades before introducing tPA for acute stroke through Genentech, now part of Roche. For much of the 20th century, new classes of therapies in neuroscience were sparse—perhaps one every decade or two.Starting in 2017, that pace changed dramatically. We launched Ocrevus for multiple sclerosis, Evrysdi for spinal muscular atrophy, Enspryng for neuromyelitis optica spectrum disorders, and now Elevidys for Duchenne muscular dystrophy. That’s four major launches within a relatively short period—something we hadn’t seen before in this space. And this isn’t a coincidence; it signals that we’ve reached a real turning point.What excites me even more is that we’re now making meaningful progress in major prevalent disorders like Alzheimer’s disease and Parkinson’s disease—areas that have historically been incredibly challenging. In Alzheimer’s, we’re advancing trontinemab, which utilizes our innovative brain shuttle technology, and nivegacetor, a gamma secretase modulator. In Parkinson’s, we’re developing prasinezumab, which targets aggregated alpha-synuclein, a key pathological hallmark of the disease.Several factors are driving this progress. First, advances in human genetics have provided critical insights into disease mechanisms. Second, our understanding of disease biology has significantly improved. And third, new technological platforms are accelerating discovery and development. Together, these advances create a strong foundation for why we believe neuroscience therapeutics is entering a new era of meaningful progress.You mentioned both small molecules and antibodies. How does Roche approach modality selection when targeting CNS diseases?Azad Bonni: For a long time, small molecules have been the primary therapeutic approach in neuroscience, and they will certainly continue to play an important role. Small molecules offer several advantages, and there have been significant advances in this area in recent years.At the same time, large molecules—such as biologics—are becoming increasingly relevant. The main challenge with large molecules in neuroscience has always been the blood-brain barrier, which, while essential for protecting brain function, also makes it incredibly difficult for therapeutics to reach brain tissue. That’s where innovations like our brain shuttle technology come in. This platform allows us to effectively bypass the blood-brain barrier and deliver therapies directly to the brain, opening up entirely new possibilities for treating neurological diseases.So, to answer your question directly—there’s no one-size-fits-all approach. We need to apply multiple modalities and fully leverage the expanding range of therapeutic options to address the complex challenges of nervous system disorders. And that’s exactly what we’re doing at Roche and across the field.Many drug developers struggle with the translational ‘valley of death.’ What does Roche do differently to more effectively bridge early discovery and clinical development?Azad Bonni: Thanks to the scientific advances I mentioned earlier, we can now approach drug development in neuroscience in a fundamentally different—and more modern—way than in the past. This means focusing on diseases where there’s strong genetic evidence and a decent biological understanding of disease pathogenesis, and where we can apply cutting-edge technological platforms. In other words, we prioritize disease areas and targets that offer relatively high biological confidence. While we’re still in the early stages of translating that into clinically validated targets in neuroscience, we’re making steady progress.Another critical factor is improving the predictive validity of preclinical models—ensuring that what we learn in research better reflects what will happen in humans. That’s an ongoing effort. Equally important is the development of better biomarkers. Robust biomarkers are essential to guide decision-making along the value chain. Together, these factors—targeting high-confidence biology, improving translational models, and developing better biomarkers—are key to overcoming the “valley of death” you described.Many companies have historically focused on neuroscience, but over time the field lost momentum. Recently, however, we’ve seen a resurgence of activity and renewed enthusiasm. In your view, what’s fundamentally different this time, and what steps can be taken to avoid repeating the cycles of attrition we’ve seen in the past?Azad Bonni: That’s a great question, and I fully agree with you—there’s a clear renaissance happening in neuroscience, and I believe it will continue to accelerate throughout this decade and the next.One critical factor I want to highlight is the role of biomarkers. Take Alzheimer’s disease as an example. Despite more than 25 years of work on amyloid-targeting therapies and many high-profile failures, those setbacks led to significant advances in our understanding of the disease and in developing biomarkers. These biomarkers have fundamentally changed how we approach drug development. They allow us to ask precise scientific questions, both preclinically and in clinical trials, and enable proof-of-mechanism studies—helping us determine early on whether a drug is doing what it’s supposed to