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更新于：2025-09-24
Golodirsen
更新于：2025-09-24
概要
基本信息
药物类型 ASO |
别名 Golodirsen (USAN/INN)、EXON-53 PMO、NG-12-0163 + [3] |
作用方式 调节剂 |
作用机制 DMD exon 53调节剂(DMD 外显子53调节剂) |
在研适应症 |
非在研适应症- |
非在研机构- |
权益机构- |
最高研发阶段批准上市 |
首次获批日期 美国 (2019-12-12), |
最高研发阶段(中国)- |
特殊审评快速通道 (美国)、加速批准 (美国)、孤儿药 (美国) |
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结构/序列
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Sequence Code 29924125
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关联
7
项与 Golodirsen 相关的临床试验CTRI/2022/09/045929
A Double-Blind, Placebo-Controlled, Multicenter Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy - ESSENCE
开始日期2022-10-05 |
申办/合作机构 |
NCT04708314
An Open-Label Study to Evaluate the Safety of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
This is an open-label study to evaluate the safety and tolerability of golodirsen injection in Non-ambulant DMD patients with confirmed genetic mutations amenable to treatment by exon 53 skipping (Golodirsen).
Golodirsen 30 mg/kg will be administered as an intravenous (IV) infusion over approximately 35 to 60 minutes once a week during the treatment period (up to 96 weeks). After the treatment period, patients can go into a safety extension period (not to exceed 48 weeks) until the patient is able to transition to commercially available drug or a separate golodirsen study.
Safety will be regularly assessed throughout the study via the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations. Exploratory assessments, including pulmonary function tests (PFTs), upper extremity testing, and other measurements of functional status, will occur at functional assessment visits every 12 weeks over the first year of treatment and approximately every 24 weeks over the second year of treatment.
Golodirsen 30 mg/kg will be administered as an intravenous (IV) infusion over approximately 35 to 60 minutes once a week during the treatment period (up to 96 weeks). After the treatment period, patients can go into a safety extension period (not to exceed 48 weeks) until the patient is able to transition to commercially available drug or a separate golodirsen study.
Safety will be regularly assessed throughout the study via the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations. Exploratory assessments, including pulmonary function tests (PFTs), upper extremity testing, and other measurements of functional status, will occur at functional assessment visits every 12 weeks over the first year of treatment and approximately every 24 weeks over the second year of treatment.
开始日期2020-10-31 |
申办/合作机构 |
NCT04179409
A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 in Subjects With DuchenneMuscular Dystrophy Carrying Eligible DMD Duplications.
This is an 48-week open-label study to determine the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 for the treatment of boys with duchenne muscular dystrophy who have a single exon duplication of either exon 45, 51 or 53, respectively. There will be weekly infusions and two muscle biopsies at baseline and at month 12.
开始日期2020-02-18 |
申办/合作机构 |
100 项与 Golodirsen 相关的临床结果
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100 项与 Golodirsen 相关的转化医学
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100 项与 Golodirsen 相关的专利（医药）
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40
项与 Golodirsen 相关的文献（医药）2025-08-01·Journal of Comparative Effectiveness Research
Real-world phosphorodiamidate morpholino oligomer treatment patterns in Duchenne muscular dystrophy: a claims-based analysis.
Article
作者: Veerapandiyan, Aravindhan ; Ung, Brian ; Signorovitch, James ; Nadkar, Aalok ; DeYoung, Kathryn ; Grabich, Shannon
Aim: Phosphorodiamidate morpholino oligomers (PMOs) are exon-skipping therapies administered through once-weekly intravenous infusions used to treat Duchenne muscular dystrophy (DMD). This study assessed treatment patterns among patients with DMD receiving PMOs using administrative claims data while accounting for limitations in claims data for these therapies. Materials & methods: This study used Inovalon® public and private closed claims data (1 June 2016-31 March 2024). Male patients with ≥1 claim for a PMO approved for DMD in the US (eteplirsen, casimersen, golodirsen and viltolarsen) were included. Index date was the first PMO claim. All available follow-up data were used to assess continuous PMO claims coverage, ≥60-day and ≥30-day gaps in PMO claims and PMO re-initiation after a gap. Adherence during 1 year after index was measured using proportion of days covered (PDC). Treatment patterns were also assessed in patients stratified by baseline algorithm-defined nonambulatory status (inferred from claims). Results: Among 397 patients included, median (IQR) follow-up time was 788 (484, 1109) days. Gaps in PMO claims coverage occurred in 190 (47.9%) and 254 (64.0%) patients using ≥60-day and ≥30-day gaps, respectively, among whom 110 (57.9%) and 176 (69.3%) had PMO re-initiation. Using ≥60-day and ≥30-day gap lengths, median (IQR) time to first gap in PMO claims was 25.5 (22.3, 32.9) months and 13.5 (10.2, 17.7) months, respectively and median (IQR) time to PMO re-initiation (not including gap time) was 4.4 (2.8, 8.7) months and 2.5 (1.7, 3.2) months. Median (IQR) PDC was 78.8% (38.8, 94.0) during 1 year after index. PMO treatment patterns were generally similar in patients stratified by algorithm-defined nonambulatory status. Conclusion: In an analysis of administrative claims data, adherence to PMO treatment for DMD was high. For patients with a gap in PMO claims, most subsequently re-initiated treatment, indicating lower discontinuation rates than previously reported.
2025-07-29·MUSCLE & NERVE
Patient With Duchenne Muscular Dystrophy Who Tolerated Viltolarsen After Prior Anaphylaxis to Golodirsen.
Letter
作者: Bassell-Hawkins, Julia ; Piccoli, Cara ; Rocha, Carolina Tesi
2025-06-01·MOLECULAR THERAPY
Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases
Review
作者: Muntoni, Francesco ; Zhou, Haiyan ; Aguti, Sara ; Torres-Masjoan, Laia
Four exon-skipping antisense oligonucleotides (ASOs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD), including eteplirsen, golodirsen, viltolarsen, and casimersen. Current data from long-term real-world usage of these ASOs suggests a broad safety profile and a delay in muscle deterioration. Nevertheless, the exon-skipping efficacy and dystrophin protein production of these ASOs are limited, suggesting the need for more efficient ASOs. Over the past decade, many studies have focused on improving ASO efficacy by incorporating novel chemical modifications or bioconjugations of a variety of moieties including peptides or antibodies to increase their cellular uptake by muscle cells, their endosomal escape, and their nuclear import to boost therapeutic efficacy. Many of these newly developed exon-skipping ASOs have been studied in clinical trials in DMD patients, and early findings suggest clear improvements in molecular efficacy compared to the earlier version of ASOs, although the safety track record may not be the same as the first-generation compounds. Here, we summarize the recent preclinical and clinical developments of ASOs and discuss the future challenges of exon-skipping therapies for DMD and other neuromuscular diseases.
