Idursulfase

Rolling submission of BLA initiated for tividenofusp alfa; preparations ongoing for potential U.S. commercial launch in late 2025 or early 2026Alignment through recent interactions with CDER on path to accelerated approval and conversion to full approval for tividenofusp alfaProductive collaboration continues under START for an accelerated development and approval path for DNL126 SOUTH SAN FRANCISCO, Calif., April 02, 2025 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (NASDAQ: DNLI), today announced that the company’s initiation of a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for the treatment of Hunter syndrome (MPS II) has been received by the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA). Denali continues to have regular, collaborative, and productive engagement with CDER and is aligned with CDER on the content of the BLA data package, including the use of cerebrospinal fluid heparan sulfate (CSF HS) as a surrogate endpoint to support an accelerated approval, as well as the full approval conversion path. Denali expects to complete the BLA submission in the first half of May 2025 and continues to prepare for a potential commercial launch in the U.S. in late 2025 or early 2026. “We are grateful to the FDA for their ongoing support of our BLA filing and continued dedication to advance new medicines,” said Carole Ho, M.D., Chief Medical Officer of Denali. “This regulatory milestone brings us closer to our goal of delivering a new treatment option to the Hunter syndrome community as we continue to listen, learn, and seek their advice in bringing tividenofusp alfa to patients. Our progress has broader positive implications supporting the expansion of our Enzyme TransportVehicle franchise of next-generation enzyme replacement therapies to treat the brain and body. In this context, we appreciate the ongoing and productive collaboration with CDER through the START program as we align on an accelerated development and approval path for DNL126 for the potential treatment of Sanfilippo syndrome.” About Hunter Syndrome (MPS II)Hunter syndrome (MPS II) is a rare genetic disease that affects over 2,000 individuals worldwide, primarily males, and leads to physical, cognitive, and behavioral symptoms. Hunter syndrome is caused by mutations in the iduronate-2-sulfatase (IDS) gene, which leads to a deficiency of the IDS enzyme. Symptoms often begin emerging around age two and include physical complications, including organ dysfunction, joint stiffness, hearing loss and impaired growth, and neurocognitive symptoms with impaired development. The disease is characterized by a buildup of glycosaminoglycans (GAGs) in lysosomes — the part of the cell that breaks down materials including GAGs. The current standard of care, enzyme replacement therapy, partially treats physical symptoms but does not cross the blood-brain barrier, and as a result, cognitive and behavioral symptoms experienced by the