do before committing significant time and resources to later-stage development.This experimental medicine approach has been critical to the recent progress in Alzheimer’s, and we now need to apply that same mindset to other diseases—Parkinson’s and beyond. While there’s still more to do even in Alzheimer’s, the collaborative efforts of pharma, biotech, and academia have created a strong foundation through biomarker development. That model can—and should—be extended to other complex neurological diseases.Beyond biomarkers, what other technologies is Roche exploring that you believe could fundamentally transform how we discover and translate medicines over the next five years?Azad Bonni: One technology I’d really like to highlight is our brain shuttle platform. While there are many exciting technologies in development, I believe this one has the potential to fundamentally change how we deliver therapies to the brain. As I mentioned earlier, the blood-brain barrier prevents large molecules like antibodies from entering the brain. With conventional antibodies, typically only about 0.1% reaches the brain, and even then, the distribution is limited, often concentrated around the ventricles rather than throughout the brain tissue.The brain shuttle technology addresses this challenge by leveraging natural transcytosis mechanisms—the body’s way of transporting substances across the barrier. Through advanced protein engineering, we’ve developed molecules like trontinemab, an antibody that targets aggregated amyloid plaques in Alzheimer’s disease. Trontinemab is engineered to include a moiety that binds to the transferrin receptor, enabling it to actively cross the blood-brain barrier through transcytosis. Importantly, this engineering ensures that the antibody behaves properly both in peripheral circulation and once inside the brain, avoiding unwanted accumulation in endothelial cells lining the blood vessels.Trontinemab is currently our most advanced asset using this technology. In a Phase 2a trial, it demonstrated rapid and robust depletion of amyloid plaques, dramatically more than conventional antibodies. What’s also exciting is that it showed a lower incidence of ARIA (amyloid-related imaging abnormalities)—a common adverse effect seen with traditional amyloid therapies. We believe this may be related to the different route of entry into the brain.But the potential of the brain shuttle goes far beyond amyloid and Alzheimer’s disease. This platform can be applied to other antibodies, a range of neurological diseases, and even beyond antibodies to other modalities, opening up entirely new possibilities for treating diseases of the brain.For my final question—if you had a magic wand and could make one wish come true in neuroscience, what would it be?Azad Bonni: That’s a great question. One area I’ve been thinking about lately is preventive neurology. In cardiology, for example, prevention is already well established—with treatments like antihypertensives, statins, and now GLP-1 agonists aimed at addressing risk factors before serious disease develops. I believe we will approach a similar turning point in neurology.To give some context in the example of Alzheimer’s, by the sixth decade of life, it’s estimated that up to 40% of people already have amyloid pathology in the brain, even if they show no symptoms. Now imagine a future where accurate diagnostic tests identify these individuals early, and we have targeted therapies to prevent progression to symptomatic disease. This is the kind of future I’m excited about—and one I believe is increasingly within reach.At Roche, we’re uniquely positioned to lead this transformation because we have both a pharmaceutical and diagnostics division, and we’re global leaders in neurology across both areas. This gives us a unique ability to advance precision-type, preventive approaches that could fundamentally change how we manage neurological diseases. Of course, this doesn’t mean we’ll stop focusing on treatments for people who already have symptoms—that remains critical as long as unmet medical needs exist. But as societies become more focused on maintaining health and quality of life, secondary prevention—intervening before symptoms emerge—will become an increasingly important part of the future of medicine. And I’m truly excited to be part of shaping that future.免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

– Multiple Subgroup Analyses Presented From Long-Term Safety Study of LYBALVI® (olanzapine and samidorphan), Including Data on Lipid and Glycemic Profiles – DUBLIN , June 2, 2025 /PRNewswire/ -- Alkermes plc (Nasdaq: ALKS) today announced the presentation of accepted research at key scientific conferences this spring, including presentations largely related to its psychiatry products LYBALVI® (olanzapine and samidorphan) and ARISTADA® (aripiprazole lauroxil). Several of these meetings coincided with Mental Health Awareness Month in May, an important moment to raise awareness about mental health conditions, support the millions of people living with these complex diseases, and acknowledge the critical work of healthcare providers. The meetings included: American Association of Psychiatric Pharmacists (AAPP) Annual