A Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome, Comprising a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Period Followed by an Open-Label Treatment Period

开始日期2025-06-10

申办/合作机构

ACADIA Pharmaceuticals, Inc.

NCT04988867

/ Terminated临床2/3期

An Open-Label Study of Trofinetide for the Treatment of Girls Two to Five Years of Age Who Have Rett Syndrome

To investigate the safety and tolerability of long-term treatment with oral trofinetide in girls with Rett syndrome

开始日期2021-09-22

申办/合作机构

ACADIA Pharmaceuticals, Inc.

NCT04776746

/ Terminated临床3期

An Open-Label Extension Study of Continuing Treatment With Trofinetide for Rett Syndrome

To investigate the safety and tolerability of continued long-term treatment with oral trofinetide in girls and women with Rett syndrome

开始日期2020-11-08

申办/合作机构

ACADIA Pharmaceuticals, Inc.

100 项与曲非奈肽相关的临床结果

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100 项与曲非奈肽相关的转化医学

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100 项与曲非奈肽相关的专利（医药）

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项与曲非奈肽相关的文献（医药）

2026-06-01·BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis and evaluation of trofinetide prodrug based on diketopiperazine strategy

Article

作者: Bian, Jing ; Feng, Jun ; Lu, Jianguang ; Guo, Chen ; Xu, Zhiru ; Dong, Yuanzhen ; Feng, Xue ; Luo, Tao ; Peng, Wenjing

Trofinetide is the only drug approved worldwide for the treatment of Rett syndrome, a rare pediatric disease. However, its extremely short half-life, large oral dose, high incidence of gastrointestinal adverse reactions, and consequently high treatment costs pose formidable clinical and economic challenges. To address these issues, we employed a diketopiperazine strategy to design a novel class of trofinetide prodrugs, aiming to alter the administration route and optimize its pharmacokinetic properties. Through the determination of solubility and in vitro conversion half-life, and based on the established screening criteria, TFD 10 was selected from the series of qualified compounds as a representative for pharmacokinetic evaluation. TFD 10 exhibited efficient conversion to trofinetide both in vitro and in vivo. Compared to oral administration of trofinetide, subcutaneous injection of TFD 10 markedly prolonged the half-life (6-fold) and substantially increased systemic exposure (40-fold), successfully achieving the design objectives. This study validates the feasibility of this strategy, and TFD 10, as a proof-of-concept lead compound, demonstrates significant potential for further development.

2026-04-01·ADVANCES IN THERAPY

A Phase 1, Randomized, Open-Label Study to Assess the Bioequivalence of Trofinetide as a Ready-to-Use Oral Solution and Constituted Powder for Oral Solution in Healthy Adults

Article

作者: Pathak, Sanjeev ; Yamamoto, Amy ; Darwish, Mona ; Youakim, James M ; Adegbenle, Yvonne ; Tejwani, Ravi ; Nunez-Disla, Rene ; Chen, Yonghua

INTRODUCTION:

Trofinetide is an approved treatment in the USA and Canada for Rett syndrome in patients aged ≥ 2 years. Trofinetide is currently supplied as a ready-to-use oral solution (TOS). A new trofinetide powder for oral solution (TPOS) offers potential advantages: smaller configuration of unit-dose packs; excludes preservatives, synthetic red dye, and maltitol; can be dissolved in a range of volumes in cold/room temperature water or water-based beverages; does not require refrigeration. To ensure that the formulation change does not impact trofinetide pharmacokinetics, a bioequivalence study assessed trofinetide pharmacokinetics after single 12,000-mg oral trofinetide doses administered as TOS and TPOS and the impact of a reduced constitution volume on trofinetide bioavailability.

METHODS:

In this randomized, open-label, three-period, three-treatment design study, 38 healthy adults each received one 12,000-mg trofinetide dose of TOS (60 mL [200 mg/mL]; treatment A), TPOS constituted in 60 mL of water (200 mg/mL; treatment B), and TPOS constituted in 25 mL of water (480 mg/mL; treatment C) in sequence ABC or BAC. Bioequivalence for each treatment comparison was confirmed if the 90% confidence interval (CI) of the geometric mean ratio (GMR) for the maximum observed drug concentration (C_max), area under the concentration-time curve from time 0 to time t (AUC_0-t), and AUC from time 0 to infinity (AUC_0-∞) fell within 80-125%.