majority of patients with Hunter syndrome are not addressed. Therapies that address the range of cognitive, behavioral, and physical manifestations of the disease are recognized as an unmet need for this patient community.1 About Tividenofusp AlfaTividenofusp alfa (or DNL310) is composed of the iduronate 2-sulfatase (IDS) enzyme fused to Denali’s proprietary Enzyme TransportVehicle™ (ETV), uniquely designed to deliver IDS into the brain and the body, with the goal of addressing behavioral, cognitive, and physical symptoms of Hunter syndrome (MPS II). The U.S. Food and Drug Administration has granted Fast Track and Breakthrough Therapy designations to tividenofusp alfa for development in the treatment of Hunter syndrome (MPS II). The European Medicines Agency has granted Priority Medicines designation to tividenofusp alfa. The Phase 2/3 COMPASS study is enrolling participants with MPS II in North America, South America, and Europe to support global approval. Participants are randomized 2:1 to receive either tividenofusp alfa or idursulfase, respectively. More information about the COMPASS study can be found here. Tividenofusp alfa is an investigational therapeutic and has not been approved for use by any Health Authority. About Sanfilippo Syndrome Type A (MPS IIIA)MPS III, also called Sanfilippo syndrome, is a rare, genetic lysosomal storage disease that causes neurodegeneration. There are four main types of MPS III, depending on the enzyme affected. Type A is caused by genetic defects that result in reduction in the activity of N-sulfoglucosamine sulfohydrolase (SGSH), an enzyme responsible for degrading heparan sulfate in the lysosome. There are no approved treatments for MPS IIIA. About DNL126 (ETV:SGSH)DNL126 (ETV:SGSH) is an intravenously administered, Enzyme TransportVehicle™ (ETV)-enabled SGSH replacement therapy designed to cross the BBB via receptor-mediated transcytosis into the brain and to enable broad delivery of SGSH into cells and tissues throughout the body with the goal of addressing the behavioral, cognitive, and physical manifestations of MPS IIIA. DNL126 is an investigational therapeutic and has not been approved for use by any Health Authority. About the Phase 1/2 study of DNL126Denali is conducting a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory clinical efficacy of DNL126 in participants with MPS IIIA. The core study period is approximately 6 months and is followed by an open-label extension for approximately 18 months. More information about the Phase 1/2 study can be found here. About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier for neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the blood-brain barrier and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding plans, timelines, and expectations related to Denali's Enzyme TransportVehicle™ (TV) platform and its therapeutic and commercial potential; plans, timelines, and expectations relating to tividenofusp alfa (DNL310), including enrollment in the ongoing global Phase 2/3 COMPASS study, the timing of completion of its BLA submission, the likelihood of accelerated and full approval, and the timing and likelihood of commercial launch; expectations for ongoing communications with the FDA; plans, timelines, and expectations related to DNL126, including enrollment in and timing of the Phase 1/2 study; and statements made by Denali’s Chief Medical Officer. Actual results may differ materially from those expressed or implied by these forward-looking statements due to a variety of risks and uncertainties. These include, but are not limited to: risks arising from adverse economic conditions and their impact on Denali’s business and operations; the possibility of events or changes that could lead to the termination of Denali’s collaboration agreements; challenges associated with Denali’s transition to a late-stage clinical drug development company; the ability of Denali and its collaborators to complete the development and, if approved, the commercialization of product candidates; difficulties in patient enrollment for ongoing and future clinical trials; reliance on third-party manufacturers and suppliers for clinical trial materials; dependence on the successful development of Denali’s blood-brain barrier platform technology and related programs; potential delays or failures in meeting expected clinical trial timelines; the risk that promising preclinical profiles may not be replicated in clinical settings; discrepancies between preclinical, early-stage, or preliminary clinical results and outcomes from later-stage trials; the occurrence of significant adverse events or other undesirable side effects; and the uncertainty surrounding regulatory approvals required for commercialization; Denali’s ability to advance a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2025 and Denali’s future reports to be filed with the SEC. Denali's product candidates are investigational, and their safety and efficacy profiles have not yet been established. No Denali product candidates have been approved by any health authority for any use. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Denali’s expectations, except as required by law. Reference Muenzer, J., et al. Community consensus for Heparan sulfate as a biomarker to support accelerated approval in Neuronopathic Mucopolysaccharidoses. Mol Genet Metab. 2024 Aug;142(4):108535 Investor ContactLaura Hansen, Ph.D.Vice President, Investor Relations(650) 452-2747hansen@dnli.comMedia ContactRich AllanFGS Global(503) 851-0807rich.allan@fgsglobal.com

