$Regenxbio(RGNX)$
REGENXBIO计划与FDA合作，寻找前进路径，目标是重新提交BLA
ROCKVILLE, Md., Feb. 9, 2026 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec) for the treatment of Mucopolysaccharidosis II (MPS II), an ultra-rare neurodegenerative disease also known as Hunter syndrome.
马里兰州罗克维尔，2026年2月9日/PRNewswire/ -- REGENXBIO公司（纳斯达克股票代码：RGNX）今日宣布，美国食品药品监督管理局（FDA）已就其用于治疗黏多糖贮积症II型（MPS II，也称为亨特综合征）的RGX-121（clemidsogene lanparvovec）生物制品许可申请（BLA）发布了一份完整回应函（CRL）。这是一种超罕见的神经退行性疾病。
In May 2025, the FDA accepted the RGX-121 BLA under the accelerated approval pathway. In the February 7, 2026 CRL, the FDA stated that it had agreed to the study protocol in principle and outlined several reasons for not approving the gene therapy, including uncertainty regarding the study eligibility criteria to adequately define a population with neuronopathic disease (vs. attenuated disease), the comparability of the natural history external control to the study population, and the appropriateness of CSF HS D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. The CRL lists several potential paths forward, including a new study, treating additional patients and conducting longer-term follow up, and using an untreated control arm, all of which would be challenging in an ultra-rare disease population, like MPS II.
2025年5月，FDA接受了RGX-121 BLA的加速审批通道。在2026年2月7日的完整回应函中，FDA表示原则上同意研究方案，并列出了不批准该基因疗法的几个原因，包括对如何充分定义患有神经病变疾病（而非轻型疾病）人群的研究资格标准存在不确定性、自然史外部对照与研究人群之间的可比性问题，以及脑脊液HS D2S6作为预测临床效益的可能性较大的替代终点是否合适的问题。CRL列出了一些潜在的后续路径，包括进行一项新的研究、治疗更多患者并进行长期随访、使用未治疗的对照组，所有这些在像MPS II这样的超罕见病人群中都是具有挑战性的。
"This decision is devastating for the families of boys living with this progressive, life-threatening disease," said Curran Simpson, President and CEO of REGENXBIO. "We are concerned about FDA's feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease. We remain confident in the quality and volume of evidence demonstrating the long-term potential of RGX-121 to positively change the trajectory of Hunter syndrome. This program has been in development for over 10 years. We are incredibly grateful to all the patients, their families, investigators, and site staff who have supported this program and our continued efforts to bring a much-needed new treatment option to the Hunter syndrome community. We will continue those efforts."
“这一决定对那些患有这种渐进式的、危及生命的疾病的男孩家庭来说是一个毁灭性的打击。”REGENXBIO总裁兼首席执行官Curran Simpson表示，“我们对FDA关于整体开发路径和在评估数据背景下的反馈感到担忧，尤其是考虑到这一不可逆的超罕见疾病迫切的治疗需求。我们仍然对证明RGX-121长期潜力能够积极改变Hunter综合征进程的数量众多且高质量的证据充满信心。该项目已经开发了十多年。我们非常感谢所有支持该项目以及我们持续努力为Hunter综合征社区带来亟需的新治疗选择的患者、他们的家人、研究人员和现场工作人员。我们将继续努力。”
Throughout active discussions during the BLA process, REGENXBIO believed it had addressed the points raised in the CRL through the submission of additional data and responses to numerous information requests. Independent, leading global MPS and biomarker experts conducted analyses and reviews with the FDA, as well. Ultimately, the FDA did not agree the data set provided substantial evidence of effectiveness to support approval of RGX-121 for the treatment of MPS II.
在BLA审查过程中积极讨论期间，REGENXBIO认为它通过提交额外数据和回复大量信息请求解决了CRL中提出的问题。独立的全球领先的MPS和生物标志物专家也与FDA一起进行了分析和审查。最终，FDA并不认为提供的数据集提供了支持批准RGX-121治疗MPS II的有效性的实质性证据。
REGENXBIO plans to request a Type A meeting to discuss the CRL, as well as the planned BLA resubmission to provide additional evidence from global MPS II experts to further clarify the neuronopathic patient population and additional longer-term clinical data to support evidence of effectiveness. REGENXBIO intends to find a path forward as quickly as possible with the goal of resubmitting the BLA.
REGENXBIO计划请求召开A类会议，讨论CRL以及计划中的BLA重新提交事宜，以提供来自全球MPS II专家的额外证据，进一步明确神经病变患者群体，并提供额外的长期临床数据来支持有效性证据。REGENXBIO希望尽快找到一条前进路径，目标是重新提交BLA。
"MPS II is a very complex disease, but its impact is well established, resulting in irreversible brain damage for the majority of patients; without appropriate treatments stopping this neurocognitive decline, the neuronopathic MPS II child will die prematurely, usually in their mid-teens," said Joseph Muenzer, M.D., Ph.D., Director, Muenzer MPS Research and Treatment Center, Bryson Distinguished Professor in the Division of Genetics and Metabolism, Department of Pediatrics Genetics, University of North Carolina at Chapel Hill. "I remain encouraged by the clinical data behind RGX-121. New innovations like gene therapy could make a significant impact for these patients, and time is precious for these families."
