Zuranolone

CAMBRIDGE, Mass., July 25, 2025 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending marketing authorization for ZURZUVAE® (zuranolone) for the treatment of postpartum depression (PPD) in adults following childbirth. If approved by the European Commission (EC), ZURZUVAE will be the first treatment authorized within the European Union specifically indicated to treat depressive symptoms for women with PPD. ZURZUVAE is a once-daily, oral, 14-day treatment which was approved by the U.S. Food and Drug Administration (FDA) in 2023. “This is an important milestone for maternal health in the European Union,” said Priya Singhal, M.D., M.P.H., Head of Development at Biogen. “ZURZUVAE represents a novel therapeutic approach for the targeted treatment of postpartum depression, with data demonstrating potential for symptom improvement as early as day three of a 14-day course. If approved, this represents a significant opportunity to advance the treatment of a serious condition that remains both underdiagnosed and undertreated.” PPD is one of the most common medical conditions associated with pregnancy.1-3 Symptoms of PPD may include depressed mood, anxiety, affected ability to bond with the newborn, functional impairment of daily activities, feelings of guilt and worthlessness, doubts about motherhood, and thoughts of self- or infant harm.1 Left untreated, PPD symptoms may persist beyond the postpartum period and can lead to prolonged maternal morbidities and repercussions on child development.4-6 In Europe, an estimated 5-20% of women with a pregnancy experience symptoms of PPD.7-12 Because clinical guidelines for screening and management of depression during and after pregnancy vary across European countries, many cases may go undiagnosed and untreated.3 Death by suicide during the perinatal period is a leading cause of maternal mortality in Europe.4, 13 The CHMP’s recommendation for ZURZUVAE is based on the SKYLARK Study evaluating ZURZUVAE which met its primary endpoint, a significant mean reduction from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, a common measure of depression severity, at Day 15 as compared to placebo. All key secondary endpoints were also met, with significant reduction in depressive symptoms seen as early as Day 3 and sustained through Day 45 compared to placebo. ZURZUVAE was generally well-tolerated. The most frequently reported side effects ≥ 5% and greater than placebo in patients treated with ZURZUVAE 50 mg were somnolence, dizziness, and sedation. The CHMP’s recommendation for ZURZUVAE will now be reviewed by the EC for marketing authorization in the European Union with a final decision expected in the third quarter of 2025. The U.S. FDA approved ZURZUVAE in August 2023 and