RESULTS:

The criteria for bioequivalence were met for AUC_0-t (GMR 99.62%; CI 96.52-102.83), AUC_0-∞ (GMR 99.50%; CI 96.44-102.66), and C_max (GMR 99.52%; CI 94.99-104.27) between treatment B and treatment A. All other treatment comparisons (C vs A and B vs C) also met the bioequivalence criteria. The most frequent treatment-emergent adverse event was diarrhea (n = 6 [15.8%]). No serious or unexpected adverse events occurred during the study.

CONCLUSION:

The bioequivalence demonstrated in this study supports the clinical interchangeability of TPOS and TOS and shows that TPOS can be constituted using adjustable volumes of water without affecting bioavailability. There were no unexpected adverse events reported with trofinetide when administered as TPOS and TOS.

2026-03-04·Science Translational Medicine

Modulating alternative splicing of MECP2 is a potential therapeutic strategy for Rett syndrome

Article

作者: Anderson, Ashley G. ; Liu, Zhandong ; Bajikar, Sameer S. ; Chen, Hu ; Bajic, Aleksandar ; Tirumala, Harini P. ; Wang, Wei ; Kim, Jean J. ; Li, Yan ; Zoghbi, Huda Y. ; Trostle, Alexander J. ; Zahabiyon, Mahla ; Wang, Li

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl-CpG–binding protein 2 ( MECP2 ), which encodes a transcriptional regulator essential for maintenance of normal neuronal function. The current US Food and Drug Administration–approved treatment for RTT, trofinetide, mildly alleviates some symptoms. In contrast, reintroducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique to e2 ), leading to production of only e1 mRNA, and showed that this up-regulated MeCP2 by 50 to 60% in mice. Next, we investigated the consequences of isoform switching in two independent RTT induced pluripotent stem cell (iPSC)–derived neuron models harboring mutations that reduce both MeCP2 expression and function. Exon 2 deletion in neurons derived from patients with MeCP2-G118E up-regulated MeCP2, ameliorated morphological and electrophysiological changes, and corrected the dysregulated transcriptome in these neurons. Isoform switching in neurons derived from patients with MeCP2-G118E, modeling a severe RTT mutation, only modestly affected MeCP2 protein abundance and, despite this, led to a partial transcriptomic rescue. Last, an exon 2–skipping morpholino up-regulated MeCP2-E1 in vivo in mice. These data set the stage for a potential therapeutic strategy using antisense oligonucleotides to promote isoform switching in patients with RTT who carry partially functioning alleles of MECP2 .

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项与曲非奈肽相关的新闻（医药）

2026-06-16

·BioSpace

JW Pharmaceutical Presents Preclinical Results and Global Development Strategy for DDC-02, a Novel Therapeutic Candidate for Rare Neurodevelopmental Disorders