“MPS II是一种非常复杂的疾病，但其影响已经被充分证实，大多数患者会出现不可逆的脑损伤；如果不采取适当的治疗阻止这种神经认知能力下降，患有神经病变的MPS II儿童通常会在十几岁时早逝。”Joseph Muenzer博士说道，他是Muenzer MPS研究与治疗中心主任，Bry杰出教授，北卡罗来纳大学教堂山分校儿科遗传学系遗传学与代谢科成员。“我依然受到RGX-121背后的临床数据鼓舞。像基因疗法这样的创新可能对这些患者产生重大影响，而时间对这些家庭来说非常宝贵。”
"I've seen the severe impact of MPS II on patients and their families firsthand and am extremely disheartened by today's news," said Terri Klein, President and CEO, National MPS Society. "Families know the devastating trajectory of this disease all too well and have waited 20 years for new treatment options. They cannot wait any longer. Drug development for ultra-rare disease must be streamlined to allow new medicines to reach patients. We urge the FDA to find a swift path forward so that boys living with MPS II and their families have the chance for a better life."
“我亲眼目睹了MPS II对患者及其家庭造成的严重影响，因此对今天的消息感到极度失望。”国家MPS协会主席兼首席执行官Terri Klein表示，“家属们深知这种疾病的毁灭性轨迹，并且已经等待了20年的新治疗选择。他们不能再等了。对于超罕见疾病的药物研发必须简化，以便让新药更快地到达患者手中。我们敦促FDA找到快速前进的方法，使那些患MPS II的男孩及其家庭有机会过上更好的生活。”
About RGX-121 (clemidsogene lanparvovec)
RGX-121 is a potential one-time gene therapy for the treatment of boys with MPS II, designed to deliver the iduronate-2-sulfatase (IDS) gene to the CNS. Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted iduronate-2-sulfatase (I2S) protein beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 expressed protein is structurally identical to normal I2S.
关于RGX-121（clemidsogene lanparvovec）
RGX-121是一种潜在的一次性基因疗法，用于治疗患有MPS II的男孩，旨在将艾杜糖醛酸-2-硫酸酯酶（IDS）基因递送到中枢神经系统（CNS）。在CNS内的细胞中递送IDS基因可以提供一个永久性的分泌型艾杜糖醛酸-2-硫酸酯酶（I2S）蛋白来源，超越血脑屏障，从而实现整个CNS细胞的长期交叉校正。RGX-121表达的蛋白质在结构上与正常I2S完全相同。
The BLA for RGX-121 for MPS II was supported by positive biomarker, functional and safety data from the CAMPSIITE I/II/III trial, including out to 12 months. RGX-121 has been well tolerated in all patients dosed across all phases of the CAMPSIITE trial.
CAMPSIITE I/II/III 试验的积极生物标志物、功能和安全性数据（最长至12个月）支持了RGX-121治疗MPS II的BLA申请。在CAMPSIITE试验的所有阶段中，所有接受治疗的患者对RGX-121的耐受性良好。
RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.
RGX-121已获得FDA授予的孤儿药产品、罕见儿科疾病、快速通道及再生医学高级治疗（RMAT）称号，并获得欧洲药品管理局的先进治疗药物产品（ATMP）分类。
About Mucopolysaccharidosis Type II (MPS II)
MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme I2S leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate CSF HS D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder.
关于黏多糖贮积症II型（MPS II）
MPS II（亨特综合症）是一种罕见的X连锁隐性疾病，由溶酶体酶I2S缺乏导致糖胺聚糖（GAGs）积累所致，其中包括组织中的硫酸肝素（HS），最终导致细胞、组织和器官功能障碍，包括中枢神经系统（CNS）。在疾病的严重形式下，早期发育里程碑可能得以达成，但在18至24个月时发育迟缓显而易见。针对MPS II神经学表现的具体治疗方法仍然是重要的未满足医疗需求。MPS II患者的I2S酶活性的关键生物标志物包括其底物CSF HS D2S6，已被证明与该疾病的神经认知表现相关。
ABOUT REGENXBIO Inc.
REGENXBIO is a biotechnology company on a mission to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the field of AAV gene therapy. REGENXBIO is advancing a late-stage pipeline of one-time treatments for rare and retinal diseases, including RGX-202 for the treatment of Duchenne; clemidsogene lanparvovec (RGX-121) for the treatment of MPS II and RGX-111 for the treatment of MPS I, both in partnership with Nippon Shinyaku; and surabgene lomparvovec (ABBV-RGX-314) for the treatment of wet AMD and diabetic retinopathy, in collaboration with AbbVie. Thousands of patients have been treated with REGENXBIO's AAV platform, including those receiving Novartis' ZOLGENSMA. REGENXBIO's investigational gene therapies have the potential to change the way healthcare is delivered for millions of people. For more information, please visit .
关于REGENXBIO公司
REGENXBIO是一家生物技术公司，致力于通过基因疗法的治愈潜力改善生活。自2009年成立以来，REGENXBIO一直是AAV基因疗法领域的先驱。REGENXBIO正在推进一系列针对罕见病和视网膜疾病的晚期一次性治疗管线，包括用于治疗杜氏肌营养不良症的RGX-202；与日本新药株式会社合作开发的clemidsogene lanparvovec (RGX-121)用于治疗MPS II和RGX-111用于治疗MPS I；以及与艾伯维公司合作开发的surabgene lomparvovec (A