the Drug Enforcement Agency (DEA) scheduled it as a Class IV controlled substance on October 31, 2023. About ZURZUVAE® (zuranolone)In the U.S., ZURZUVAE® is a once-daily, oral, 14-day medicine for treatment of postpartum depression (PPD) in adults. ZURZUVAE is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. ZURZUVAE was discovered by Sage Therapeutics, Inc. (Nasdaq: SAGE), and in 2020 Biogen and Sage Therapeutics entered into a collaboration to jointly develop and commercialize ZURZUVAE in the U.S. As part of the agreement, Biogen received exclusive rights to develop and commercialize ZURZUVAE outside of the U.S., excluding Japan, Taiwan and South Korea. About BiogenFounded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, including relating to; the potential, benefits, safety and efficacy of zuranolone (marketed under the brand name ZURZUVAE); the potential of Biogen’s commercial business and pipeline programs, including ZURZUVAE; the anticipated benefits and potential of Biogen’s collaboration arrangement with Sage; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “goal,” “guidance,” “hope,” “intend,” “may,” “objective,” “plan,” “possible,” “potential,” “predict,” “project,” “prospect,” “should,” “target,” “will,” “would,” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements. Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements. These forward-looking statements are based on management's current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to be materially different from those stated or implied in this document, including, among others, uncertainty of long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans and prospects relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; our ability to effectively implement our corporate strategy; the successful execution of our strategic and growth initiatives, including acquisitions; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in other reports we have filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q and Form 10-K, in each case including in the sections thereof captioned “Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in our subsequent reports on Form 8-K. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise. References: American Psychiatric Association, Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596. 5 ed. 2013, Washington, DC. Vigod, S.N., et al., Canadian Network for Mood and Anxiety Treatments 2024 Clinical Practice Guideline for the Management of Perinatal Mood, Anxiety, and Related Disorders: Guide de pratique 2024 du Canadian Network for Mood and Anxiety Treatments pour le traitement des troubles de l'humeur, des troubles anxieux et des troubles connexes perinatals. Can J Psychiatry, 2025: p. 7067437241303031. Motrico, E., et al., Clinical practice guidelines with recommendations for peripartum depression: A European systematic review. Acta Psychiatr Scand, 2022. 