1月27日，国家医保局发布《国家医疗保障局办公室关于印发<按病种付费医疗保障经办管理规程（2025版）>的通知》（以下简称《规程》），标志着DRG/DIP 新规正式落地实施，对于药企与医院而言，这是一场关乎 “价值医疗” 的大考，从药品研发生产到医疗服务提供，将迎来前所未有的挑战与机遇。药企和医院都需要在新的规则下重新审视自己的定位与发展策略，以适应精准医疗时代的到来。 图片来源：国家医保局 01. DRG/DIP2.0版：从“粗放分组”到“精准狙击” DRG/DIP 2.0版的升级绝非简单迭代，而是对医疗资源消耗的“精准制导”。相较1.0版本，2.0版主要通过精细化分组、数据标准化、配套机制完善三大核心变革，推动医保支付从“粗放控费”转向“精准价值医疗”。其核心逻辑事通过“数据透明化+支付刚性化”，终结“开药越多赚越多”的生态，倒逼行业淘汰低效产能、拥抱创新，最终实现患者、医院、医保三方利益的动态平衡。 《规程》明确，完善“1+3+N”多层次医疗保障体系下的按病种付费经办管理，加强按病种付费与医疗服务价格改革、集中带量采购、医保目录谈判、商业健康保险、基金监管等工作的协同。做好与即时结算、直接结算、同步结算的协同推进。加强与公立医院高质量发展、紧密型县域医共体建设、推动检查检验互认等医改工作的协调联动。 对于药企而言，传统的 “以量换价” 模式逐渐失效，单纯的药品销售数量增长不再等同于利润增长。相反，药企需要更加注重药品的临床价值和成本效益，研发出更具针对性和疗效的药品，以满足精准医疗的需求。同时，药企还需要加强与医疗机构的合作，通过提供优质的药品和服务，提升自身的竞争力。 对于医院来说，DRG/DIP 2.0 版的实施促使医院更加注重医疗质量和成本控制。医院需要优化诊疗流程，提高医疗服务的效率和质量，减少不必要的医疗资源浪费。与此同时，医院还需要加强信息化建设，提高数据的准确性和完整性，为 DRG/DIP 2.0 版的实施提供有力支持。 02.医保“组合拳”重构利益分配 随着DRG/DIP 2.0版的全面推开，破解医保、医院和患者“三方博弈”刻不容缓。对此，国家医保局和地方医保局推出了一系列配套政策： 提高医保数据公开力度，稳定医保政策预期 2025年1月23日，国家医保局办公室发布《关于建立医保数据工作组更好赋能医疗机构发展的通知》，要求确保各统筹地区医保数据工作组全面覆盖，定期向定点医药机构亮医保基金家底。数据内容包括医保基金收支、预算执行、DRG/DIP付费、结算清算进度等。DRG/DIP 支付方式数据包括：医保结算清单上传率、质控通过率，结算人次占比、特例单议申请和审核通过病例数量，及其占出院病例数比例等指标。 推进医保“三结算”，缓解医院资金压力 2025 年全国医疗保障工作会议上，提出推动医保与定点医药机构即时结算，与医药企业直接结算，在保障安全的前提下，探索商保、慈善互助等与基本医保同步结算（简称“三结算”）。去年，国家医保局发起督导各地拖欠医保款的“清欠”行动，2025年1月，印发了《关于推进基本医保基金即时结算改革的通知》，提出2025年全国80%左右统筹地区基本实现基本医保基金与定点医药机构即时结算，2026实现即时结算全覆盖。 探索医保办主任“双重管理”，强化内部监督 近期，浙江省印发《健全医院医保办协议管理机制省级试点方案》，浙江湖州的市、区县级医院的医保办主任不再由医院直接任命，而是由医院提名后，同级卫健部门会同医保部门共同聘任。这种“双重管理”机制可以在组织制度上打通医保局与医院的治理堵点，充分发挥医院医保处（科）在医保合规审核、经营管理咨询、患者医保服务方面的枢纽地位，让医保处（科）成为医保政策落地“最后一公里”的助推器，“三医”协同治理的缓冲阀。 DRG/DIP 2.0版的推进绝非孤军奋战，数据公开解决“规则可信度”，三结算解决“资金流动性”，双重管理解决“执行穿透力”，本质上是在医疗支付改革的“深水区”搭建新的治理框架——用透明度换信任，用效率换生存空间，用制衡换合规。当医保支付改革从“技术迭代”迈向“治理变革”，整个医疗产业链的生存法则也悄然转变：过去靠信息不对称赚钱的玩家将加速出清，而真正具备临床价值创造能力的主体将获得制度性红利。 03.暗战升级：谁在布局下一个医药黄金赛道？ DRG/DIP1.0支付体系的病组权重主要依据历史医疗费用数据确定，未充分考虑创新医疗技术费用。这导致患者接受新技术治疗时，实际费用可能超出支付标准。为控制成本，医疗机构可能减少创新药品、设备及治疗方案的使用，进而抑制新技术的应用。2024年6月，国务院办公厅印发《深化医药卫生体制改革2024年重点工作任务》中明确提出研究对创新药和先进医疗技术应用给予DRG/DIP付费中除外支付等政策倾斜。 国际上在DRG付费下创新医疗技术支付机制的探索已取得一定成果，如美国的新技术附加支付项目（NTAP）、德国的新诊断与治疗方法支付项目（NUB）以及法国的附加清单制度。这些机制为创新技术的合理支付提供了经验。相比之下，国内DRG/DIP付费下的创新医疗技术支付仍处于推进阶段。但是从推进DRG/DIP 2.0的本质不难看出，“用疗效定价”将驱动药企从“拼关系”转向“拼价值”。 临床价值足够“硬”的创新药，依旧可以在高权重病种中分得蛋糕。以有着“卷王”品种之称的PD-1药物为例，在特瑞普利单抗（10个适应症）小细胞肺癌（ES-SCLC）适应症纳入国家医保后，单周期自费治疗费用约 700 元，以每月一个治疗周期计算，年治疗费用约为8400元（700元/周期 × 12周期）。若考虑70%的医保报销比例，实际患者自付费用更低。然而该药物使用人次数的大幅提升，依然能够带动人均费用增长，实现院端市场放量。 图1:特瑞普利单抗国内医院销售量趋势 数据来源：PDB药物综合数据库-国内院端放大数据（涵盖中国24个省市自治区的公立二三级医院），中国医药工业信息中心 通过真实世界数据（RWD）撬动支付溢价是另一条路径。例如，2017年，苏州大学附属第一医院对治疗慢性髓性白血病（CML）的靶向药物格列卫（甲磺酸伊马替尼）和达希纳（尼洛替尼）开展了基于真实世界数据的研究。结果显示，靶向治疗虽增加了平均医疗支出，但显著降低了社会总成本（包括患者和看护者的劳动力损失）。基于此，这两款药被纳入医保支付范围，印证了数据即话语权：谁能用本土化证据证明疗效，谁就能在支付谈判中占据主动。 图2: 格列卫和达希纳国内医院销售量趋势 数据来源：PDB药物综合数据库-国内院端放大数据（涵盖中国24个省市自治区的公立二三级医院），中国医药工业信息中心 更有企业选择“绕道超车”。例如，北海康成聚焦罕见病领域，其国内获批上市产品海芮思（一种重组人酶替代疗法，用于治疗亨特综合征），在海芮思获批前，患者主要依赖进口药物Elaprase，其年治疗费用极高，平均每位患者每年花费约56万美元。网传海芮思药品售价高达225万（实际销售效果还需进一步观察），虽然该药受众狭窄，但高值罕见病药可以避开医保红海，同时，商保和自费市场为罕见病药物提供了新的支付渠道和市场空间，具有一定的蓝海潜力，尽管该部分仍需要政策支持和市场创新来进一步完善支付机制。 04.总结 DRG/DIP 2.0如同一台精密运行的筛分机，对于缺乏真实临床价值的产品，即便侥幸上市，也难以逃过支付标准的严格筛选，“伪创新”终将被无情地剥离，这促使企业重新审视自身产品的价值与定位。与此同时，那些能够在市场波动和变革中穿越周期的幸存者，早已将“价值医疗”刻入基因，通过持续研发投入和创新实践，不断提升产品的临床价值和成本效益，在DRG/DIP 2.0的支付体系下，它们将凭借卓越的临床价值和市场竞争力获得更多发展机遇。 这场变革的终极启示是：在支付改革的洪流中，唯有创造不可替代的价值，才能成为新时代的“适者”。 END 如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001