Data presented at WODC USA 2026 Support Potential Application Across Multiple Indications, Including Pitt-Hopkins Syndrome, Fragile X Syndrome, and Rett Syndrome Restoration of Cognitive and Behavioral Function to Normal Levels Observed in Adult Disease Models Global Clinical Development Planned with Pitt-Hopkins Syndrome as the Lead Indication SEOUL, South Korea--(BUSINESS WIRE)-- #Biotech -- JW Pharmaceutical (KRX:001060) presented preclinical findings and its global development strategy for DDC-02, a therapeutic candidate for rare neurodevelopmental disorders, at the World Orphan Drug Congress USA 2026 (WODC USA 2026) in Boston, Massachusetts, from June 9 to 11. The presentation featured data demonstrating the effects of DDC-02 across animal models of several rare neurodevelopmental disorders, including Pitt-Hopkins syndrome (PTHS), Fragile X syndrome (FXS), and Rett syndrome (RTT), each of which arises from distinct genetic causes. Across these models, DDC-02 consistently restored deficits in cognitive and behavioral function. DDC-02 is an orally administered small-molecule candidate discovered by JW Pharmaceutical. The compound has been shown to modulate intracellular signaling pathways involved in neurodevelopment and neural circuit function. In preclinical studies, DDC-02 restored impaired cognitive and behavioral performance to levels comparable to those observed in healthy control animals across models of PTHS, FXS, and RTT. These findings suggest that DDC-02 may improve cognitive and behavioral function by modulating synaptic plasticity and neural circuit activity. Taken together, the data indicate DDC-02’s potential applicability across multiple rare neurodevelopmental disorders sharing common deficits in cognition and behavior, despite their distinct genetic origins. Noteworthy was the observation that cognitive and behavioral function was restored to normal levels even in animals with well-established disease phenotypes. Neurodevelopmental disorders are generally believed to be difficult to reverse once symptoms have become established, as they arise from abnormalities occurring during early stages of brain development. The ability of DDC-02 to restore function in these models suggests that meaningful recovery may be achievable even after disease manifestations have emerged, highlighting the potential for functional restoration within mature neural circuits. JW Pharmaceutical is evaluating Pitt-Hopkins syndrome as the lead indication for DDC-02 and is targeting entry into global multi-regional clinical studies in 2028. It plans to subsequently expand development into additional rare neurodevelopmental disorders, including Fragile X syndrome and Rett syndrome. The company also outlined its global development and partnering strategy during WODC USA 2026. Throughout the conference, JW Pharmaceutical held business development meetings with pharmaceutical companies, biotechnology firms, and investment groups to explore a range of collaboration opportunities, including co-development partnerships and licensing transactions. Dr. Sun Young Kim, Executive Head of R&D Strategy at JW Pharmaceutical said, “DDC-02 has demonstrated consistent efficacy across neurodevelopmental disorder models with distinct genetic etiologies,” adding “The observation that cognitive and behavioral function was restored to normal levels even in adult disease models is encouraging. We believe these findings support the potential of DDC-02 as a novel therapeutic approach for patients with rare neurodevelopmental disorders.” He added, “We expect to advance DDC-02 through global clinical development and strategic partnerships to bring a meaningful new treatment option to patients and families affected by these conditions.” About Pitt-Hopkins Syndrome (PTHS) PTHS is an ultra-rare neurodevelopmental disorder caused by loss-of-function mutations in the TCF4 (Transcription Factor 4) gene. The condition is characterized by severe intellectual disability, profound speech impairment, autism-like features, breathing abnormalities, and epilepsy. Its prevalence is estimated at approximately one in 30,000-40,000 individuals. There are currently no approved disease-modifying therapies, and treatment is primarily focused on symptom management and supportive care. About Fragile X Syndrome (FXS) FXS is an inherited neurodevelopmental disorder caused by mutations in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene and is the most common inherited cause of intellectual disability. Clinical manifestations include learning disabilities, cognitive impairment, autism spectrum-related features, anxiety, and hyperactivity. The disorder affects approximately one in 4,000 males and one in 8,000 females. No disease-modifying therapies have been approved to date. The global FXS treatment market was estimated at approximately USD 1.2–2.6 billion in 2024, with continued growth anticipated as multiple investigational therapies advance through clinical development. About Rett Syndrome (RTT) Rett syndrome is a rare neurodevelopmental disorder primarily caused by mutations in the MECP2 (Methyl-CpG Binding Protein 2) gene and predominantly affects females. Patients typically experience apparently normal early development followed by progressive loss of language and motor skills, repetitive hand movements, gait abnormalities, and seizures. The disorder affects approximately one in 10,000–15,000 individuals worldwide. In 2023, the U.S. Food and Drug Administration approved trofinetide (Daybue®), the first therapy specifically indicated for Rett syndrome. Annual treatment costs are estimated at approximately USD 375,000 per patient, underscoring the significant unmet medical need and the substantial value attributed to effective therapies in this field. Contacts JW Pharmaceutical Jeong-jae Yoo Head of PR, Corporate Communications jw_pr@jw-group.co.kr

2026-06-08

·BioSpace

Marvel Biosciences Receives Notice of Allowance for Australian Patent Application Covering Composition of Matter for its Lead Therapeutic Candidate MB-204