Meeting, April 27-30 , Salt Lake City The Neuroscience Education Institute (NEI) Spring Congress , May 8-10 , Philadelphia The Professional Society for Health Economics and Outcomes Research (ISPOR) Annual Conference, May 13-16 , Montreal American Psychiatric Association (APA), May 17-21 , Los Angeles American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, May 27-30 , Scottsdale Psych Congress Elevate, May 28-31 , Las Vegas "Alkermes is honored to present at these notable scientific meetings, sharing our research and insights with thought leaders and healthcare providers from across the field of psychiatry," said Craig Hopkinson , M.D., Chief Medical Officer and Executive Vice President, Research & Development at Alkermes. "Alkermes is committed to contributing to the advancement of patient care and the body of evidence in neuro-psychiatry, including for the treatment of schizophrenia and bipolar I disorder. We welcome the opportunity to have a voice at these important gatherings and connect with fellow stakeholders." Highlights of accepted presentations include: First presentation of an analysis of lipid and glycemic profiles across adult patient subgroups who received up to four years of treatment with LYBALVI in an open-label extension study. Analysis of safety, tolerability and durability of treatment effect across adult patient subgroups who received up to four years of treatment with LYBALVI in an open-label extension study. Findings from a post hoc evaluation of the effects of acute and long-term treatment with LYBALVI on negative symptoms of schizophrenia during a four-week study and a 52-week open-label extension study. Results of a post hoc examination of the efficacy and safety of ARISTADA every two months with varying baseline levels of severity of illness among adults with schizophrenia enrolled in a phase 3b study. The full list of Alkermes' presentations by meeting is as follows: AAPP Poster 318: Study Retention Rates in the Olanzapine/Samidorphan Phase 3 Clinical Program Poster 310: Treatment Patterns and Healthcare Resource Utilization of Patients With Schizophrenia Prescribed Aripiprazole Lauroxil Versus Oral Aripiprazole: A Retrospective Claims-Based Study NEI-Spring Poster 17: Treatment Effects of Olanzapine/Samidorphan on Negative Symptoms in Patients With Schizophrenia: A Post Hoc Analysis Poster 18: Baseline Severity of Illness and Response to Treatment With Aripiprazole Lauroxil Every 2 Months: A Post Hoc Analysis of Phase 3 ALPINE Clinical Trial Data ISPOR Poster 6031: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Schizophrenia Poster 6028: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Bipolar I Disorder Poster EE376: Treatment Patterns and Healthcare Resource Utilization of Patients Early in Schizophrenia Illness Initiating Aripiprazole Lauroxil Versus Oral Aripiprazole: A Retrospective Claims-Based Study Poster PCR242: The Economic Burden of Narcolepsy in the United States : Matched Analysis of National Health and Wellness Survey Data ASCP Poster T14: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Schizophrenia Poster T13: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Bipolar I Disorder Poster T56: Treatment Effects of Olanzapine/Samidorphan on Negative Symptoms in Patients With Schizophrenia: A Post Hoc Analysis Poster T57: Study Retention Rates in the Olanzapine/Samidorphan Phase 3 Clinical Program Poster T51: Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: A Patient Subgroup Analysis of a 4-Year Open-Label Study Poster W84: Lipid and Glycemic Profile of Olanzapine and Samidorphan: A Patient Subgroup Analysis of a 4-Year Open-Label Study Poster T58: Baseline Severity of Illness and Response to Treatment With Aripiprazole Lauroxil Every 2 Months: A Post Hoc Analysis of Phase 3 ALPINE Clinical Trial Data Psych Congress Elevate Poster 49: Safety, Tolerability, and Durability of Treatment Effect of Olanzapine and Samidorphan: A Patient Subgroup Analysis of a 4-Year Open-Label Study Poster 39: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Schizophrenia Poster 38: Healthcare Resource Utilization 12 Months Following Initiation of Olanzapine/Samidorphan: Real-World Assessment of Patients With Bipolar I Disorder Poster 31: Baseline Severity of Illness and Response to Treatment With Aripiprazole Lauroxil Every 2 Months: A Post Hoc Analysis of Phase 3 ALPINE Clinical Trial Data About LYBALVI® (olanzapine and samidorphan) LYBALVI® (olanzapine and samidorphan) is a once-daily, oral atypical antipsychotic drug approved in the U.S. for the treatment of adults with schizophrenia and for the treatment of adults with bipolar I disorder, as a maintenance monotherapy or for the acute treatment of manic or mixed episodes, as monotherapy or an adjunct to lithium or valproate. LYBALVI is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, in a single bilayer tablet. LYBALVI is available in fixed dosage strengths composed of 10 mg of samidorphan and 5 mg, 15 mg or 20 mg of olanzapine. IMPORTANT SAFETY INFORMATION for LYBALVI® (olanzapine and samidorphan) Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LYBALVI is not approved for the treatment of patients with dementia-related psychosis. Contraindications: LYBALVI is contraindicated in patients who are using opioids or are undergoing acute opioid withdrawal. If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for the contraindications for these products. Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke, transient ischemia attack, and fatalities. See Boxed Warning. Precipitation of Severe Opioid Withdrawal in Patients who are Physiologically Dependent on Opioids: LYBALVI can precipitate opioid withdrawal in patients who are dependent on opioids, which can lead to an opioid withdrawal syndrome, sometimes requiring hospitalization. LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Prior to initiating LYBALVI, there should be at least a 7‑day opioid-free interval from last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. Explain the risks associated with precipitated withdrawal and the importance of giving an accurate account of last opioid use to patients and caregivers. Vulnerability to Life-Threatening Opioid Overdose: Attempting to overcome opioid blockade with high or repeated doses of exogenous opioids could lead to life-threatening or fatal opioid intoxication, particularly if LYBALVI therapy is interrupted or discontinued, subjecting the patient to high levels of unopposed opioid agonist as the samidorphan blockade wanes. Inform patients of the potential consequences of trying to overcome the opioid blockade and the serious risks of taking opioids concurrently with LYBALVI or while transitioning off LYBALVI. In emergency situations, if a LYBALVI-treated patient requires opioid treatment as part of anesthesia or analgesia, discontinue LYBALVI. Opioids should be administered by properly trained individual(s) and patient should be continuously monitored in a setting equipped and staffed for cardiopulmonary resuscitation. Patients with a history of chronic opioid use prior to treatment with LYBALVI may have decreased opioid tolerance if LYBALVI therapy is interrupted or discontinued. Advise patients that this decreased tolerance may increase the risk of opioid overdose if opioids are resumed at the previously tolerated dosage. Neuroleptic Malignant Syndrome, a potentially fatal reaction. Signs and symptoms include hyperpyrexia, muscle rigidity, delirium, autonomic instability, elevated creatine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and close monitoring. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a potentially fatal condition reported with exposure to olanzapine, a component of LYBALVI. Symptoms include a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue if DRESS is suspected. Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Any patient treated with LYBALVI should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required anti-diabetic treatment despite discontinuation of the suspect drug. Measure weight and assess fasting glucose and lipids when initiating LYBALVI and monitor periodically. Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible increases with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after discontinuation. Given these considerations, LYBALVI should be prescribed in a manner that is most likely to reduce the risk of tardive dyskinesia. If signs and symptoms of TD appear, drug discontinuation should be considered. Orthostatic Hypotension and Syncope: Monitor orthostatic vital signs in patients who are vulnerable to hypotension, patients with known cardiovascular disease, and patients with cerebrovascular disease. Falls: LYBALVI may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls, and consequently, fractures or other injuries. Assess patients for risk when using LYBALVI. Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases): Perform complete blood counts in patients with a history of a clinically significant low white blood cell (WBC) count or history of leukopenia or neutropenia. Discontinue LYBALVI if clinically significant decline in WBC occurs in the absence of other causative factors. Dysphagia: Use LYBALVI with caution in patients at risk for aspiration. Seizures: Use LYBALVI with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Because LYBALVI may cause somnolence, and may impair judgment, thinking, or motor skills, caution patients about operating hazardous machinery, including motor vehicles, until they are certain that LYBALVI does not affect them adversely. Body Temperature Dysregulation: Use LYBALVI with caution in patients who may experience conditions that increase core body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics). Anticholinergic (Antimuscarinic) Effects: Olanzapine, a component of LYBALVI, was associated with constipation, dry mouth, and tachycardia. Use LYBALVI with caution with other anticholinergic medications and in patients with urinary retention, prostatic hypertrophy, constipation, paralytic ileus or related conditions. In postmarketing experience, the risk for severe adverse reactions (including fatalities) was increased with concomitant use of anticholinergic medications. Hyperprolactinemia: LYBALVI elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Risks Associated with Combination Treatment with Lithium or Valproate: If LYBALVI is administered with lithium