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项与 Golodirsen 相关的新闻（医药）2025-09-23
▲体内CAR疗法-全球研究与发展格局（2025）免费领取！ 摘要：基因治疗作为医学创新的前沿领域，为遗传性疾病和复杂疾病的治疗带来了革命性希望。然而，未受调控的治疗基因表达可能引发免疫排斥、器官毒性等并发症，制约其临床应用。本文系统梳理了当前基因调控技术的发展现状，涵盖外源转基因表达调控、内源性基因调控、基因调控网络干预及递送系统优化四大核心方向，解析了组织特异性启动子、诱导系统、RNA 编辑、表观遗传编辑等关键技术的原理与应用场景，并探讨了当前面临的递送效率、脱靶效应、临床转化等挑战。这些技术的突破，正推动基因治疗从 “单一治疗” 向 “精准调控” 升级，为罕见遗传病乃至癌症、神经退行性疾病等复杂病症提供新的治疗路径。
一、基因治疗的现状：从 “有药可用” 到 “精准可控”
基因治疗已从早期的理论探索迈入临床应用阶段，截至 2024 年底，全球已有多款基因与细胞治疗产品获批，覆盖遗传性视网膜病变、白血病、脊髓性肌萎缩症（SMA）等曾经 “无药可治” 的疾病。例如，2017 年获批的Luxturna是首个美国 FDA 批准的基因治疗产品，通过腺相关病毒（AAV） 载体向视网膜细胞递送 RPE65 基因，治愈了遗传性视网膜营养不良；同年，CAR-T 细胞疗法开启个性化免疫治疗时代，首款产品 Kymriah 获批用于治疗 B 细胞白血病，至今已有 7 款 CAR-T 产品获 FDA 批准。
不过，临床实践暴露了基因治疗的核心难题 ——基因表达失控。以血友病治疗为例，2022 年获批的 Roctavian（治疗血友病 A）虽通过 AAV5 载体递送凝血因子 Ⅷ 基因，但部分患者出现内质网（ER）应激：由于凝血因子 Ⅷ 在细胞内易错误折叠形成类淀粉结构，堆积在内质网中引发细胞损伤，导致治疗效果随时间下降。此外，AAV 载体的随机整合风险也不容忽视，动物实验发现，AAV 可能整合到肝脏细胞基因组的特定位点（如小鼠 Rian 基因座），导致附近微 RNA 或逆转座子过度表达，增加肝癌风险。
这些问题推动基因治疗的核心需求从 “实现基因递送” 转向 “精准调控基因表达”。当前研究聚焦三大目标：一是让治疗基因只在特定组织或细胞中表达（细胞类型特异性）；二是让基因表达强度和时间可按需调节（动态可控性）；三是减少对正常细胞的干扰（低脱靶效应）。二、外源转基因调控：给治疗基因装 “智能开关”
外源转基因是基因治疗的核心工具，但如何让其 “该表达时表达，该停时停”，是技术突破的关键。目前主要通过启动子调控、小分子诱导、microRNA（miRNA）调控三大策略实现精准控制。（一）组织特异性启动子：让基因 “认对地方”
不同组织细胞拥有独特的基因表达模式，组织特异性启动子正是利用这一特性，让治疗基因只在目标组织中 “启动”。早期研究多直接采用天然启动子，如红细胞中的 γ- 珠蛋白启动子、心肌细胞中的肌球蛋白轻链启动子，但天然启动子存在活性低、特异性不足的问题。
如今，科学家通过 “元件组合” 优化启动子性能。例如，在杜氏肌营养不良症（DMD）治疗中，研究人员将肌肉肌酸激酶（MCK）核心启动子与 E-box 增强子元件结合，并替换较弱的天然 E-box 为强活性版本，构建出的人工启动子在肌肉细胞中的表达活性提升数倍，且不会在肝脏、心脏等非目标器官中 “误启动”。更先进的技术还结合了高通量筛选与机器学习：通过大规模平行报告实验（MPRA）同时检测数千个增强子的活性，再利用算法设计出完全人工合成的启动子，这类启动子不仅特异性更高，还能适配病毒载体的包装容量限制。（二）小分子诱导系统：给基因装 “遥控开关”
对于需要根据病情调整表达强度的场景，小分子诱导系统成为关键工具。这类系统通过外源添加小分子药物，触发治疗基因的 “开启” 或 “关闭”，如同给基因装了 “遥控开关”。
最经典的是四环素诱导系统：早期的 “Tet-off” 系统中，四环素会抑制转录因子结合，从而关闭基因表达；后续优化的 “Tet-on” 系统则反过来，只有添加多西环素（四环素衍生物），才能激活基因表达，该系统已用于调控 CAR-T 细胞中 CAR 蛋白的表达，减少 “脱靶攻击” 正常细胞的风险。另一类小分子诱导二聚化系统则通过药物诱导蛋白质相互作用来调控基因，例如基于植物激素脱落酸（ABA）的系统，将转录激活因子拆分为两个片段，分别与 ABA 结合蛋白 PYL1 和 ABI 融合，只有添加 ABA，两个片段才会结合形成完整激活因子，启动基因表达，该系统已用于调控内源性基因的转录。
此外，诱导性蛋白降解系统可直接控制治疗蛋白的 “寿命”。以生长素诱导降解子（AID） 为例，将生长素结合蛋白 IAA17 与治疗蛋白融合，添加生长素后，融合蛋白会被细胞内的 TIR1 蛋白识别并通过泛素 - 蛋白酶体途径降解，实现治疗蛋白的快速清除。这类系统在 CAR-T 治疗中可作为 “安全开关”，若出现严重毒副作用，添加小分子即可降解 CAR 蛋白，终止治疗。（三）miRNA 调控：给基因加 “负反馈刹车”
miRNA是细胞内天然的 “基因沉默分子”，通过结合 mRNA 的特定序列抑制基因表达。科研人员利用这一特性，设计出miRNA 响应性表达盒，让治疗基因避开非目标细胞，或避免表达过量。
在肢带型肌营养不良症 2A 的治疗中，治疗基因钙蛋白酶 3（calpain3）在骨骼肌中具有治疗作用，但在心脏中表达会引发毒性。研究人员在钙蛋白酶 3 基因的 mRNA 中插入心脏特异性 miR-208a 的结合位点：当基因意外进入心脏细胞时，miR-208a 会结合到 mRNA 上抑制其翻译，而在骨骼肌中，由于 miR-208a 不表达，基因可正常发挥作用。此外，miRNA 还可构建 “负反馈循环”：在 Rett 综合征治疗中，治疗基因 MeCP2 过量表达会导致神经毒性，研究人员将受 MeCP2 调控的 miRNA 序列与 MeCP2 基因串联，当 MeCP2 表达过高时，miRNA 也会随之增多，反过来抑制 MeCP2 的 mRNA 翻译，实现 “自我调节”。
图 1 外源转基因的三大调控方式（A）启动子调控：天然启动子利用细胞自身特异性，人工启动子通过组合增强子元件提升活性，诱导型启动子则需外源小分子触发表达；（B）蛋白质水平调控：AID 系统通过生长素诱导蛋白降解，利妥昔单抗诱导的 Caspase-9 系统可触发细胞凋亡，作为 CAR-T 的安全开关；（C）miRNA 调控：利用细胞特异性 miRNA 抑制非目标细胞中的基因表达，或构建负反馈循环控制表达强度。三、内源性基因调控：编辑 “自身基因” 解难题
除了调控外源导入的治疗基因，直接干预细胞内源性基因的表达，能更精准地修复遗传缺陷或纠正病理状态。当前主要通过反义寡核苷酸、表观遗传编辑、RNA 编辑、靶向蛋白降解四大技术实现。（一）反义寡核苷酸：“修正” 错误的基因产物
反义寡核苷酸（ASO）是一类短链核酸分子，通过与 mRNA 结合，调控其剪切或降解，从而修正错误的基因产物。在杜氏肌营养不良症（DMD）治疗中，患者的 dystrophin 基因常因外显子突变导致阅读框移位，无法合成正常蛋白。ASO 可结合到突变外显子的剪切位点，诱导细胞在转录时 “跳过” 突变外显子，生成缩短但仍有功能的 dystrophin 蛋白，目前已有 Exondys 51、Vyondys 53 等多款 ASO 药物获批。
在脊髓性肌萎缩症（SMA）治疗中，ASO 则展现出 “重编程” 剪切的能力：患者的 SMN1 基因缺失，但 SMN2 基因（与 SMN1 高度同源）因一个碱基差异，转录时易跳过第 7 外显子，生成无功能蛋白。ASO 可结合 SMN2 mRNA 的特定区域，促进第 7 外显子的 inclusion，让 SMN2 合成有功能的 SMN 蛋白，替代 SMN1 的作用，这款名为 Spinraza 的 ASO 药物已成为 SMA 的一线治疗方案。（二）表观遗传编辑：不改变基因序列的 “精准调控”
表观遗传修饰是细胞调控基因表达的天然机制，包括 DNA 甲基化、组蛋白修饰、染色质结构变化等，这些修饰不改变基因序列，但能长期影响基因 “开关” 状态。表观遗传编辑技术通过 CRISPR 等工具，将表观遗传修饰酶（如甲基转移酶、乙酰转移酶）靶向递送至特定基因位点，实现基因表达的 “精准调控”，且避免了 DNA 切割可能引发的脱靶效应。
例如，在脆性 X 综合征中，患者的 FMR1 基因因启动子区域CGG 重复序列扩增导致甲基化水平升高，基因被沉默。研究人员利用dCas9（失活的 Cas9） 融合 DNA 去甲基化酶 TET1，靶向 FMR1 启动子区域，去除过度的甲基化修饰，重新激活 FMR1 基因表达。在动物实验中，该方法可恢复神经细胞中 FMR1 蛋白的水平，改善认知缺陷。此外，表观遗传编辑还可用于 “关闭” 有害基因，如通过 dCas9 融合组蛋白去乙酰化酶（HDAC），降低肝癌细胞中 MYC 癌基因的表达，抑制肿瘤生长。（三）RNA 编辑：“修正” mRNA 上的错误碱基
RNA 编辑直接对 mRNA 进行碱基修饰，无需改变基因组序列，安全性更高，尤其适用于单碱基突变导致的遗传病。目前应用最广泛的是腺苷脱氨酶（ADAR）介导的 A-to-I 编辑：ADAR 可将 mRNA 中的腺苷（A）转化为肌苷（I），细胞翻译时会将 I 识别为鸟苷（G），从而修正 A→G 的突变。
科研人员将 dCas13（失活的 Cas13，可结合 RNA 而非 DNA）与 ADAR 融合，构建出 “RNA 编辑工具”：dCas13 通过向导 RNA（sgRNA）靶向突变的 mRNA 位点，ADAR 则对该位点的 A 进行脱氨编辑。例如，在早衰症治疗中，患者的 LMNA 基因存在 G→A 突变，导致核纤层蛋白异常；利用该工具可将 mRNA 中的 A 编辑为 I（即 G），恢复正常蛋白合成。更先进的策略还能利用细胞内天然的 ADAR：设计 “向导 RNA” 与目标 mRNA 结合形成双链 RNA，触发内源性 ADAR 对突变位点进行编辑，无需导入外源酶，降低免疫排斥风险，目前该技术已进入临床实验阶段。（四）靶向蛋白降解：直接清除 “致病蛋白”
对于因蛋白功能异常（如突变蛋白聚集）导致的疾病，靶向蛋白降解（TPD） 技术可直接清除致病蛋白，弥补传统小分子药物 “只能抑制、不能清除” 的缺陷。这类技术的核心是蛋白水解靶向嵌合体（PROTAC）：PROTAC 分子由两部分组成，一端结合致病蛋白，另一端结合细胞内的泛素连接酶，通过 “桥梁作用” 让致病蛋白被泛素标记，进而被蛋白酶体降解。
例如，在多发性骨髓瘤治疗中，来那度胺等免疫调节药物本质就是一类 PROTAC，可结合 Ikaros（IKZF1）和 Aiolos（IKZF3）蛋白，将其递送至 CRL4 泛素连接酶，促进降解，从而抑制肿瘤细胞生长。除了小分子 PROTAC，还可通过基因治疗递送 “生物型降解剂”，如融合抗体与泛素连接酶的融合蛋白，实现对细胞膜表面致病蛋白（如 PD-L1）的特异性降解，目前这类技术已在癌症免疫治疗中开展研究。
