Zorevunersen sodium

– Data from an analysis designed to evaluate the potential effects of the Phase 3 zorevunersen dosing regimen showed improvements in cognition and behavior at Week 68 – – These findings support the inclusion of key secondary endpoints assessing cognition and behavior in the Phase 3 EMPEROR study and contrast with outcomes observed in natural history data – CAMBRIDGE, Mass. and BEDFORD, Mass., July 10, 2025 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) and Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced the presentation of data from an analysis that informed the design of the Phase 3 EMPEROR study and evaluated the potential effects of the Phase 3 zorevunersen dosing regimen. The data are complementary to previously reported data from a broader cohort of patients treated with zorevunersen in the Phase 1/2a and open label extension (OLE) studies that showed improvements within the first 9 months and continuing improvements through an additional two years. The new analysis is best aligned with the timing and dosing regimen that will be evaluated in the pivotal Phase 3 EMPEROR study and showed improvements in multiple measures of cognition and behavior at Week 68. The results contrasted with findings from a natural history study in which patients with Dravet syndrome were treated with standard of care medicines. Zorevunersen is in development as a first-in-class potential disease modifying treatment for Dravet syndrome. Results were presented as part of the Epilepsy II session at the 16th European Paediatric Neurology Society (EPNS) Congress. "Dravet syndrome is a complex neurodevelopmental disorder that has significant impacts on patients and their families,” said Dr. Andreas Brunklaus, Consultant Paediatric Neurologist at the Royal Hospital for Children in Glasgow, Honorary Professor at the University of Glasgow, and a zorevunersen study investigator. “Natural history data shows the limitations of treating this disease with anti-seizure medicines. The zorevunersen data give us early evidence that this new genetically-targeted approach could address the underlying cause of Dravet syndrome, resulting in additional seizure control and offer patients the opportunity to experience improvements in cognition and behavior." Previously presented data from the two Phase 1/2a and OLE studies showed substantial and durable reductions in major motor seizure frequency on top of a background of standard anti-seizure medicines and improvements in multiple measures of cognition and behavior through two years of treatment in the OLE studies. Data indicated responses may be better among patients who were treated with loading doses of 70mg followed by maintenance doses of 45mg. Zorevunersen was generally well-tolerated across these studies. "Effects on behavior and cognition are a key secondary endpoint in our Phase 3 EMPEROR study," said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “Feedback from caregivers and clinicians, and analyses like this one, give us insight into which assessments have the greatest potential to demonstrate meaningful effects for patients within the year-long treatment period.” “Most patients with Dravet syndrome continue to experience seizures despite treatment with the best available anti-seizure medicines, and there are currently no medications approved that address the underlying cognitive and behavioral aspects of the disease,” said Katherine Dawson, M.D., Head of the Therapeutics Development Unit at Biogen. “We look forward to continuing to work together to advance zorevunersen as a potential first-in-class disease modifying medicine for Dravet syndrome.” Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) that is characterized by severe, recurrent seizures as well as significant cognitive and behavioral impairments. There are no approved disease-modifying therapies for people living with Dravet syndrome. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the United States (~16,000), United Kingdom, EU-4 (Germany, France, Italy, Spain) and Japan.1 Description of the Modeled AnalysisA mixed-effects model for repeated measures (MMRM) analysis was used to evaluate the potential effects of the Phase 3 zorevunersen dosing regimen on patient cognition and behavior at Week 68. The model was developed using clinical data from patients in the Phase 1/2a ADMIRAL study and the LONGWING OLE study. An analysis of patients who received a total cumulative dose consistent with the Phase 3 EMPEROR regimen of two loading doses of 70mg followed by two maintenance doses of 45mg, showed improvements in cognition and behavior. The analysis was performed to inform the design of the Phase 3 EMPEROR study. Baseline covariates for patients followed in the BUTTERFLY natural history study were matched to the selected ADMIRAL patient population. Improvements in patients treated with zorevunersen contrasted with findings from BUTTERFLY. These data support the selection of five sub-domains of the Vineland-3 Adaptive Behavior Scales, including Receptive Communication, Expressive Communication, Interpersonal Relationships, Coping Skills, and Personal Skills now under evaluation as key secondary endpoints in the Phase 3 EMPEROR study. Details of the presentation are as follows: Title: Zorevunersen demonstrates potential as a disease modifying therapy in patients with Dravet syndrome through durable seizure reduction and improvements in cognition, behavior, and functioning with up to 24 months of maintenance dosing in open-label extension studiesPresenter: Andreas Brunklaus, M.D., Consultant Paediatric Neurologist at the Royal Hospital for Children, Glasgow, Honorary Professor at the University of GlasgowSession: Epilepsy IIDate/Time: Thursday, July 10, 11:51 AM CESTLocation: Saal 5, International Congress Center München, Germany The presentation will be available for download on the Stoke Therapeutics website under the Investors & News tab. About Dravet SyndromeDravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by severe, recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. More than 90 percent of patients continue to experience seizures despite treatment with the best available anti-seizure medicines. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan.1 About Zorevunersen Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing NaV1.1 protein production in brain cells from the non-mutated (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition, and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights. About Stoke TherapeuticsStoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/. 