CALGARY, Alberta, June 08, 2026 (GLOBE NEWSWIRE) -- Marvel Biosciences Corp. (TSXV: MRVL | OTC: MBCOF ), and its wholly owned subsidiary, Marvel Biotechnology Inc. (collectively the “Company” or “Marvel”), a drug discovery company developing novel, therapeutics for autism spectrum disorder and related conditions is pleased to announce that the Australian patent application 2021235803 covering MB-204 was accepted on May 7, 2026. The patent is expected to be granted shortly after August 28, 2026. The Australian notice of allowance further strengthens Marvel's global composition-of-matter patent portfolio for MB-204, reinforcing the Company's intellectual property position as it advances into Phase I clinical development following positive preclinical efficacy and toxicology results. Such includes recent preclinical studies in Rett syndrome models that demonstrated that MB-204 significantly outperformed the approved therapy trofinetide across multiple efficacy endpoints and produced sustained therapeutic benefits that persisted after treatment cessation, suggesting the potential for disease-modifying effects. Broadening patent protection across key pharmaceutical markets enhances the asset's commercial value by extending market exclusivity, reducing competitive risk, and increasing its attractiveness for potential licensing, partnering, and strategic investment opportunities. “We are continuing to extend our composition of matter patent protection of MB-204 to all major markets”, commented Marvel CEO Rod Matheson “and we continue to look forward to receiving similar rulings for the other jurisdictions. We have also recently filed for patents on a novel liquid-based formulation of MB-204 which should help lengthen the lifetime of our patent estate.” MB-204 is a novel fluorinated analogue of the approved adenosine A2a receptor antagonist Istradefylline which is used for the treatment of Parkinson’s Disease. MB-204 has demonstrated superior pharmacokinetics and completed pre-clinical toxicology testing and has shown excellent pre-clinical efficacy studies in depression and multiple models of autism including Rett Syndrome. The compound is currently being tested in Fragile X models. Currently, around 1 in 36 children at age 8 have been diagnosed with autism spectrum disorder which underscores the urgency for new agents. The patent advancement follows a series of significant achievements in 2026, including the granting of U.S. and Japanese composition-of-matter patents for MB-204, the selection of Novotech as the Company's contract research organization for its planned Phase I clinical trial, the securing of non-dilutive funding support from Alberta Innovates, strategic investment participation from 5 Horizons Ventures, and the development of novel pediatric-friendly liquid formulations that may further expand the Company's intellectual property estate. Collectively, these achievements continue to validate Marvel's scientific platform, strengthen its credibility within the biotechnology sector, and support the Company's transition from a pre-clinical organization to a clinical-stage drug development company. About Marvel Biosciences Corp. Marvel Biosciences Corp., through its wholly owned subsidiary Marvel Biotechnology Inc., is a Calgary-based biotechnology company developing new treatments for neurological diseases and neurodevelopmental disorders. Our lead drug candidate, MB-204, is a novel fluorinated derivative version of Istradefylline, an approved Parkinson’s drug and the only adenosine A2A receptor blocker currently on the market. Research shows that blocking the A2A receptor may help treat conditions such as autism, depression, and Alzheimer’s disease. Marvel is also exploring MB-204’s potential in rare disorders like Rett syndrome and Fragile X syndrome, aiming to bring new options to patients with few effective treatments. Contact Information: Marvel Biosciences Corp. J. Roderick (Rod) Matheson, Chief Executive Officer Email: rod@marvelbiosciences.com Dr. Mark Williams, President and Chief Science Officer Email: mark@marvelbiosciences.com Tel: 403 770 2469 Website: | Twitter/X | LinkedIn Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is deﬁned in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this press release. All information contained in this news release with respect to the Company and its subsidiary,(collectively, the "Parties") were supplied by Marvel, respectively, for inclusion herein and each parties' directors and oﬃcers have relied on each other for any information concerning such Party. This news release may contain forward-looking statements and other statements that are not historical facts. Forward-looking statements are often identiﬁed by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact, included in this release, including, without limitation, statements regarding the future plans and objectives of the Company are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could diﬀer materially from those anticipated in such statements. Important factors that could cause actual results to diﬀer materially from the expectations of the Company and include other risks detailed from time to time in the ﬁlings made by the Company under securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to diﬀer materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. As a result, the Company cannot guarantee that the above events on the terms will occur and within the time disclosed herein or at all. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may diﬀer materially from those anticipated. Forward-looking statements contained in this news release are expressly qualiﬁed by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by Canadian securities law.