图2 内源性基因的调控策略（A）表观遗传编辑：CRISPRi（dCas9 融合抑制效应子）通过增加异染色质、促进 DNA 甲基化抑制基因表达；CRISPRa（dCas9 融合激活效应子）通过打开染色质、促进组蛋白乙酰化激活基因；（B）RNA 调控：siRNA 通过 RISC 复合体降解目标 mRNA，Cas13 可通过切割、编辑或甲基化调控 RNA，还可介导 RNA 反式剪接修正突变；（C）蛋白降解：PROTAC、分子胶等工具通过泛素 - 蛋白酶体途径降解致病蛋白，溶酶体靶向嵌合体则引导蛋白进入溶酶体降解。四、基因调控网络：从 “单个基因” 到 “系统干预”
复杂疾病（如癌症、神经退行性疾病）往往不是单个基因异常导致的，而是整个基因调控网络（GRN） 失衡的结果。因此，干预基因调控网络、重塑细胞功能，成为基因治疗的新方向。（一）转录因子：调控网络的 “总开关”
转录因子（TF） 是基因调控网络的核心元件，一个转录因子可调控数百个下游基因，通过调控转录因子实现 “牵一发而动全身” 的网络重塑。例如，在诱导多能干细胞（iPSC）研究中，四个转录因子（Oct4、Sox2、Klf4、c-Myc）可将成纤维细胞重编程为多能干细胞；在细胞治疗中，通过调控转录因子可诱导细胞分化为特定功能细胞，如将皮肤细胞直接重编程为神经元，用于帕金森病的治疗。
不过，识别关键转录因子是一大挑战。当前主要通过单细胞测序与CRISPR 筛选解析网络：例如，通过单细胞 RNA 测序（scRNA-seq）分析疾病细胞与正常细胞的基因表达差异，再结合 ATAC-seq（转座酶可及性染色质测序）识别开放的调控区域，进而锁定关键转录因子；随后通过 CRISPR 敲除或激活筛选，验证这些转录因子对细胞功能的影响。例如，在白血病治疗中，研究人员通过筛选发现，抑制转录因子 BCL11A 可激活胎儿血红蛋白（HbF）的表达，替代异常的成人血红蛋白，目前基于该机制的 CRISPR 编辑疗法已获批用于镰状细胞贫血和 β- 地中海贫血。（二）合成基因回路：人工设计的 “调控模块”
为了实现更复杂的细胞功能调控，科研人员借鉴电子电路原理，设计出合成基因回路，让细胞能感知环境信号并做出预设反应。在 CAR-T 细胞治疗中，传统 CAR-T 细胞因持续表达 CAR，易出现 “耗竭” 或 “脱靶毒性”，而合成基因回路可解决这一问题。
图3 SynNotch 介导的抗原触发基因表达
例如，synNotch 系统是一种 “双信号响应” 回路：synNotch 受体的 extracellular 结构域识别第一个抗原（如肿瘤细胞表面的 HER2），结合后会触发受体切割，释放 intracellular 的转录因子，进而激活第二个 CAR（如靶向 CD19）的表达。只有同时表达两种抗原的肿瘤细胞才会被 CAR-T 细胞识别并杀伤，大幅提升治疗特异性。此外，synNotch 系统还可用于 “组织特异性治疗”，如设计识别脑内特定细胞表面蛋白的 synNotch 受体，激活抗炎因子 IL-10 的表达，用于治疗神经炎症。
图4 内源性 mRNA 的感应调控
另一类RNA 感应回路则通过检测细胞内源性 RNA 实现精准调控。例如，将内部核糖体进入位点（IRES）隐藏在 RNA 茎环结构中，只有当细胞内存在特定 mRNA 时，该 mRNA 会与茎环结合，打开 IRES，启动治疗基因翻译。这类回路可用于 “细胞状态监测”，如在癌细胞中，检测到端粒酶 mRNA（癌细胞高表达）后才启动自杀基因，实现 “精准杀癌”。
图5 基因调控网络的解析与干预 （A）转录因子调控：通过解析基因调控网络，识别关键转录因子（如 BCL11A），调控其活性可同时影响多个下游基因，实现网络重塑；（B）CRISPR 筛选：通过高通量 CRISPR 筛选（如 Perturb-seq），将基因扰动与单细胞转录组结合，定位调控网络中的关键元件（如增强子），为治疗提供靶点。五、递送系统：基因调控技术的 “运输车队”
无论多么先进的基因调控工具，都需要通过递送系统到达目标细胞，才能发挥作用。递送系统的效率、特异性和安全性，直接决定基因治疗的成败。目前主流的递送系统可分为病毒载体和非病毒载体两大类。（一）病毒载体：高效但需规避风险
AAV 载体是当前体内基因治疗的 “主力载体”，具有安全性高、可长期表达的优势。天然 AAV 载体有多种血清型，不同血清型对组织的亲和力不同（如 AAV9 易靶向肌肉，AAV5 易靶向肝脏）。为了进一步提升靶向性，科研人员通过定向进化改造 AAV 衣壳：将 AAV 衣壳基因随机突变，构建突变库，在动物体内筛选能高效靶向特定组织（如大脑、肺部）的衣壳变体。例如，通过在小鼠体内筛选，获得的 AAV-PHP.B 变体对中枢神经系统的转导效率比天然 AAV9 提升 10 倍以上。
不过，AAV 载体存在两大局限：一是免疫原性，患者体内若存在 AAV 抗体，会中和载体，导致治疗失败；二是包装容量小（约 4.7kb），无法携带大型基因（如肌营养不良蛋白基因）。为解决这些问题，研究人员开发了 “AAV 衣壳人源化” 技术，减少抗体识别；同时设计 “双 AAV 载体”，将大型基因拆分为两段，分别装入两个 AAV 载体，进入细胞后再通过同源重组拼接成完整基因。
慢病毒载体则主要用于体外细胞治疗（如 CAR-T），可将基因整合到细胞基因组中，实现长期表达。但慢病毒的随机整合可能激活癌基因，因此目前多采用靶向整合技术，如通过 CRISPR-Cas9 将 CAR 基因定向插入 T 细胞的 TRAC 基因座，既避免随机整合风险，又能减少 T 细胞耗竭，提升治疗效果。（二）非病毒载体：安全但需提升效率
非病毒载体（如脂质纳米颗粒 LNP、聚合物载体）具有安全性高、可重复给药的优势，尤其适用于 RNA 药物（如 siRNA、mRNA）的递送。例如，用于治疗转甲状腺素蛋白淀粉样变性的 Patisiran，就是通过LNP递送 siRNA，靶向肝脏细胞降低 TTR 蛋白表达；2021 年获批的 CRISPR 疗法则通过 LNP 递送 Cas9 mRNA 和 sgRNA，在体内实现基因编辑。
不过，非病毒载体的递送效率仍需提升，尤其是向肝脏以外的组织（如肺部、大脑）递送时。当前研究通过 “表面修饰” 提升靶向性，如在 LNP 表面连接靶向肺部的肽段或抗体，或利用血脑屏障的特异性受体（如转铁蛋白受体）介导载体进入大脑。此外，类病毒颗粒（VLP）是新型非病毒载体，结合了病毒的高效递送能力和非病毒载体的安全性，目前已在肌肉和肝脏靶向治疗中开展预临床研究。六、挑战与未来：基因治疗如何走得更远？
尽管基因调控技术取得了显著突破，但要实现广泛临床应用，仍需克服三大核心挑战：（一）特异性与脱靶效应的平衡
当前技术虽能实现一定的组织特异性，但仍存在 “脱靶风险”。例如，CRISPR 编辑可能导致非目标位点的 DNA 切割，引发染色体异常；表观遗传编辑虽不切割 DNA，但长期调控可能影响邻近基因的表达。未来需通过 “精准靶向” 技术提升特异性，如开发更精准的 sgRNA 设计算法、利用单碱基编辑（如碱基编辑器、引导编辑器）减少双链断裂，同时加强脱靶效应的检测手段（如全基因组测序、单细胞测序）。（二）递送效率与长效性的难题
递送系统仍是基因治疗的 “瓶颈”：AAV 载体虽能长期表达，但无法重复给药；LNP 等非病毒载体虽可重复给药，但表达时间短（仅数天至数周）。未来需开发 “长效非病毒载体”，如可在细胞内缓慢释放基因的纳米颗粒，或利用干细胞作为 “基因递送工厂”，在体内持续产生治疗分子。此外，针对 “AAV 抗体阳性患者”，需开发免疫抑制方案或新型载体（如腺病毒载体、巨细胞病毒载体），扩大治疗人群。（三）临床转化与监管的适配
基因治疗的长期安全性仍需长期随访，例如 AAV 载体的整合风险、基因编辑对生殖细胞的潜在影响等。同时，临床 trial 设计需适配基因治疗的特性，如 “一次给药长期有效” 的疗法，需延长随访时间评估疗效持久性；而 “可调控疗法” 则需设计灵活的剂量调整方案。监管机构也需制定针对性的评审标准，在鼓励创新的同时保障患者安全。
未来，随着基因调控技术与递送系统的不断融合，基因治疗将从 “治疗罕见病” 向 “治疗常见病” 拓展，不仅能治愈遗传性疾病，还能为癌症、糖尿病、神经退行性疾病等复杂疾病提供个性化治疗方案。而基因调控技术，正是这场医学革命中最关键的 “精准导航仪”，让基因治疗从 “盲目探索” 走向 “精准可控”，真正实现 “以基因之力，解病痛之困”。
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免疫疗法细胞疗法基因疗法临床研究
2025-08-06
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08/06/25 4:05 PM EDT
ELEVIDYS shipments have resumed for ambulatory individuals living with Duchenne following notification from the U.S. Food and Drug Administration (FDA); continuing to work with FDA on safety labeling process and risk-mitigation approach for non-ambulatory individuals Net product revenues for the second quarter 2025 totaled $513.1 million , a 42% increase over the same quarter of the prior year Previously announced restructuring advancing as planned; on track to realize over $100 million in cost savings through the end of 2025 Multiple clinical data readouts and milestones expected in 2025 and into early 2026 to support siRNA franchise - FSHD, DM1, SCA2, and Huntington’s Disease
CAMBRIDGE, Mass. --(BUSINESS WIRE)--Aug. 6, 2025-- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today reported financial results for the second quarter of 2025.