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. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; and the design, timing and results of the Phase 3 EMPEROR study. Statements including words such as “anticipate,” “could,” “expect,” “plan,” “will,” or “may” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause Stoke’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: Stoke’s ability to advance, obtain regulatory approval and ultimately commercialize its product candidates; that if Stoke’s collaborators were to breach or terminate their agreements, it would not obtain the anticipated financial or other benefits; the possibility that Stoke and Biogen may not be successful in their development of zorevunersen and that, even if successful, they may be unable to successfully commercialize zorevunersen; positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; Stoke’s ability to protect its intellectual property; Stoke’s ability to fund development activities and achieve development goals through mid-2028; and the other risks and uncertainties described under the heading “Risk Factors” in Stoke’s Annual Report on Form 10-K for the year ended December 31, 2024, its quarterly reports on Form 10-Q, and the other documents it files with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Stoke undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Biogen Safe Harbor This press release contains forward-looking statements, relating to: our strategy and plans; the potential of, and expectations for, our commercial business and pipeline programs; clinical development programs, clinical trials, and data readouts and presentations; regulatory discussions, submissions, filings, and approvals; the potential benefits, safety, and efficacy of our and our collaboration partners’ products and investigational therapies; and actions to improve the risk profile and productivity of R&D pipeline, collaborations, and business development activities. 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,” “outlook,” “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. This press release includes, among others, forward-looking statements including relating to: the ability of zorevunersen to treat the underlying causes of Dravet syndrome, the design, timing and results of the Phase 3 EMPEROR study and the potential effects of the Phase 3 zorevunersen dosing regimen. 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. 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 , 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. Reference: Stoke Media & Investor Contacts:Dawn KalmarChief Communications Officerdkalmar@stoketherapeutics.com 781-303-8302 Doug SnowDirector, Communications & Investor RelationsIR@stoketherapeutics.com 508-642-6485 Biogen Media Contact:Allison MurphyPublic.affairs@biogen.com+ 1 781 464 3260 Biogen Investor Contact:Tim PowerIR@biogen.com+1 781 464 2442