临床1期

2026-06-05

·雪球

Neurogene：EXACT平台赋能的全长MECP2基因疗法能否成为Rett综合征的Best-in-Class？

$Neurogene(NGNE)$摘要NeurogeneInc.（纳斯达克代码：NGNE）是一家专注于罕见神经系统疾病基因疗法的临床阶段生物技术公司。公司核心资产NGN-401是一款用于治疗Rett综合征的AAV9基因疗法，目前正在进行关键性注册临床试验Embolden™，已完成全部20名患者的入组，约90%的患者已完成给药，预计2026年第二季度完成给药，2026年中期公布所有10名受试者12个月以上的全部数据。公司的核心技术平台EXACT™（ExpressionAttenuationviaConstructTuning）是一种基于microRNA的转基因调控技术，旨在将蛋白表达量控制在安全有效的“治疗窗口”内，是公司区别于同赛道竞争者的关键差异化优势。Rett综合征在美国、欧盟和英国的女性患者总数约为15000-20000人，全球尚无获批的疾病修正疗法，市场空缺巨大。NGN-401已获得FDA突破性疗法认定、RMAT认定及EMAPRIME认定等多个加速审评资质。在竞争格局方面，目前最直接的竞争对手是TayshaGeneTherapies的TSHA-102，后者采用迷你型MECP2基因并结合miRARE调控技术，已于2026年4月获得FDA突破性疗法认定。两者构成了一对一的竞争态势。公司财务状况稳健：截至2026年3月31日，现金及短期投资余额约为2.432亿美元，预计可支撑运营至2028年第一季度。一、公司概览1.1公司定位与使命Neurogene成立于2018年，是一家临床阶段的生物技术公司，致力于为罕见神经系统疾病开发基因药物。公司的核心理念是“生物学优先设计”（Biology-firstdesign），从疾病生物学出发，结合精准递送技术和EXACT平台来构建产品管线。1.2发展里程碑公司成立以来取得了一系列关键进展：2020年与爱丁堡大学达成EXACT技术合作；2021年完成B轮融资并推进NGN-401进入临床前研究；2023年首位Rett综合征患者完成给药；2024年公布早期临床数据；2025年启动注册临床试验并自建cGMP工厂完成临床级载体生产；2026年2月获得FDA突破性疗法认定。1.3近期关键里程碑（2026年度）完成Embolden注册临床试验全部患者的给药：预计2026年第二季度完成公布Phase1/2试验完整12个月以上数据：计划2026年中期公布全部10名受试者的更新数据启动PPQ（工艺性能确认）活动：计划2026年中期启动二、技术平台详解：EXACT™2.1背景：传统基因疗法的“剂量难题”传统基因疗法面临的核心挑战在于无法精确控制外源基因的最终表达水平。表达过低则无效，表达过高则产生毒性。对于MECP2这类对基因剂量极度敏感的基因，这一问题尤为突出——即使是微量的过表达也可能导致神经系统毒性，这被称为“过表达毒性”（overexpressiontoxicity）。2.2EXACT™的工作原理EXACT全称ExpressionAttenuationviaConstructTuning，是一种基于microRNA的反馈调节回路。其核心机制如下：1.载体递送：利用AAV9作为载体，将带有EXACT调节元件的全长MECP2基因递送至靶细胞2.蛋白生产与实时检测：细胞开始生产MeCP2蛋白，EXACT系统同时实时监测蛋白产量3.反馈调节：当蛋白产量超过预设阈值时，EXACT系统通过其内置的microRNA机制精准消除多余的信使RNA（mRNA），自动将蛋白产量拉回安全有效的范围内这种“智能恒温器”式的设计使得EXACT平台能够在单个细胞的水平上实现自我调节，而非依赖于宏观的剂量调控，这是其与传统基因疗法的本质区别。三、候选管线3.1核心产品：NGN-401（Rett综合征）NGN-401是公司管线中的核心资产，也是目前临床进展最快的候选药物。关键设计参数：转基因：全长MECP2基因递送载体：AAV9血清型给药方式：脑室内注射（ICV）剂量水平：1×10¹⁵vg（每次一次性给药）递送后免疫抑制方案：类固醇单药方案ICV给药方式的优势：临床前模型数据显示，ICV比鞘内腰椎注射（IT-L）更能实现对脑部和神经系统关键区域的广泛靶向。美国每年约有30000例ICV手术由神经外科医生执行，手术成熟且恢复期短。