146(4): p. 325-339. The Lancet Regional, H.-E., Support not stigma: redefining perinatal mental health care. Lancet Reg Health Eur, 2024. 40: p. 100930. Slomian, J., et al., Consequences of maternal postpartum depression: A systematic review of maternal and infant outcomes. Womens Health (Lond), 2019. 15: p. 1745506519844044. Rogers, A., et al., Association Between Maternal Perinatal Depression and Anxiety and Child and Adolescent Development: A Meta-analysis. JAMA Pediatr, 2020. 174(11): p. 1082-1092. Clavenna, A., et al., Postnatal depression screening in a paediatric primary care setting in Italy. BMC Psychiatry, 2017. 17(1): p. 42. Cena, L., et al., Prevalence of maternal antenatal and postnatal depression and their association with sociodemographic and socioeconomic factors: A multicentre study in Italy. J Affect Disord, 2021. 279: p. 217-221. Della Corte, L., et al., Prevalence and associated psychological risk factors of postpartum depression: a cross-sectional study. J Obstet Gynaecol, 2022. 42(5): p. 976-980. Pataky, E.A. and U. Ehlert, Longitudinal assessment of symptoms of postpartum mood disorder in women with and without a history of depression. Arch Womens Ment Health, 2020. 23(3): p. 391-399. Dekel, S., et al., The dynamic course of peripartum depression across pregnancy and childbirth. J Psychiatr Res, 2019. 113: p. 72-78. Holm, D.L., et al., A quantitative comparison of two measures of postpartum depression. BMC Psychiatry, 2022. 22(1): p. 202. Diguisto, C., et al., Maternal mortality in eight European countries with enhanced surveillance systems: descriptive population based study. BMJ, 2022. 379: p. e070621.

同写意年度巨献！！7月24-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！纽欧申医药创始人、CEO申华琼将参与“CNS新药开发”分会并作报告《CNS创新药的研发热点和布局思路》，敬请期待！在CNS领域，“全新靶点”的突破往往源于对已知生物机制的精细化调控——神经递质系统等基础框架虽已明确，但通过对受体亚型、分子结构的精准微调，仍能催生出具有颠覆性疗效的创新药物。这一“以微调求突破”的研发逻辑，正成为当下CNS领域创新的核心驱动力。本文将从临床需求缺口切入，解析CNS药物研发的底层逻辑，通过强生高价收购Intra-Cellular、BMS引进KarXT等典型案例揭示，为行业提供从靶点验证到临床转化的全链条参考。TONACEA01精神类药物成为继肿瘤之后的第二热门治疗领域图1保守估计，人一生中约1/3时期可能出现抑郁情绪障碍，实际受影响人群上亿，背后是大量未被充分关注的情绪健康问题。伴随老龄化加剧（如上海人均寿命将达90岁），90岁老人约1/3有认知功能减退，患上阿尔兹海默症，给医疗照护带来沉重负担。精神分裂症患病率为0.5%-1%，帕金森病是重大社会负担，二者治疗均非常不足，精神分裂症对阴性症状、认知功能改善基本无有效药物。虽然CNS领域新药虽不断涌现，但能有效覆盖的患者不足30%，多数患者治疗效果有限，这也凸显该领域巨大的未满足需求与研发价值。也常有人质疑“小分子还有啥可做，似已至瓶颈”，数据却呈现出不同现状：当下CNS新药研发里，小分子药物独占鳌头，占比超70%；生物制品占比23%，虽逐渐增多，但目前仍为小分子主导研发格局，这就是该领域当前的研发状态。图2近十余年，CNS药物在FDA批准新药中常居第二或第三位。2023-2024年，CNS领域有诸多突破：阿尔兹海默领域，Lecanemab、Donanemab两款单抗获批，它们的成功源于几代人探索，前期失败也为如今奠基。精神分裂症等适应症方面，像针对产后抑郁的Zuranolone，其靶点（GABA-A受体）不新，但适应症是全球独有；还有KarXT（Cobenfy），通过巧妙组合，让新靶点成药性得以实现，这些都彰显CNS领域新药研发的活力与突破。