同写意年度巨献！！大会特设“CNS新药开发”分会，7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！渤健正式涉足RNAi领域。5月27日，渤健与成立仅7个月的RNAi技术公司City Therapeutics达成协议，共同开发新型中枢神经系统疗法。这家公司由数名前Alnylam高管创立，将运用其RNAi工程能力，与渤健共同开发新型中枢神经系统疗法。根据协议，City将获得1600万美元预付款和3000万美元的投资，并有资格获得高达10亿美元的里程碑付款以及销售分成。此次合作发生在强生、艾伯维披露在CNS研发中的失败消息，辉瑞、安进、默沙东等药企相继缩减CNS投入，以及阿斯利康表示不再碰CNS的背景下。这是渤健寻求“外部机遇”战略转型的需要，但在高风险的CNS领域，能否获得高收益，仍需打一个问号。TONACEA01关键武器在渤健与City的合作中，RNAi技术成为解决CNS疾病的关键武器。这种技术通过沉默致病基因表达，为传统药物难以靶向的疾病靶点提供新解决方案。自2018年首款RNAi药物patisiran获批以来，全球已有近10款siRNA药物获批上市。据Evaluate Pharma数据，全球siRNA药物市场规模已突破50亿美元，预计2030年将达200亿美元。CNS领域应用RNAi技术长期面临血脑屏障的递送挑战。渤健将贡献其专有药物递送技术，与City的下一代RNAi工程技术平台结合，开发针对CNS疾病靶点的RNAi触发分子。City执行主席John Maraganore是RNAi治疗领域的先驱，曾领导Alnylam将首款RNAi疗法推向市场。渤健研发负责人Jane Grogan在合作声明中强调，此次合作突显了公司新的战略研究方法，即平衡差异化的内部能力与对尖端科学的外部投资。“我们正在扩展研发工具箱中的药物形式，通过添加基于RNAi的方法，更精确地实现目标。”Grogan道出渤健转型的核心。两年前，渤健就提出“Fit for Growth”计划，希望通过优化资源配置，将更多精力投入到外部合作和新兴技术领域。当时裁撤超过1000个岗位，约占员工总数的15%。今年1月，渤健的裁员范围扩大到研究部门。公司发言人表示，研究部门的新架构将匹配优先临床前项目的需求，并将资源转向外部机遇。面对核心产品专利悬崖和阿尔茨海默病药物Aduhelm的商业化挫折，这家麻省剑桥的生物技术巨头正在重塑研发管线。通过外部合作补充内部研发，重点布局神经科学领域的新型治疗模式。TONACEA02“走钢索”在专利悬崖阴影、研发难度攀升、成本高涨、医保支付压力大的困境下，大部分MNC都选择收缩战线、聚焦核心。比如，默沙东不断围绕K药做加法，对RNA、细胞治疗等领域投资较少；诺华在CGT、AI驱动靶点发现等方面持续大投入；阿斯利康直接砍掉CNS，继续加大肿瘤领域的投资力度，尤其是ADC。渤健则选择“走钢索”，在CNS领域不断加注。今年2月，渤健与Stoke Therapeutics就ASO疗法zorevunersen治疗特定遗传性癫痫达成合作。2024年10月，渤健与Neomorph达成14.5亿美元合作，共同开发治疗阿尔茨海默病等神经系统疾病的分子胶降解剂。同年8月，渤健与诺奖得主Craig Mello创立的Atalanta Therapeutics合作，针对亨廷顿病等CNS靶点开发RNAi疗法。2023年用73亿美元收购Reata，充实神经系统研发管线。虽然说，CNS拥有巨大的未满足需求，潜力无限，但有业内人士表示，这个领域五年内诞生重磅炸弹的概率相对其他领域更小。高风险是否会带来高利润，还不能下定论，但渤健的转型确实初见成效。2024年财报显示，渤健多发性硬化症业务收入43.50亿美元，同比下降7%；罕见病业务收入19.88亿美元，同比增加10%。今年第一季度继续延续上述势头，财报显示，针对罕见病、阿尔茨海默病和产后抑郁的新上市产品实现销售额翻倍，正在改变其商业化布局。渤健总裁兼首席执行官表示，第一季度业绩强劲，符合长期增长战略预期。商业产品组合的转型令人鼓舞，期内约45%的产品收入来自多发性硬化业务以外的重要药物。具体来看，第一季度总收入24.31亿美元，同比增长8%；产品收入17.27亿美元，同比增长3%。按业务划分，多发性硬化治疗产品收入同比下降10%至9.53亿美元，生物类似药收入同比缩减5%至1.81亿美元。罕见病业务同比增长36%，收入5.63亿美元；其中，用于治疗脊髓性肌萎缩症的Spinraza贡献了主要增量，销售额达到4.24亿美元。阿尔茨海默病药物Leqembi在全球销售额约9600万美元，保持稳步增长。渤健和卫材仍然在大力推进Leqembi的后续开发。今年1月，Leqembi静脉注射制剂（IV）在美国新增早期阿尔茨海默病适应症。渤健也正在申请Leqembi的皮下注射剂型用于维持治疗，预计审批日期为今年8月31日。如果获批，Leqembi将成为首款可通过自动注射器，在家进行皮下注射的阿尔茨海默病治疗药物，注射过程预计平均仅需15秒。此外，渤健还在进行Leqembi的III期临床试验，针对无症状阿尔茨海默病患者，预计2028年获得关键数据。其他阿尔茨海默病治疗药物的研发，如BIIB080已处在II期临床试验。同时，公司还在推进其他神经退行性疾病的研发，以进一步巩固其在CNS领域的地位，如针对帕金森病的BIIB122项目，目前处于II期临床阶段。TONACEA03CNS困局渤健的战略重组并非孤例，而将新的增长曲线寄希望于CNS的也不止渤健一家，这其中不乏百亿美元的资产迁移。2025年开年，强生豪掷146亿美元收购专注于CNS疾病治疗的Intra-Cellular Therapies公司，将其核心产品抗精神分裂症药物Caplyta收入囊中。在更早之前的2023年12月，BMS以140亿美元收购Karuna Therapeutics，获得70年来精神分裂症FIC新药Cobenfy（KarXT）。该产品已经于2024年9月获FDA批准上市，成为数十年来首个获FDA批准用于治疗精神分裂症的新作用机制药物。CNS的医疗需求和市场潜力毋庸置疑。数据显示，全球超过10亿人患有神经精神或神经退行性疾病——相当于每8人中就有1人受此困扰。仅强生收购的Caplyta，2023年销售额就达4.62亿美元，同比增长86%。强生预测这次收购获得的口服抗精神病产品Caplyta（lumateperone）销售峰值有望突破50亿美元。投资公司Jefferies也预计礼来的阿尔茨海默病新药Kisunla（Donanemab），在巅峰时期的年销售额接近30亿美元。然而，CNS药物的研发困境也显而易见。诺华以7.7亿美元收购Cadent Therapeutics获得的NMDAr变构调节剂管线，罗氏与Relay Therapeutics就SHP2变构抑制剂达成的合作相继败北。艾伯维87亿美元“打水漂”事件也足够让人在CNS领域犹豫一下——其收购Cerevel Therapeutics获得的M4选择性正向变构调节剂Emraclidine，未能在两项针对精神分裂症的II期研究中达到预期终点。去年10月，艾伯维又花费14亿美元收购Aliada，收获处于Ⅰ期临床的潜在BIC阿尔茨海默病疗法ALIA-1758。监管环境的日益严格，也促使MNC更加谨慎地对待研发项目。在CNS这个复杂领域，新药获批难度加大，使得MNC在权衡风险与收益时更加保守。不过，多种新型治疗模式有望重塑CNS药物研发格局。分子胶降解剂成为新宠。近两年该领域已产生超10笔交易，总金额超过百亿美元。2024年10月，诺华、渤健、辉瑞接连入场，一个月内达成三笔重磅合作。双抗药物在肿瘤领域大放异彩后，也开始向CNS扩展。4月，致力于开发用于免疫肿瘤学和神经退行性疾病的双特异性抗体技术公司ABL Bio，宣布与GSK达成协议，开发神经退行性疾病的新药。当传统药物形态难以突破CNS疾病治疗的瓶颈，核酸药物、蛋白降解剂等新一代治疗模式或将开启神经科学的新时代。参考文章：1、Biogen taps City Therapeutics in RNAi deal worth up to $1B；endpts2、强生放大招；同写意3、当阿斯利康向神经类药物说“再见”；新浪财经