3.2Rett综合征：疾病与市场概况疾病病因：Rett综合征是由X染色体上的MECP2基因变异所致，导致功能性MeCP2蛋白缺乏。MeCP2是一种对大脑和神经系统正常发育至关重要的DNA结合蛋白。发病过程：患儿在6-18个月期间出现发育迟缓，随后失去已获得的能力（如语言、手部功能），在大约3岁时进入发育停滞期。核心症状：表达性和接受性交流能力丧失有目的的手部功能丧失，伴随刻板手部动作步态异常和行动障碍癫痫、呼吸节律异常、严重便秘流行病学与市场规模：目前尚无获批的疾病修正疗法，现有治疗仅限于症状管理。支付方对功能性改善高度重视，且Rett综合征数十年的生存期支持高价、持久的基因疗法获得医保覆盖。3.3NGN-401临床试验结果详解（1）Phase1/2临床试验设计与患者基线这是一项开放标签、多中心临床试验，共10名女性Rett综合征患者接受1×10¹⁵vg剂量的NGN-401一次性给药。患者位于疾病严重程度谱系的全范围——从“中度”到“极重度”均有覆盖。（2）临床有效性结果截至2025年10月30日数据截止日，NGN-401展现出以下效果：核心成果汇总：100%的患者在核心疾病领域（精细运动/手部功能、粗大运动/行动、交流）均表现出功能性改善累计获得35项发育里程碑持续时间长：最长达24个月持续获得新技能，未见平台期88%的患者获得临床总体印象改善评分（CGI-I）改善多领域能力积累使得患者能够完成日益复杂的日常活动，提升独立性和健康相关生活质量各领域的具体改善描述：按随访时点的发育里程碑累计情况：患者在治疗后随时间推移持续积累多领域发育里程碑，且未见增速放缓，表明NGN-401可能实现真正的病程修饰效果。（3）安全性与耐受性截至数据截止日，1×10¹⁵vg剂量在10名患者中显示出良好的总体耐受性：治疗相关不良事件（TEAEs）：10名患者中9例有TEAEs，但全部为Grade1（轻度）或Grade2（中度）级别。多数为AAV疗法已知的潜在风险，且已缓解或在缓解中严重不良事件（SAEs）：共报告3例与研究药物无关的SAEs，1例治疗相关的SAEs（Grade2，与神经传导检测异常相关，现已恢复正常范围）无HLH（噬血细胞性淋巴组织细胞增生症）病例报告无ICV手术相关不良事件无提示MeCP2过表达的症状或体征癫痫控制良好3.4Embolden™注册临床试验设计Embolden是NGN-401用于支持BLA（生物制剂许可申请）申请的关键性注册临床试验，其核心设计获得FDA的认可。试验设计概述：试验类型：单臂、基线对照、开放标签患者数量：20名Rett综合征女性患者年龄要求：≥3岁给药方案：一次性脑室内注射1×10¹⁵vg主要观察期：12个月临床试验中心：全美13个Rett综合征卓越中心（RettCentersofExcellence）有效性终点：主要终点：12个月时基于反应者的复合终点，定义为——CGI-I评分≤3（即“有改善”），以及至少获得1项发育里程碑的改善成功率标准：≥35%的反应率（即20名患者中至少7名达到上述指标）关键次要终点：CGI-I评分≤2（即“显著改善”）至少获得2项发育里程碑的改善发育里程碑清单：28项预先指定的发育里程碑来自自然历史数据库，已获得FDA、关键意见领袖（KOLs）和照护者一致认可，涵盖三大功能领域：精细运动/手部功能（8项）：伸手拿玩具、独立从杯子喝水、指状抓取、钳状抓取、手指进食、传递物体、独立使用餐具粗大运动/行动（12项）：有支撑坐起、无支撑坐立、站立扶握、独立行走、上下楼梯、短跑10英尺等交流能力（8项）：对名字/词语有反应、遵从指令、指物表达需求、挥手拜拜、咿呀学语、使用有意义的词语和短语Embolden的关键风险化解因素：Phase1/2试验的数据已证实多个关键设计要素被成功带入注册试验，有助于降低Embolden的失败风险：Phase1/2试验中的反应率已超过Embolden主要终点设定的成功率标准，提供了显著的统计学确定性相同的1×10¹⁵vg剂量从Phase1/2延续至Embolden统一的类固醇单药免疫抑制方案全美Rett综合征卓越中心牵头执行集中化、盲态中心审阅的标准化视频里程碑评估流程四、竞争格局分析4.1Rett综合征治疗领域概览据DelveInsight报告，目前有超过20家制药公司和20余种管线药物在Rett综合征领域开展研究，涵盖基因疗法、小分子药物等多种治疗模式。