or valproate, refer to the lithium or valproate Prescribing Information for a description of the risks for these products. Interference with Laboratory Tests for Opioid Detection: LYBALVI may cause false positive results with urinary immunoassay methods for detecting opioids. Use an alternative analytical technique (e.g., chromatographic methods) to confirm positive opioid urine drug screen results. Most Common Adverse Reactions observed in clinical trials were: Schizophrenia (LYBALVI): weight increased, somnolence, dry mouth, and headache Bipolar I Disorder, Manic or Mixed Episodes (olanzapine): somnolence, dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite, and tremor Bipolar I Disorder, Manic or Mixed Episodes, adjunct to lithium or valproate (olanzapine): dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia Concomitant Medication: LYBALVI is contraindicated in patients who are using opioids or undergoing acute opioid withdrawal. Concomitant use of LYBALVI is not recommended with strong CYP3A4 inducers, levodopa and dopamine agonists. Reduce dosage of LYBALVI when using with strong CYP1A2 inhibitors. Increase dosage of LYBALVI with CYP1A2 inducers. Use caution with diazepam, alcohol, other CNS acting drugs, or in patients receiving anticholinergic (antimuscarinic) medications. Monitor blood pressure and reduce dosage of antihypertensive drug in accordance with its approved product labeling. Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with LYBALVI. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LYBALVI during pregnancy. Renal Impairment: LYBALVI is not recommended for patients with end-stage renal disease (eGFR of <15 mL/minute/1.73 m2). To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-888-235-8008 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please click here for full Prescribing Information, including Boxed Warning, for LYBALVI. About ARISTADA® (aripiprazole lauroxil) Extended-Release Injectable Suspension, for Intramuscular Use ARISTADA® is indicated for the treatment of schizophrenia in adults. ARISTADA is in injectable atypical antipsychotic approved in four dose strengths and three dosing durations for the treatment of schizophrenia in adults (441 mg, 662 mg or 882 mg monthly, 882 mg once every six weeks and 1064 mg once every two months). Once in the body, ARISTADA converts to aripiprazole. About ARISTADA INITIO® (aripiprazole lauroxil) Extended-Release Injectable Suspension, for Intramuscular Use ARISTADA INITIO®, in combination with oral aripiprazole, is indicated for the initiation of ARISTADA when used for the treatment of schizophrenia in adults. ARISTADA INITIO, in combination with a single 30 mg dose of oral aripiprazole, is indicated for the initiation of ARISTADA when used for the treatment of schizophrenia in adults. The first ARISTADA dose may be administered on the same day as the ARISTADA INITIO regimen or up to 10 days thereafter. IMPORTANT SAFETY INFORMATION for ARISTADA INITIO® and ARISTADA® WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ARISTADA INITIO and ARISTADA are not approved for the treatment of patients with dementia-related psychosis. Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis. Cerebrovascular Adverse Reactions, Including Stroke: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, have been reported in placebo-controlled trials of elderly patients with dementia-related psychosis treated with risperidone, aripiprazole, and olanzapine. ARISTADA INITIO and ARISTADA are not approved for the treatment of patients with dementia-related psychosis. Potential for Dosing and Medication Errors: Medication errors, including substitution and dispensing errors, between ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is intended for single administration in contrast to ARISTADA which is administered monthly, every 6 weeks, or every 8 weeks. Do not substitute ARISTADA INITIO for ARISTADA because of differing pharmacokinetic profiles. Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex may occur with administration of antipsychotic drugs, including ARISTADA INITIO and ARISTADA. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing antipsychotics should be consistent with the need to minimize TD. Discontinue ARISTADA if clinically appropriate. TD may remit, partially or completely, if antipsychotic treatment is withdrawn. Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include: Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics. There have been reports of hyperglycemia in patients treated with oral aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug. Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics. Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended. Pathological Gambling and Other Compulsive Behaviors: Compulsive or uncontrollable urges to gamble have been reported with use of aripiprazole. Other compulsive urges less frequently reported include sexual urges, shopping, binge eating and other impulsive or compulsive behaviors which may result in harm for the patient and others if not recognized. Closely monitor patients and consider dose reduction or stopping aripiprazole if a patient develops such urges. Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension which can be associated with dizziness, lightheadedness, and tachycardia. Monitor heart rate and blood pressure, and warn patients with known cardiovascular or cerebrovascular disease and risk of dehydration and syncope. Falls: Antipsychotics including ARISTADA INITIO and ARISTADA may cause somnolence, postural hypotension or motor and sensory instability which may lead to falls and subsequent injury. Upon initiating treatment and recurrently, complete fall risk assessments as appropriate. Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia and agranulocytosis have been reported with antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue ARISTADA INITIO and/or ARISTADA at the first sign of a clinically significant decline in WBC and in severely neutropenic patients. Seizures: Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: ARISTADA INITIO and ARISTADA may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are certain therapy with ARISTADA INITIO and/or ARISTADA does not affect them adversely. Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Advise patients regarding appropriate care in avoiding overheating and dehydration. Appropriate care is advised for patients who may exercise strenuously, may be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or are subject to dehydration. Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use; use caution in patients at risk for aspiration pneumonia. Concomitant Medication: ARISTADA INITIO is only available at a single strength as a single-dose pre-filled syringe, so dosage adjustments are not possible. Avoid use in patients who are known CYP2D6 poor metabolizers or taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers, antihypertensive drugs or benzodiazepines. Depending on the ARISTADA dose, adjustments may be recommended if patients are 1) known as CYP2D6 poor metabolizers and/or 2) taking strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or strong CYP3A4 inducers for greater than 2 weeks. Avoid use of ARISTADA 662 mg, 882 mg, or 1064 mg for patients taking both strong CYP3A4 inhibitors and strong CYP2D6 inhibitors. (See Table 4 in the ARISTADA full Prescribing Information.) Commonly Observed Adverse Reactions: In pharmacokinetic studies the safety profile of ARISTADA INITIO was generally consistent with that observed for ARISTADA. The most common adverse reaction (≥5% incidence and at least twice the rate of placebo reported by patients treated with ARISTADA 441 mg and 882 mg monthly) was akathisia. Injection Site Reactions: In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection site reactions with ARISTADA INITIO were similar to the incidence observed with ARISTADA. Injection site reactions were reported by 4%, 5%, and 2% of patients treated with 441 mg ARISTADA (monthly), 882 mg ARISTADA (monthly), and placebo, respectively. Most of these were injection site pain and associated with the first injection and decreased with each subsequent injection. Other injection site reactions (induration, swelling, and redness) occurred at less than 1%. Dystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first days of treatment and at low doses. Pregnancy/Nursing: Neonates exposed to antipsychotic drugs, including ARISTADA INITIO and ARISTADA, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Advise patients to notify their healthcare provider of a known or suspected pregnancy. Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA INITIO and/or ARISTADA during pregnancy. Aripiprazole is present in human breast milk. Aripiprazole exposure during pregnancy and/or the postpartum period may decrease milk supply. Monitor the breastfed infant for dehydration and lack of appropriate weight gain. The benefits of breastfeeding should be considered along with the mother's clinical need for ARISTADA INITIO and/or ARISTADA and any potential adverse effects on the infant from ARISTADA INITIO and/or ARISTADA or from the underlying maternal condition. To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at 1-866-274-7823 or FDA at 1-800-FDA-1088 or https://www.fda.gov/medwatch. Please see accompanying full Prescribing Information, including Boxed Warning, for ARISTADA INITIO and ARISTADA. About Alkermes plc Alkermes plc is a global biopharmaceutical company that seeks to develop innovative medicines in the field of neuroscience. The company has a portfolio of proprietary commercial products for the treatment of alcohol dependence, opioid dependence, schizophrenia and bipolar I disorder, and a pipeline of clinical and preclinical candidates in development for neurological disorders, including narcolepsy and idiopathic hypersomnia. Headquartered in Ireland, Alkermes also has a corporate office and research and development center in Massachusetts and a manufacturing facility in Ohio. For more information, please visit Alkermes' website at www.alkermes.com. Alkermes Contacts:For Investors: Sandy Coombs, +1 781 609 6377For Media: Marisa Borgasano, +1 781 609 6659 View original content to download multimedia:https://www.prnewswire.com/news-releases/alkermes-highlights-data-from-psychiatry-portfolio-at-spring-2025-scientific-conferences-302469723.html SOURCE Alkermes plc