当前，CNS疾病治疗领域受生物技术/制药公司、监管机构和资本市场共同推动，但投资圈仍存在“想投却不知咋投”的纠结现状。只因CNS研发有独特性，若未曾经历研发就很难从主观症状找客观规律、判断研发方向，近年资本寒冬也让大家更谨慎。对于这些疑问，我们可以通过以下三个案例进行分析。TONACEA02强生高价收购Intra-Cellular公司近期，强生以146亿美金收购Intra-Cellular加入商业策略来上市产品充实管线，看好CNS精神药物领域。这表明在CNS领域，并非只有全新靶点才能成功，临床端能有效交付成果，策略巧妙也可达成目标。Caplyta（芦玛哌酮）虽看似不“亮眼”，其临床信号也并非突出，但发展历程与市场表现值得关注。2019年其首发适应症为精神分裂症，2021年全球首次获批用于双相抑郁，解决了双相抑郁治疗棘手的临床问题。常用的抗抑郁药容易引发躁狂相，而目前常用的治疗双击情感障碍的药（很多是抗精神病的药物适应症扩展而来）副作用很多，病人耐受性差，比如引发内分泌紊乱等从而导致长期用药依从性差等难题。图3Caplyta的探索逻辑，是从临床未被满足需求（如双相抑郁治疗）中，找“较窄而精准”的突破点，用快速适应症扩展来覆盖临床缺口，体现了对这个领域的深刻理解与药物研发上的灵活推进。此外，Caplyta还向FDA递交了用于重度抑郁症辅助治疗的申请。这些都是对在该领域急需上市产品来填补缺口的强生具有极大吸引力的地方。既然都说Caplyta是一个失败的试验，那它怎么还上市了呢？其实支撑它上市的是三项临床试验，分别是Ⅱ期的005、Ⅲ期的301和302。在精神神经科领域，FDA通常要求有两个阳性结果，所以大公司一般会设计至少三项注册试验，争取两个成功。就Caplyta而言，005和301是阳性结果，302虽有696名患者、时长6周且结果阴性，但失败有特殊原因，比如安慰剂反应异常高，一定的有效性趋势，阳性对照药也没有做出应有的显著性差异等情况。相信这些都是和FDA反复认真分析讨论过的，最终是Totality of evidence （整体证据）得以让该产品上市。所以CNS药物的临床研发策略，技巧和实施至关重要。TONACEA03靶向毒蕈碱受体的药物开发成为热点在精神分裂症治疗领域，目前尚无获批（FDA）用于治疗阴性症状的药物，现有治疗手段效果有限，这一现状凸显出巨大缺口。但需注意的是，新药研发不一定非要在阳性症状控制上超越前代药物，关键是填补一代、二代药物无法满足的需求（如存在注意力缺陷、记忆力受损、信息处理速度降低等认知功能问题以及内分泌，心血管副反应等问题），提升患者的生活质量减少长期用药的并发症。KarXT（xanomeline-trospium) （商品名叫Cobenfy），通过双重激动M1/M4受体，成功获批用于治疗精神分裂症，显示出对阳性和阴性症状的显著改善，进而弥补了这一缺口。虽然毒蕈碱受体这个靶点早期成药性并不好，但毒蕈碱受体相关的M1、M4机制经长期探索后如今备受认可。图4最初，礼来在KarXT研发阶段，发现绝大多数患者无法耐受，项目只好终止，后经低价转让和巧妙改进，即引入对抗M1外周副作用的制剂，把不良反应降低了很多。这是一个很好的例子说明，一个靶点的成败需要很多成药性的挖掘，要持续探索、多维度优化，只有通过不断认识和改进，才能让看似“弃子”的药物，逆袭成First-in-class的宝贝。KarXT从早期研发停止到后来被Karuna引进优化、推动上市等成功历程，就是很好的验证。在精神分裂症患者中，脑内神经递质系统失衡，尤其是多巴胺和乙酰胆碱系统的功能紊乱被认为是重要的病理机制之一。M4受体作为乙酰胆碱系统的重要组成部分，其功能异常被广泛认为参与了精神分裂症的发病过程，因此靶向M4受体有可能纠正这种神经递质失衡，为治疗精神分裂症提供新的途径。而M1多被认为与认知功能有关，由于外周分布多，很难做到提升在脑部的作用而又不导致难以耐受的外周的副作用，一直成药性差。而M4的分布主要在脑部，增加M4的剂量就比较容易让其在脑部的抗精神病的作用提升而不明显的增加副作用。但近期，M4靶点研究出现意外情况。比如针对 Emraclidine（CVL - 231 ）的研究，其 1b 期临床试验，效果很不错，患者的PANSS总分在统计学和临床意义上均有明显改善。与安慰剂相比，Emraclidine的总体耐受性良好。然而，Emraclidine在两项针对精神分裂症患者的Ⅱ期临床试验中却失败了。据艾伯维自己解释（也是我们理解的原因）一是部分试验中心实施不当，剔除表现差的中心后，Ⅱ期试验呈现明显有效信号；二是药物药代动力学个体变异大，约20%患者药物浓度低于检测线。这说明剂量不够（2期试验用的是30毫克/每天）。针对这些问题，艾伯维决定重新在健康受试者中探索，通过增加剂量，解决部分患者药物浓度不达标的情况。同时，针对阿尔兹海默症的精神症状，将老年健康者中开展多剂量探索研究，计划2026年完成。由上可见，虽然M4靶点药物研发存有失败案例（如Emraclidine），并不等于该靶点的失败，这和临床研发的多种因素有关。要知道当初礼来研发的杜勒西丁在二期的时候也有两个二期试验是失败的。从别的大公司的探索积累的经验教训可以让我们少走弯路。作为Biotech，我们会从这些成败中汲取经验，不被单一结果吓退，凭借对靶点，临床实际情况的理解、研发能力的积累，合理的规划布局在全球具有竞争力的针对精神神经领域疾病的多种候选药的研发，争取走在行业前列，实实在在解决未满足的临床需求。由纽欧申医药自主研发具有全球专利的选择性M4正向变构调节剂（NS-136），在临床前研究中显示出对阴性症状和认知功能的明显改善。在澳大利亚和中国人群中开展的一期临床试验显示不仅安全窗大很多，也未出现部分患者药物浓度低于检测线的问题，我们的剂量也远远超过Emraclidine。同时在老年患者群体的爬坡试验进展顺利。近期我们已经启动探索精神病疗效与安全性的二期临床试验。有关老年痴呆伴随精神或激越症状的二期临床试验也会在不久的将来开展。医学博士，科学博士美国精神心理科执照医生，曾任印第安纳大学医学院兼职教授，现任北京大学医学院客座教授；历任礼来研发部临床研究医师；惠氏制药医学总监；辉瑞制药全球资深总监、辉瑞制药中国临床研究负责人，首任恒瑞医药首席医学官；强生旗下杨森制药中国药物开发中心总负责、全球副总裁；天境生物研发总裁、首席执行官。曾当选全球行业知名媒体Endpoints New 2021年度“生物制药研发领域20位杰出女性”，2021年福布斯“中国科技女性榜”50人榜单及2022年百华协会年度女性领导者奖。