“We are very pleased that following a rapid review of the safety data, the FDA swiftly recommended that we take the ambulatory patient population off shipment pause and, following that, we have already resumed deliveries. Infusions are taking place for the ambulatory community. We will continue to work with the FDA to define the path and develop the risk mitigation necessary to bring ELEVIDYS back to the non-ambulatory community as well,” said Doug Ingram , chief executive officer, Sarepta. “With the temporary pause lifted, the execution of our restructuring, cost savings and plans designed to meet our financial obligations, and with important siRNA readouts expected later this year, we are well positioned to achieve our strategic objective to remain a patient-centric, financially disciplined organization into the next decade and beyond.”
Corporate Highlights
ELEVIDYS Updates
On July 28, 2025 , the FDA recommended that Sarepta remove its voluntary pause and resume shipments of ELEVIDYS (delandistrogene moxeparvovec) for ambulatory individuals living with Duchenne. The notification came after the FDA completed its review of ELEVIDYS safety data. Shipments have resumed so that patient infusions can continue. Discussions between FDA and Sarepta are underway on next steps in the safety labeling process for acute liver injury/acute liver failure (ALI/ALF) and risk-mitigation approach for non-ambulatory individuals living with Duchenne.
Financial Updates
In the second quarter of 2025, the Company delivered strong financial results, reporting both GAAP and non-GAAP operating profit. The quarter was cash flow positive and total cash, cash equivalents and short- and long-term investments increased by $202.8 million from the previous quarter. The Company is taking steps to further strengthen its financial foundation and is focused on proactive liability management. Among many things, it is evaluating opportunities to enhance operational efficiency and adjust manufacturing commitments based on latest demand to further strengthen our liquidity position. The strategic restructuring announced on July 16, 2025 , will sharpen the Company’s focus on high-impact programs, particularly its siRNA platform, while reducing expenses by approximately $400 million annually starting in 2026. These strategic cost reductions and pipeline prioritization are designed to position Sarepta to repay its 2027 convertible notes and continue delivering transformative therapies to patients with rare genetic diseases.
Expected Near-Term Milestones (2025/2026)
Facioscapulohumeral muscular dystrophy (FSHD) Study Status: Phase 1/2 study of SRP-1001 FSHD1 patients underway; Cohorts 1, 2, and 3 in part 1 are fully enrolled in the single ascending dose (SAD) study Next Milestone: Preliminary data in second half of 2025 focused on safety, DUX4 mRNA knockdown, DUX4 regulated gene expression, and functional assessments Myotonic dystrophy type 1 (DM1) Study Status: Phase 1/2 study of SRP-1003 in patients with DM1 underway with recent authorization to dose escalate; Cohorts 1 and 2 in the SAD arm of the study fully enrolled Recently Achieved Collaboration Milestone: In July 2025 , the program reached the first of two pre-specified enrollment targets, and the safety review warranted dose escalation in the Phase 1/2 study, triggering $100.0 million milestone payment to Arrowhead Pharmaceuticals, Inc. (Arrowhead) Next Milestone: Preliminary Phase 1 data in second half of 2025; primary endpoint is safety, with key secondary endpoints including DMPK knockdown, DMPK-mediated splice indices, and functional assessments such as Video Hand Opening Time (VHOT) Spinocerebellar ataxia type 2 (SCA2) Study Status: Phase 1 study of SRP-1004 in patients with SCA2 underway as a randomized, placebo-controlled, SAD study, and Cohort 1 in this arm of the study has been fully enrolled Next Milestone: On track for First Participant In (FPI), Cohort 2 in the third quarter of 2025 Huntington’s Disease (HD) Sarepta intends to file its Clinical Trial Application (CTA) for SRP-1005 in HD by the end of 2025 and initiate its clinical trial in the first half of 2026
Study Status: Phase 1/2 study of SRP-1001 FSHD1 patients underway; Cohorts 1, 2, and 3 in part 1 are fully enrolled in the single ascending dose (SAD) study Next Milestone: Preliminary data in second half of 2025 focused on safety, DUX4 mRNA knockdown, DUX4 regulated gene expression, and functional assessments
Study Status: Phase 1/2 study of SRP-1003 in patients with DM1 underway with recent authorization to dose escalate; Cohorts 1 and 2 in the SAD arm of the study fully enrolled Recently Achieved Collaboration Milestone: In July 2025 , the program reached the first of two pre-specified enrollment targets, and the safety review warranted dose escalation in the Phase 1/2 study, triggering $100.0 million milestone payment to Arrowhead Pharmaceuticals, Inc. (Arrowhead) Next Milestone: Preliminary Phase 1 data in second half of 2025; primary endpoint is safety, with key secondary endpoints including DMPK knockdown, DMPK-mediated splice indices, and functional assessments such as Video Hand Opening Time (VHOT)
Study Status: Phase 1 study of SRP-1004 in patients with SCA2 underway as a randomized, placebo-controlled, SAD study, and Cohort 1 in this arm of the study has been fully enrolled Next Milestone: On track for First Participant In (FPI), Cohort 2 in the third quarter of 2025
Sarepta intends to file its Clinical Trial Application (CTA) for SRP-1005 in HD by the end of 2025 and initiate its clinical trial in the first half of 2026
2025 ASGCT Annual Conference: Sarepta showcased data spanning different age groups including statistically significant functional outcomes for 8- and 9-year-old patients, and new protein expression and safety results in participants 2 years old at the time of treatment.
Part 2 analysis of EMBARK study of 8- and 9-year-olds (n=14) demonstrated statistically significant differences across all key endpoints including 4.75 points (P=0.0026) on North Star Ambulatory Assessment (NSAA), 6.87 seconds in time-to-rise (TTR) from the floor (P=0.0010), and 4.76 seconds in 10-meter walk/run (10MWR) (P=0.0097) compared to a well-matched external control cohort Results from ENDEAVOR study show treatment in 2-year-old participants with ELEVIDYS for Duchenne muscular dystrophy resulted in mean protein expression of 93.87% as measured by western blot in study participants (n=6)
All the posters and presentations are available on the Company’s website here.
As previously announced, there will be no conference call for this quarterly earnings release.
Q2 2025 Financial Highlights1
For the Three Months Ended June 30 ,
2025
2024
QTD Change
(in millions, except for per share amounts)
$
%
Total Revenues
$
611.1
$
362.9
248.2
68
%
Operating income (loss):
GAAP
$
115.6
$
(0.7
)
116.3
NM*
Non-GAAP
$
162.8
$
57.9
104.9
181
%
Net income:
GAAP
$
196.9
$
6.5
190.4
NM*
Non-GAAP
$
215.2
$
46.5
168.7
NM*
Diluted earnings per share:
GAAP
$
1.89
$
0.07
1.82
NM*
Non-GAAP
$
2.02
$
0.43
1.59
NM*
For the Six Months Ended June 30 ,
2025
2024
YTD Change
(in millions, except for per share amounts)
$
%
Total Revenues
$
1,355.9
$
776.4
579.5
75
%
Operating (loss) income:
GAAP
$
(184.8
)
$
34.2
(219.0
)
NM*
Non-GAAP
$
(86.8
)
$
141.6
(228.4
)
NM*
Net (loss) income:
GAAP
$
(250.6
)
$
42.6
(293.2
)
NM*
Non-GAAP
$
(117.3
)
$
123.8
(241.1
)
NM*
Diluted (loss) earnings per share:
GAAP
$
(2.57
)
$
0.44
(3.01
)
NM*
Non-GAAP
$
(1.20
)
$
1.15
(2.35
)
NM*
*NM: not meaningful
[1] For an explanation of our use of non-GAAP financial measures, please refer to the “Use of Non-GAAP Financial Measures” section later in this press release and for a reconciliation of each GAAP financial measure to the most comparable non-GAAP measures, see the tables at the end of this press release.