主要的非基因疗法竞争者包括：AnavexLifeSciences（Blarcamesine）：小分子σ-1受体激动剂，已完成Phase3试验，但主要终点未达到统计学显著性（审评存在争议）BiomedIndustries（Bionetide）：在2026年3月启动Phase3试验NeurenPharmaceuticals/Acadia（NNZ-2566，trofinetide）：于2023年获得FDA批准（Daybue™），是Rett综合征领域首个获批的药物，但仅能对症控制症状，并非疾病修饰疗法，需每日两次口服，且有显著胃肠道不良事件4.2基因疗法赛道：NGN-401vs.TSHA-102在基因疗法领域，目前直接竞争的只有Neurogene（NGN-401）和TayshaGeneTherapies（TSHA-102）两家公司。Taysha的TSHA-102已于2026年4月获得FDA突破性疗法认定，竞争格局已进入“双雄并立”阶段。4.3竞争格局的关键观察1.递送方式的差异可能决定疗效上限NGN-401采用ICV给药，旨在实现更广泛的全脑和神经系统靶向分布。临床前数据显示，ICV相对于IT-L（鞘内腰椎注射）覆盖了更全面的Rett综合征病理生理相关脑区。然而，ICV手术的侵入性和操作复杂性可能影响部分临床中心的采纳意愿和医保支付的路径。2.全长基因vs.迷你基因NGN-401递送全长MECP2基因，理论上能够实现MeCP2蛋白的全部生物学功能。Taysha采用迷你基因（“mini-MECP2”）策略，虽然从分子尺寸上可能有利于包装和递送效率，但其蛋白功能的完整性始终是需要回答的关键科学问题。3.FDA加速路径对标两家公司的注册试验均已获得FDA支持。Taysha在2026年4月获批突破性疗法认定后，整体进展快速追赶Neurogene。然而值得关注的是，Neurogene的全长基因选择使其在生物学合理性方面具有潜在优势，但这需要通过更多临床数据来证实。从商业化和监管角度看，Neurogene的完整临床数据包完整性更加充分——NGN-401已积累了长达24个月的临床数据，且Embolden的单一关键试验可能支持更简化的BLA审评流程。Taysha则通过两项分开进行的试验（REVEAL+ASPIRE）来获得不同年龄段群体的数据。五、财务状况分析5.1最新财务数据（截至2026年第一季度）Neurogene在2026年5月12日公布了2026年第一季度财务数据：净亏损：3,090万美元（2025年第一季度为2,260万美元）研发费用（R&D）：2,520万美元，高于2025年同期的1,780万美元现金、现金等价物和短期投资余额：截至2026年3月31日为2.432亿美元5.22025财年全年财务数据5.3现金跑道分析截至2025年12月31日，公司持有约2.690亿美元现金，预计足以覆盖运营支出至2028年第一季度。基于2025年约7,800万美元的年度现金消耗率，公司拥有约3.4年的现金跑道。2026年第一季度末的现金余额降至2.432亿美元，主要反映了临床试验进度推进导致的研发支出增加。六、风险因素6.1临床开发风险临床试验失败：Embolden注册试验虽然已入组全部20名患者，但仍在评估中，最终数据可能与中期结果不符FDA监管路径不确定性：虽然公司已就单一关键试验方案获得FDA一致性认可，但监管要求和审评标准仍可能在最终BLA审评阶段发生变化罕见病临床终点设计的挑战：28项发育里程碑的定义与标准化视频评估流程虽然已获得FDA认可，但在实施中仍然存在主观判断的区间6.2竞争风险Taysha的快速追赶：TSHA-102已获得突破性疗法认定并积极推进注册试验，竞争窗口正在收窄已上市的Daybue™（trofinetide）：虽然是症状管理药物，但已占据部分临床医生的处方惯性，未来NGN-401上市后将面临产品定位和市场教育的挑战七、核心催化剂追踪（2026下半年）八、估值逻辑概述1.巨大的未满足临床需求：Rett综合征全球尚无根治方法，患者生命周期长（数十年的持续照护和医疗消耗），有效治疗方案存在强劲定价能力2.技术平台差异化优势明显：EXACT平台解决了全长MECP2基因过表达毒性的核心难题，是Neurogene区别于行业竞争者的技术护城河3.真实临床数据展现潜力：Phase1/2试验中100%患者在多个领域获得功能改善，最长数据可达24个月，且无严重安全隐患4.监管路径加速明显：获得FDA突破性疗法认定、RMAT认定、EMAPRIME及英国MHRA创新通行证等多种加速通道5.稳健的现金基础：2.432亿美元现金支撑到2028年第一季度，能够覆盖核心催化剂节点（数据发布→BLA提交）