As of June 30, 2025
As of December 31, 2024
(in millions)
Cash, cash equivalents, restricted cash and short- and long-term investments
$
850.3
$
1,503.5
Revenues Total revenues were $611.1 million for the three months ended June 30, 2025 , as compared to $362.9 million for the same period of 2024, an increase of $248.2 million . The increase primarily reflects an increase of $160.1 million in net product revenue of ELEVIDYS as a result of its expanded label approval in June 2024 . In addition, collaboration and other revenues increased $95.6 million primarily due to $63.5 million of collaboration revenue recognized related to a milestone payment received from F. Hoffman-La Roche Ltd.'s (“Roche”) for the regulatory approval of ELEVIDYS in Japan (the “Japan Approval Milestone”). Furthermore, contract manufacturing revenues and royalty revenues increased $27.0 million and $5.1 million , respectively, associated with an increase in commercial ELEVIDYS supply delivered to Roche as well as royalty revenue from sales of ELEVIDYS by Roche, respectively.
Total revenues were $1,355.9 million for the six months ended June 30, 2025 , as compared to $776.4 million for the same period of 2024, an increase of $579.5 million . The increase primarily reflects an increase of $401.2 million in net product revenue of ELEVIDYS as a result of its expanded label approval in June 2024 . In addition, collaboration and other revenues increased $174.9 million primarily related to the $63.5 million of collaboration revenue recognized from the Japan Approval Milestone and the $112.0 million of collaboration revenue recognized related to Roche's expiration of an option for a program during the six months ended June 30, 2025 , as compared to $48.0 million of collaboration revenue recognized in the same period of 2024 related to Roche’s declined option to acquire certain ex-US rights to an external, early-stage Duchenne development program. Furthermore, contract manufacturing revenues and royalty revenues increased $38.6 million and $8.8 million , respectively, associated with an increase in commercial ELEVIDYS supply delivered to Roche as well as royalty revenue from sales of ELEVIDYS by Roche, respectively.
Cost of sales (excluding amortization of in-licensed rights) Cost of sales (excluding amortization of in-license rights) were $152.6 million for the three months ended June 30, 2025 , as compared to $44.5 million for the same period of 2024, an increase of approximately $108.1 million . Cost of sales (excluding amortization of in-license rights) were $290.1 million for the six months ended June 30, 2025 , as compared to $95.1 million for the same period of 2024, an increase of $195.0 million . The increases in both periods primarily reflect the depletion of previously expensed ELEVIDYS inventory, an increased demand for ELEVIDYS following the expanded label approval in June 2024 , an increase in products sold to Roche under the Roche collaboration agreement, as well as an increase in the write-offs of certain batches of products not meeting quality specifications for the periods ended June 30, 2025 , as compared to the same periods of 2024.
Operating expenses and others Research and development expenses were $204.4 million for the three months ended June 30, 2025 , as compared to $179.7 million for the same period of 2024, an increase of $24.7 million . The increase is primarily due to an increase in ELEVIDYS clinical material expense as well as $13.0 million of costs associated with our settlement agreement with Brammer Bio MA, LLC (“Brammer”), an affiliate of Thermo Fisher Scientific, Inc., to resolve outstanding claims related to the termination of the development, commercial manufacturing, and supply agreement with Brammer (the “Brammer Settlement”). For the three months ended June 30, 2025 , non-GAAP research and development expenses were $181.7 million , as compared to $153.9 million for the same period of 2024, an increase of $27.8 million .
Research and development expenses were $977.8 million for the six months ended June 30, 2025 , as compared to $380.1 million for the same period of 2024, an increase of approximately $597.7 million . The increase primarily reflects a $583.6 million increase in up-front and milestone expense associated with the licensing and collaboration agreement and stock purchase agreement with Arrowhead, as well as $13.0 million of costs associated with the Brammer Settlement. For the six months ended June 30, 2025 , non-GAAP research and development expenses were $930.9 million , as compared to $332.0 million for the same period of 2024, an increase of $598.9 million .
Selling, general and administrative expenses were $137.9 million for the three months ended June 30, 2025 , as compared to $138.8 million for the same period of 2024, a decrease of $0.9 million . The decrease is primarily driven by a net decrease in stock-based compensation primarily due to the achievement of performance conditions related to certain PSUs during the three months ended June 30, 2024 , partially offset by an increase in professional services used for the commercialization of ELEVIDYS. For the three months ended June 30, 2025 , non-GAAP selling, general and administrative expenses were $113.4 million , as compared to $106.0 million for the same period of 2024, an increase of $7.4 million .
Selling, general and administrative expenses were $271.5 million for the six months ended June 30, 2025 , as compared to $265.8 million for the same period of 2024, an increase of $5.7 million . The increase is primarily driven by an increase in compensation and other personnel expenses as well as an increase in professional services used for the commercialization of ELEVIDYS, partially offset by a net decrease in stock-based compensation primarily due to the achievement of performance conditions related to certain PSUs during the six months ended June 30, 2024 . For the six months ended June 30, 2025 , non-GAAP selling, general and administrative expenses were $220.5 million , as compared to $206.5 million for the same period of 2024, an increase of $14.0 million .
Other income (expense), net for the three months ended June 30, 2025 and 2024, was $38.1 million and $14.3 million , respectively. Other (expense) income, net for the six months ended June 30, 2025 and 2024, was $(45.1) million and $20.8 million , respectively. The changes in each period primarily reflect the fair value adjustments of our investments in publicly-traded companies, including Arrowhead, during the periods ended June 30, 2025 .
Income tax (benefit) expense for the three months ended June 30, 2025 and 2024, was $(43.3) million and $7.1 million , respectively. Income tax expense for the six months ended June 30, 2025 and 2024, was $20.7 million and $12.4 million , respectively. Income tax (benefit) expense for all periods presented primarily relates to state, federal and foreign income taxes for which available tax losses or credits were not available to offset.
Use of Non-GAAP Measures In addition to the GAAP financial measures set forth in this press release, we have included the following non-GAAP measurements:
The following components are used to adjust our GAAP financial measures into the previously defined non-GAAP measurements:
a)
The (gain) loss on strategic investments as it is a non-cash item and the results of such gains and losses are not representative of our normal business operations, which accordingly, would make it difficult to compare our results to peer companies that also provide non-GAAP disclosures. We are making this change beginning in 2025 because, as our strategic investments have increased, we recognized that the resulting variability can impede comparability between periods of our financial performance for our ongoing business operations.
b)
The change in fair value of derivatives related to regulatory-related contingent payments meeting the definition of a derivative to Myonexus Therapeutics, Inc. selling shareholders as well as to an academic institution under a separate license agreement as these are non-cash items and are not considered to be normal operating expenses due to the variability of amounts and lack of predictability as to occurrence and/or timing.
We use these non-GAAP measures as key performance measures for the purpose of evaluating operational performance and cash requirements internally. We also believe these non-GAAP measures increase comparability of period-to-period results and are useful to investors as they provide a similar basis for evaluating our performance as is applied by management. These non-GAAP measures are not intended to be considered in isolation or to replace the presentation of our financial results in accordance with GAAP. Use of the terms non-GAAP research and development expenses, non-GAAP selling, general and administrative expenses, non-GAAP operating (loss) income, non-GAAP net (loss) income, and non-GAAP diluted (loss) earnings per share may differ from similar measures reported by other companies, which may limit comparability, and are not based on any comprehensive set of accounting rules or principles. All relevant non-GAAP measures are reconciled from their respective GAAP measures in the attached table “Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures.”
About EXONDYS 51 EXONDYS 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion, or “skipping”, of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.
EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This indication is approved under accelerated approval based on an increase in dystrophin in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
EXONDYS 51 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.
Important Safety Information About EXONDYS 51 Hypersensitivity reactions, including bronchospasm, chest pain, cough, tachycardia, and urticaria have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy.
Adverse reactions in DMD patients (N=8) treated with EXONDYS 51 30 mg or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended.
The most common adverse reactions from observational clinical studies (N=163) seen in greater than 10% of patients were headache, cough, rash, and vomiting.
Other adverse events may occur.
To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For further information, please see the full US Prescribing Information for EXONDYS 51 (eteplirsen).
About VYONDYS 53 VYONDYS 53 (golodirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.
VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
VYONDYS 53 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.
Important Safety Information for VYONDYS 53
CONTRAINDICATIONS: VYONDYS 53 is contraindicated in patients with a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53. Anaphylaxis has occurred in patients receiving VYONDYS 53.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in VYONDYS 53-treated patients, some requiring treatment. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting, or discontinuing the VYONDYS 53 therapy and monitor until the condition resolves. VYONDYS 53 is contraindicated in patients with a history of a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53.
Kidney Toxicity: Kidney toxicity was observed in animals who received golodirsen. Although kidney toxicity was not observed in the clinical studies with VYONDYS 53, the clinical experience with VYONDYS 53 is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking VYONDYS 53. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VYONDYS 53. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting VYONDYS 53. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every three months. Only urine expected to be free of excreted VYONDYS 53 should be used for monitoring of urine protein. Urine obtained on the day of VYONDYS 53 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any VYONDYS 53 that is excreted in the urine and thus lead to a false positive result for urine protein.
If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.
ADVERSE REACTIONS: Adverse reactions observed in at least 20% of treated patients and greater than placebo were (VYONDYS 53, placebo): headache (41%, 10%), pyrexia (41%, 14%), fall (29%, 19%), abdominal pain (27%, 10%), nasopharyngitis (27%, 14%), cough (27%, 19%), vomiting (27%, 19%), and nausea (20%, 10%).
Other adverse reactions that occurred at a frequency greater than 5% of VYONDYS 53-treated patients and at a greater frequency than placebo were: administration site pain, back pain, pain, diarrhea, dizziness, ligament sprain, contusion, influenza, oropharyngeal pain, rhinitis, skin abrasion, ear infection, seasonal allergy, tachycardia, catheter site related reaction, constipation, and fracture.
Other adverse events may occur.
To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For further information, please see the full US Prescribing Information for VYONDYS 53 (golodirsen).
About AMONDYS 45 AMONDYS 45 (casimersen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.
AMONDYS 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
AMONDYS 45 has met the full statutory standards for safety and effectiveness and as such is not considered investigational or experimental.
Important Safety Information for AMONDYS 45
CONTRAINDICATION: AMONDYS 45 is contraindicated in patients with a known serious hypersensitivity to casimersen or any of the inactive ingredients in AMONDYS 45. Instances of hypersensitivity including angioedema and anaphylaxis have occurred.
WARNINGS AND PRECAUTIONS
Hypersensitivity: Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with AMONDYS 45. If a hypersensitivity reaction occurs, institute appropriate medical treatment, and consider slowing the infusion, interrupting, or discontinuing the AMONDYS 45 infusion and monitor until the condition resolves. AMONDYS 45 is contraindicated in patients with known serious hypersensitivity to casimersen or to any of the inactive ingredients in AMONDYS 45.
Kidney Toxicity: Kidney toxicity was observed in animals who received casimersen. Although kidney toxicity was not observed in the clinical studies with AMONDYS 45, kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking AMONDYS 45. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting AMONDYS 45. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting AMONDYS 45. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein to-creatinine ratio (UPCR) every three months. Only urine expected to be free of excreted AMONDYS 45 should be used for monitoring of urine protein. Urine obtained on the day of AMONDYS 45 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any AMONDYS 45 that is excreted in the urine and thus lead to a false positive result for urine protein.
If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.
Adverse Reactions: Adverse reactions occurring in at least 20% of patients treated with AMONDYS 45 and at least 5% more frequently than in the placebo group were (AMONDYS 45, placebo): upper respiratory infections (65%, 55%), cough (33%, 26%), pyrexia (33%, 23%), headache (32%, 19%), arthralgia (21%, 10%), and oropharyngeal pain (21%, 7%).
Other adverse reactions that occurred in at least 10% of patients treated with AMONDYS 45 and at least 5% more frequently than in the placebo group were: ear pain, nausea, ear infection, post-traumatic pain, and dizziness and light-headedness.
Other adverse events may occur.
To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For further information, please see the full US Prescribing Information for AMONDYS 45 (casimersen).
About ELEVIDYS (delandistrogene moxeparvovec-rokl) ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle.
ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.
For patients who are ambulatory and have a confirmed mutation in the DMD gene For patients who are non-ambulatory and have a confirmed mutation in the DMD gene.
The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Safety Information for ELEVIDYS
CONTRAINDICATION: ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.
WARNINGS AND PRECAUTIONS:
Infusion-related Reactions:
Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration. Closely monitor patients during administration and for at least 3 hours after the end of infusion. If symptoms of infusion-related reactions occur, slow, or stop the infusion and give appropriate treatment. Once symptoms resolve, the infusion may be restarted at a lower rate. ELEVIDYS should be administered in a setting where treatment for infusion-related reactions is immediately available. Discontinue infusion for anaphylaxis.
Acute Serious Liver Injury:
Acute serious liver injury has been observed with ELEVIDYS, and administration of ELEVIDYS may result in elevations of liver enzymes (e.g., GGT, GLDH, ALT, AST) or total bilirubin, typically seen within 8 weeks. Patients with preexisting liver impairment, chronic hepatic condition, or acute liver disease (e.g., acute hepatic viral infection) may be at higher risk of acute serious liver injury. Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled. Prior to ELEVIDYS administration, perform liver enzyme test and monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT and total bilirubin levels return to near baseline levels). Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion. Adjust corticosteroid regimen when indicated. If acute serious liver injury is suspected, a consultation with a specialist is recommended.
Immune-mediated Myositis:
In clinical trials, immune-mediated myositis has been observed approximately 1 month following ELEVIDYS infusion in patients with deletion mutations involving exon 8 and/or exon 9 in the DMD gene. Symptoms of severe muscle weakness including dysphagia, dyspnea and hypophonia were observed. Limited data are available for ELEVIDYS treatment in patients with mutations in the DMD gene between exons 1 to 17 and exons 59 to 71. Patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction. Advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea or hypophonia as these may be symptoms of myositis. Consider additional immunomodulatory treatment (immunosuppressants [e.g., calcineurin-inhibitor] in addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur.
Myocarditis:
Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYS infusion in clinical trials. If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Monitor troponin-I before ELEVIDYS infusion and weekly for the first month following infusion and continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath. Advise patients to contact a physician immediately if they experience cardiac symptoms.
Pre-existing Immunity against AAVrh74:
In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with ELEVIDYS, all subjects developed anti-AAVrh74 antibodies. Perform baseline testing for the presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYS administration. ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers greater than or equal to 1:400.
Adverse Reactions:
The most common adverse reactions (incidence ≥ 5%) reported in clinical studies were vomiting, nausea, liver function test increased, pyrexia, and thrombocytopenia.
Report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Sarepta Therapeutics at 1-888-SAREPTA (1-888-727-3782).
For further information, please see the full Prescribing Information for ELEVIDYS (delandistrogene moxeparvovec-rokl).
About Sarepta Therapeutics Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (Duchenne) and are building a robust portfolio of programs across muscle, central nervous system, and cardiac diseases. For more information, please visit www.sarepta.com or follow us on LinkedIn, X, Instagram and Facebook.
Forward-Looking Statements In order to provide Sarepta’s investors with an understanding of its current results and future prospects, this press release contains statements that are forward-looking. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “will,” “may,” “intends,” “prepares,” “looks,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements relating to our future operations, financial performance and projections, business plans, market opportunities, priorities and research and development programs and technologies; our clinical trials; the potential benefits of our technologies and scientific approaches; ongoing discussions with FDA related to ELEVIDYS, including the safety labeling process and risk-mitigation approach for non-ambulatory individuals; and expected plans and milestones, including multiple clinical data readouts and milestones expected in 2025 and into early 2026 for our siRNA franchise and working with FDA to resume shipments of ELEVIDYS to non-ambulatory individuals.
These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta’s control. Actual results could materially differ from those stated or implied by these forward-looking statements as a result of such risks and uncertainties. Known risk factors include the following: we may not be able to comply with all FDA post-approval commitments and requirements with respect to our products in a timely manner or at all; our products or product candidates may be perceived as insufficiently effective, unsafe or may result in unforeseen adverse events; our products or product candidates may cause undesirable side effects that result in significant negative consequences following any marketing approval; success in preclinical and clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and the results of future research may not be consistent with past positive results or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; certain programs may never advance in the clinic or may be discontinued for a number of reasons, including regulators imposing a clinical hold and us suspending or terminating clinical research or trials; if the actual number of patients suffering from the diseases we aim to treat is smaller than estimated, our revenue and ability to achieve profitability may be adversely affected; we may not be able to execute on our business plans, including meeting our expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing our product candidates to market, for various reasons, some of which may be outside of our control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, the COVID-19 pandemic and regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates; and those risks identified under the heading “Risk Factors” in our most recent Annual Report on Form 10-K for the year ended December 31, 2024 and our most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review.
Internet Posting of Information We routinely post information that may be important to investors in the 'For Investors' section of our website at www.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.
Sarepta Therapeutics, Inc.
Condensed Consolidated Statements of Income (Loss)
(unaudited, in thousands, except per share amounts)
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
Revenues:
Products, net
$
513,123
$
360,548
$
1,124,646
$
720,032
Collaboration and other
97,968
2,383
231,301
56,363
Total revenues
611,091
362,931
1,355,947
776,395
Cost and expenses:
Cost of sales (excluding amortization of in-licensed rights)
152,558
44,545
290,122
95,104
Research and development
204,392
179,690
977,840
380,086
Selling, general and administrative
137,897
138,796
271,526
265,799
Amortization of in-licensed rights
667
601
1,268
1,202
Total cost and expenses
495,514
363,632
1,540,756
742,191
Operating income (loss)
115,577
(701
)
(184,809
)
34,204
Other income (loss), net:
Other income (expense), net
38,061
14,278
(45,071
)
20,821
Total other income (loss), net
38,061
14,278
(45,071
)
20,821
Income (loss) before income tax expense
153,638
13,577
(229,880
)
55,025
Income tax (benefit) expense
(43,254
)
7,117
20,736
12,446
Net income (loss)
$
196,892
$
6,460
$
(250,616
)
$
42,579
Earnings (loss) per share:
Basic
$
2.01
$
0.07
$
(2.57
)
$
0.45
Diluted
$
1.89
$
0.07
$
(2.57
)
$
0.44
Weighted average number of shares of common stock used in computing earnings (loss) per share:
Basic
98,005
94,618
97,685
94,305
Diluted
106,623
99,144
97,685
99,129
Sarepta Therapeutics, Inc.
Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures
(unaudited, in thousands, except per share amounts)
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
GAAP net income (loss)
$
196,892
$
6,460
$
(250,616
)
$
42,579
Interest income, net
(1,921
)
(14,010
)
(9,846
)
(29,741
)
Depreciation and amortization expense
10,173
8,118
19,550
16,261
Stock-based compensation expense
37,025
50,482
78,453
91,174
Change in fair value of derivatives
—
—
—
10,100
(Gain) loss on strategic investments*
(36,721
)
(148
)
54,007
(1,079
)
Income tax effect of adjustments
9,728
(4,389
)
(8,870
)
(5,472
)
Non-GAAP net income (loss)
$
215,176
$
46,513
$
(117,322
)
$
123,822
GAAP net earnings (loss) per share - diluted:
$
1.89
$
0.07
$
(2.57
)
$
0.44
Add: impact of GAAP to Non-GAAP adjustments
$
0.13
$
0.36
$
1.37
$
0.71
Non-GAAP net earnings (loss) per share - diluted**
$
2.02
$
0.43
$
(1.20
)
$
1.15
Weighted average number of shares of common stock used in computing diluted earnings (loss) per share:***
GAAP
106,623
99,144
97,685
99,129
Non-GAAP
106,623
107,245
97,685
107,230
*Beginning in the first quarter of 2025, (gain) loss on strategic investments was included as a non-GAAP measurement to adjust our GAAP financial measures. Non-GAAP financial results for the three and six months ended June 30, 2024 , have been updated to reflect this change for comparability. Please refer to the “Use of Non-GAAP Measures” section above for additional detail.
**Non-GAAP earnings per share is calculated using diluted shares whereas non-GAAP net loss per share is calculated using basic shares as all other instruments are anti-dilutive.
***The difference between the weighted average number of shares of common stock used in computing diluted GAAP and non-GAAP earnings per share for the three and six months June 30, 2024 , is a result of the exclusion of the potential share settlement of the 2027 Convertible Notes from the GAAP earnings per share as the inclusion of such shares was anti-dilutive during those periods.
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
Total effective tax rate, GAAP
(28.2
)%
8.4
%
(9.0
)%
22.6
%
Less: impact of GAAP to Non-GAAP adjustments
(4.4
)
(4.6
)
(25.0
)
(10.0
)
Total effective tax rate, Non-GAAP
(32.6
)%
3.8
%
(34.0
)%
12.6
%
Sarepta Therapeutics, Inc.
Reconciliation of GAAP Financial Measures to Non-GAAP Financial Measures
(unaudited, in thousands)
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
GAAP research and development expenses
$
204,392
$
179,690
$
977,840
$
380,086
Stock-based compensation expense
(15,277
)
(19,806
)
(32,594
)
(36,079
)
Depreciation and amortization expense
(7,397
)
(5,982
)
(14,374
)
(12,028
)
Non-GAAP research and development expenses
$
181,718
$
153,902
$
930,872
$
331,979
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
GAAP selling, general and administrative expenses
$
137,897
$
138,796
$
271,526
$
265,799
Stock-based compensation expense
(21,748
)
(30,676
)
(45,859
)
(55,095
)
Depreciation expense
(2,776
)
(2,136
)
(5,176
)
(4,233
)
Non-GAAP selling, general and administrative expenses
$
113,373
$
105,984
$
220,491
$
206,471
For the Three Months Ended June 30 ,
For the Six Months Ended June 30 ,
2025
2024
2025
2024
GAAP operating income (loss)
$
115,577
$
(701
)
$
(184,809
)
$
34,204
Stock-based compensation expense
37,025
50,482
78,453
91,174
Depreciation and amortization expense
10,173
8,118
19,550
16,261
Non-GAAP operating income (loss)
$
162,775
$
57,899
$
(86,806
)
$
141,639
Sarepta Therapeutics, Inc.
Condensed Consolidated Balance Sheets
(unaudited, in thousands, except share and per share data)
As of June 30, 2025
As of December 31, 2024
Assets
Current assets:
Cash and cash equivalents
$
510,598
$
1,103,010
Short-term investments
289,541
251,782
Accounts receivable, net
527,295
601,988
Inventory
994,036
749,960
Manufacturing-related deposits and prepaids
207,921
276,262
Other current assets
127,594
90,461
Total current assets
2,656,985
3,073,463
Property and equipment, net
371,857
340,336
Right of use assets
143,041
148,310
Non-current inventory
194,668
187,986
Strategic investments
195,522
3,710
Non-current investments
34,604
133,163
Other non-current assets
83,137
76,205
Total assets
$
3,679,814
$
3,963,173
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable
$
136,702
$
214,442
Accrued expenses
377,399
373,513
Deferred revenue, current portion
395,431
130,256
Other current liabilities
10,416
13,473
Total current liabilities
919,948
731,684
Long-term debt
1,139,458
1,137,124
Lease liabilities, net of current portion
214,419
192,473
Deferred revenue, net of current portion
—
325,000
Contingent consideration
47,400
47,400
Other non-current liabilities
1,204
1,750
Total liabilities
2,322,429
2,435,431
Stockholders’ equity:
Preferred stock, $0.0001 par value, 3,333,333 shares authorized; none issued and outstanding
—
—
Common stock, $0.0001 par value, 198,000,000 shares authorized; 98,356,950 and 97,706,074 issued and outstanding, respectively, at June 30, 2025 and 96,900,496 issued and outstanding at December 31, 2024
10
10
Treasury stock, at cost, 650,876 and 0 shares at June 30, 2025 and December 31, 2024 , respectively
(25,263
)
—
Additional paid-in capital
5,844,279
5,738,924
Accumulated other comprehensive loss, net of tax
(51
)
(218
)
Accumulated deficit
(4,461,590
)
(4,210,974
)
Total stockholders’ equity
1,357,385
1,527,742
Total liabilities and stockholders’ equity
$
3,679,814
$
3,963,173
Source: Sarepta Therapeutics, Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20250806510848/en/
Investor Contact: Ian Estepan , 617-274-4052 iestepan@sarepta.com
Media Contact: Tracy Sorrentino , 617-301-8566 tsorrentino@sarepta.com
Source: Sarepta Therapeutics, Inc.
This section of our website may contain dated or archived information which should not be considered current and may no longer be accurate. For current information, you are encouraged to review our most recent official corporate documents on file with the U.S. Securities and Exchange Commission.