100 项与曲非奈肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	曲非奈肽	-	DB06045

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
Rett综合征	美国	ACADIA Pharmaceuticals, Inc.	2023-03-10

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑震荡	临床2期	美国	Neuren Pharmaceuticals Ltd.	2014-09-01
脆性X综合征	临床2期	美国	Neuren Pharmaceuticals Ltd.	2014-01-01
创伤性脑损伤	临床1期	澳大利亚	Neuren Pharmaceuticals Ltd.	2010-03-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04988867 (DAFFODIL, Pubmed \| Med)	临床2/3期	Rett综合征	-	Trofinetide	糧醖鬱憲鏇鏇膚醖淵選(膚構壓廠築齋壓範壓蓋) = 80.0% 網艱鹽鏇淵鑰鹽顧範餘 (鏇醖築醖顧壓醖獵範網 ) 更多	积极	2025-06-01
NCT04776746 (LILAC-2, CTgov)	临床3期	Rett综合征	77	Trofinetide	襯選鏇衊願構鑰窪製壓 = 蓋網獵鑰觸鑰製願顧憲選構鬱齋構壓壓鏇鬱醖 (繭願範窪願糧鑰齋膚範, 鬱獵鬱顧範膚蓋遞網繭 ~ 鏇鹽鹽窪窪獵鬱鏇鏇鬱) 更多	-	2024-09-27
NCT04988867 (DAFFODIL \| DAFFODIL™, CTgov)	临床2/3期	Rett综合征	15	Trofinetide	憲遞選鏇願遞鬱蓋艱築 = 鏇觸衊製顧壓選網觸製憲糧繭鏇鹹獵齋繭淵淵 (鏇廠襯觸蓋鏇獵網獵繭, 窪糧繭積製夢簾鹹廠鑰 ~ 簾蓋夢選顧餘範窪遞廠) 更多	-	2024-09-24
NCT04776746 (LILAC-2, BusinessWire) 人工标引	N/A	Rett综合征	-	DAYBUE (LILAC-1)	膚蓋積憲構齋願淵顧糧(範鑰餘憲窪觸衊鏇願構) = 顧鬱衊糧齋憲齋網願網網選遞製顧構鬱鏇餘範 (願蓋夢鬱簾顧構壓鹹鬱, 1.62) 更多	积极	2024-07-18
NCT04776746 (LILAC-2, BusinessWire) 人工标引	N/A	Rett综合征	-	Placebo (LILAC-1)	膚蓋積憲構齋願淵顧糧(範鑰餘憲窪觸衊鏇願構) = 憲遞鹹壓鹽廠鑰齋餘襯網選遞製顧構鬱鏇餘範 (願蓋夢鬱簾顧構壓鹹鬱, 1.61) 更多	积极	2024-07-18
NCT04776746 (LILAC-2, Pubmed)	临床3期	Rett综合征	77	Trofinetide	範壓膚廠簾製構範憲觸(積簾顧製獵遞艱憲簾鹽) = 27.3% 憲蓋衊齋簾淵蓋鬱鹹選 (觸鬱憲襯壓範蓋繭糧壓 ) 更多	积极	2024-07-16
AAN2024 人工标引	N/A	Rett综合征	325	Trofinetide	醖鏇築淵醖窪襯廠積壓(衊鬱壓壓壓夢網艱膚觸) = 齋網襯齋蓋遞網獵鹽網齋積築築願膚艱築獵築 (壓構願衊遞構鏇膚淵顧 )	积极	2024-04-13
NCT04279314 (LILAC™, CTgov)	临床3期	Rett综合征	154	Trofinetide	簾窪窪膚網願願選夢壓 = 淵窪鏇窪範範製鏇艱壓鹽餘願壓積蓋齋構壓積 (積膚夢網襯衊構襯簾鹹, 衊蓋觸製淵膚選淵鏇觸 ~ 製齋襯憲膚網構鏇壓齋) 更多	-	2024-04-11
S37.008 (AAN2024)	临床3期	Rett综合征	33	Trofinetide (LILAC/LILAC-2)	鏇鑰憲蓋憲願襯網選簾(夢築襯淵窪壓鏇積構製) = 壓蓋構鑰鬱廠壓鹽獵鹹襯網鹽觸遞顧簾廠襯選 (餘壓顧觸夢窪夢齋醖鏇 ) 更多	积极	2024-04-09
NCT04181723 (LAVENDER, CTgov)	临床3期	Rett综合征	187	Trofinetide (Drug - Trofinetide)	醖願衊簾醖壓製獵醖簾(築網積醖製艱網齋鏇夢) = 鬱衊範餘構齋衊製選範網選鏇願鏇糧淵淵壓糧 (繭鑰壓壓觸製鹹鏇膚簾, 0.94) 更多	-	2024-04-08
NCT04181723 (LAVENDER, CTgov)	临床3期	Rett综合征	187	Placebo (Placebo)	醖願衊簾醖壓製獵醖簾(築網積醖製艱網齋鏇夢) = 築鏇齋膚衊糧壓糧築憲網選鏇願鏇糧淵淵壓糧 (繭鑰壓壓觸製鹹鏇膚簾, 0.90) 更多	-	2024-04-08
LAVENDER study (AAN2023)	临床3期	Rett综合征	-	Trofinetide	製顧窪衊遞衊壓壓遞構(憲鑰願網糧廠衊壓壓憲): P-Value = 0.0257 更多	积极	2023-04-25
LAVENDER study (AAN2023)	临床3期	Rett综合征	-	Placebo	製顧窪衊遞衊壓壓遞構(憲鑰願網糧廠衊壓壓憲): P-Value = 0.0257 更多	积极	2023-04-25