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临床1期财报临床结果
2025-07-13
·同写意
同写意年度巨献！！大会特设“体内Car-T与细胞药物前沿”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”！7月11日，FDA以缺乏支持数据为由，拒绝批准Capricor Therapeutics用于治疗杜氏肌营养不良症（DMD）相关心肌病的细胞疗法Deramiocel，公司股价一度暴跌超50%。Deramiocel，研发代号CAP-1002，由同种异体心脏球来源细胞（CDCs）组成。研究表明，CDCs可在DMD等营养不良症中发挥免疫调节和抗纤维化作用，以维持心脏和骨骼肌功能。Capricor首席执行官Linda Marbán表示，对FDA发出完整回复函（CRL）的决定感到“惊讶”，并指出在遭到拒绝之前，“审查进展顺利，没有出现重大问题，包括成功通过许可前检查和完成中期审查”。然而，上个月底，人们对Deramiocel批准的担忧就已经浮出水面，因为FDA取消了原定于8月31日举行针对该疗法审批的咨询委员会会议。Capricor当时表示，7月中旬将举行一次面对面的后期审查会议。Oppenheimer分析师在随后不久的报告中认为，Deramiocel不太会获得批准，而Capricor可能会收到CRL。不到一个月，一语成谶。7月12日，Levi & Korsinsky通知投资者，它已开始对Capricor进行调查，以弄清楚其是否违反联邦证券法。TONACEA01额外的数据FDA在CRL中表示，由于Deramiocel的上市申请不符合实质性有效性证据的法定要求，并且需要进一步的临床数据，因此无法批准。CRL还提到该申请中CMC部分的一些未解决事项。不过，Capricor表示其中大部分事项已在之前的沟通中得到解决。此次申请基于HOPE-2中期试验及其开放标签扩展试验（OLE）的结果，以及FDA资助数据集的自然史比较结果。HOPE-2研究在2018年3月1日至2020年3月31日期间，共入组26名DMD男性患者，其中8名被随机分配至Deramiocel组，12名分配至安慰剂组（由于筛选失败，有6名未进行随机分配）。在完成治疗后PUL 1.2评估的患者中（Deramiocel组有8名，安慰剂组有11名），12个月的基线变化在中位肘部 PUL1.2方面，Deramiocel组优于安慰剂组。安全性上，观察到3名患者出现与输注相关的超敏反应，但无长期后遗症，其中一名患者因严重过敏反应而停止治疗。未观察到其他重大不良反应，且无死亡病例。Marbán表示，公司“计划提交HOPE-3 III期试验的数据……以便通过一项充分且控制良好的研究，提供进一步的有效性证据”。HOPE-3的最终结果预计将于今年第三季度公布。在7月11日电话会议上，Marbán指出，公司没有必要重新提交申请，而是在对CRL做出回应后，FDA的审查将重新开始。“我们仍然非常希望这个问题能够相对容易地得到解决，虽然会有一些挫折......但不会造成重大挫折。”Oppenheimer分析师此前指出，如果HOPE-3研究成功，可能使Deramiocel在2026年下半年获得批准。根据预测，如果在美国获批，Deramiocel到2030年的销售额可能达到10亿美元左右。TONACEA02监管风波临床前和临床研究中，Deramiocel凭借其免疫调节、抗纤维化及再生潜力，先后获得FDA的孤儿药资格、再生医学先进疗法（RMAT）资格、罕见儿科疾病资格。Capricor强调，Deramiocel的整个开发过程都遵循了FDA的指导。这似乎暗示FDA“变卦”。今年1月，Capricor提交Deramiocel的上市申请时，FDA负责审查CGT的治疗产品办公室（OTP）尚由Nicole Verdun，而长期支持这一赛道的Peter Marks，也还在FDA生物制品审评与研究中心（CBER）主任一职。然而，Marks在3月已经被特朗普政府赶下台。6月，Verdun也被行政休假并被护送离开该机构。FDA最近的重组和裁员意味着，提供开发指导和裁定该上市申请的人员，可能与签发CRL的人员有所不同。 虽然Capricor措手不及，但如果放在更长的历史中，一波三折不算多意外。自2016年Sarepta开发的DMD疗法获得颇具争议的批准以来，DMD一直是FDA的敏感议题。九年前，这款名为Exondys 51的药物凭借其抗肌萎缩蛋白生成数据获得FDA的批准，但并未显示出实际的临床益处，例如改善病情进展指标。即使在FDA内部，意见也存在分歧；事实上，两位反对批准的官员最终决定退休。相比之下，欧洲监管机构在同一时期，则两次否决了Exondys 51的审批。2019 年，FDA还加速批准了Sarepta开发的另一款DMD药物Vyondys 53。但就在此前几个月，FDA曾给其发出CRL。这引发了更多争议。JonesTrading分析师指出，由于原定于8月31日举行的咨询委员会会议被取消，以及细胞疗法主要监管机构CBER的关键官员被解雇，Deramiocel在8份获得批准的可能性不大。5月，Vinay Prasad被任命为CBER主任，业界普遍觉得，鉴于这位新负责人长期对单臂试验和加速审批存在批评，CGT领域将面临更严格的监管审查。TONACEA03“Capricor们”2025年第一季度，Capricor报告净亏损约2440万美元。截至2025年3月31日，其现金头寸约为1.448亿美元。考虑到当前的投资市场环境，Capricor此番受挫，意味着其容错空间的进一步收窄。DealForma数据显示，2024年基因疗法方面的并购总额仅为12亿美元，2025年迄今为止更是没有。至于基因疗法研究合作，预付款已从2017年17亿美元峰值降至2024年的1.55亿美元。安全性问题，正在萦绕着这些投身其中的药企。3月，Sarepta开发的Elevidys并没有等来完全批准，而是意外死亡——一名16岁男性患者在接受Elevidys治疗后因急性肝衰竭死亡；三个月后，第二例死亡患者也急性肝衰竭有关。Sarepta并非唯一的受挫者。5月，另一家Biotech Rocket Pharmaceuticals也宣布，其正在进行的一项II期临床中，一名受试者在给药RP-A1501后离世。消息披露当天，Rocket股价下跌近60%，几天后FDA叫停相关试验。2025年由Elevidys开启的安全性质疑，是影响深远的。Jefferies分析师称，自那以来，投资者的幻想越来越破灭，如此观点得到越来越多共鸣：基因疗法整体上来说不值得投资，为什么还要费心关注？事实上，已经有不少MNC正在离场。2月，辉瑞以患者接受度低为由，将一款上市不到一年的血友病基因疗法Beqvez撤出市场。这意味着，作为“宇宙大药厂”的辉瑞几乎完全退出基因疗法赛道。随后的3月，罗氏宣布，对其基因疗法子公司Spark Therapeutics进行“根本性重组”。约六年前，罗氏将之收购以增强自身基因治疗业务。而据报道，今年有超过300个岗位面临裁员，这引发人们对Spark能否继续存在的质疑。Biotech股票同样在走低：过去十二个月，Solid Biosciences和Regenxbio都下跌了近30%。Leerink Partners分析师表示，很多投资者对基因疗法的情绪，“介于不感兴趣和厌恶之间”。基因疗法并非没有成功突围者。可这并不能阻止产业之问：2025年以后，留给“Capricor们”的未来还会好吗？参考资料：FDA rejects approval of Capricor's cell therapy for DMDFDA rejects Capricor’s DMD cell therapy, asks for more dataCapricor shares turn red as FDA plans deramiocel adcomm, likely the first under new commissionerCapricor shares sink as US FDA declines to approve cell therapyPotential Securities Fraud: Levi & Korsinsky Investigates Capricor Therapeutics, Inc. (CAPR)
细胞疗法免疫疗法临床3期
100 项与 Golodirsen 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11707 | Golodirsen |
研发状态
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 杜氏肌营养不良症 | 美国 | 2019-12-12 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床3期 | 171 | (Golodirsen) | 構淵製艱積衊積夢簾淵 = 壓築製繭積壓窪鏇膚膚 醖獵醖構憲簾構壓糧鑰 (鑰網襯蓋憲糧鑰餘蓋餘, 淵襯簾憲觸構淵膚憲繭 ~ 憲繭膚網鏇遞糧淵鬱願) 更多 | - | 2024-09-19 | ||
(Casimersen) | 構淵製艱積衊積夢簾淵 = 鏇築淵顧鏇遞艱網鏇網 醖獵醖構憲簾構壓糧鑰 (鑰網襯蓋憲糧鑰餘蓋餘, 鬱構齋築艱築遞製淵憲 ~ 獵淵鏇糧鑰願鏇範醖網) 更多 | ||||||
临床1/2期 | 杜氏肌营养不良症 exon 53 | 20 | 願窪繭壓鹽範網鹹範鬱(糧願窪窪鑰築觸觸齋艱) = 夢鑰夢餘鹹顧壓鹽獵窪 廠蓋積艱範衊壓簾蓋衊 (夢選顧醖積獵鹽築夢襯, 1.8) 更多 | 积极 | 2024-03-03 | ||
(Mutation-matched External Controls) | 願窪繭壓鹽範網鹹範鬱(糧願窪窪鑰築觸觸齋艱) = 艱齋壓範積淵糧齋廠鬱 廠蓋積艱範衊壓簾蓋衊 (夢選顧醖積獵鹽築夢襯, 1.3) 更多 | ||||||
N/A | - | 鹹範衊衊構蓋選繭醖觸(糧淵壓餘鑰膚鏇製範鏇) = treatment-emergent adverse events were generally mild, nonserious, and unrelated to treatment; there were no treatment-related discontinuations, kidney abnormalities, or port-related infections in the OLE 鹽積鏇窪願製選獵襯憲 (夢遞艱製衊獵廠醖蓋鑰 ) | - | 2024-03-03 | |||
(External Controls) | |||||||
临床2期 | 3 | (AMONDYS 45) | 遞鹹蓋網窪衊願遞齋鏇(構蓋窪夢壓蓋遞選積壓) = 醖廠糧觸壓網繭觸衊遞 艱窪醖遞淵遞簾遞壓壓 (淵簾糧觸淵膚鑰蓋鬱鹽, 1.8) 更多 | - | 2023-10-12 | ||
(EXONDYS 51) | 網鹽鬱醖積鏇鑰襯膚蓋(窪築繭齋鑰範壓壓積獵) = 觸獵蓋餘積醖構壓遞醖 築鑰廠鹽夢膚窪餘鏇艱 (遞艱鹹齋壓顧艱襯衊鬱, 簾積遞淵淵鹽糧願窪蓋 ~ 艱夢膚製窪壓廠製顧顧) 更多 | ||||||
临床1/2期 | 25 | 構壓齋鹽鑰糧衊膚顧膚(夢鬱願觸積膚夢願願襯) = 鬱簾廠獵選淵構憲積壓 鏇選遞餘糧築獵鏇選憲 (艱範願糧積構範構鹽築 ) 更多 | 积极 | 2022-02-01 | |||
external controls | 構壓齋鹽鑰糧衊膚顧膚(夢鬱願觸積膚夢願願襯) = 艱壓艱膚網鏇選範鹹齋 鏇選遞餘糧築獵鏇選憲 (艱範願糧積構範構鹽築 ) | ||||||
临床1/2期 | 39 | 齋獵壓鏇願廠鑰觸製蓋(構壓簾鹹蓋齋築膚夢鹹) = 鑰鏇製選窪獵製餘鑰衊 艱廠淵製鬱網繭觸構艱 (蓋獵醖觸構齋衊夢鹽繭 ) | - | 2020-05-26 |
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