主要目的：评价viltolarsen以每周80 mg/kg的剂量静脉给药(IV)治疗能走动和卧床的≥8岁DMD男孩的安全性和耐受性。次要目的：与自然病程对照相比，以每周80 mg/kg的剂量静脉给药viltolarsen48周治疗能走动和卧床的≥8岁DMD男孩的疗效。探索性目的：评价viltolarsen治疗对患者DMD健康相关生活质量的影响，评价DMD患者的咳嗽强度，评价DMD患者走动能力的保留情况，评价日常活动和睡眠-觉醒模式，以探索viltolarsen治疗对患者DMD的影响。

开始日期2022-03-17

申办/合作机构

杭州泰格医药科技股份有限公司

[+1]

NCT04956289 / Completed临床2期

A Phase 2 Open-label Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With Duchenne Muscular Dystrophy (DMD) Compared to Natural History Controls

This is a phase II, open-label study where weekly doses of 80 mg/kg viltolarsen is administered intravenously over a 48-week treatment period to ambulant and non-ambulant DMD patients over the age of 8 years.

开始日期2021-07-01

申办/合作机构

NS Pharma, Inc.

[+1]

NCT04687020 / Active, not recruiting临床4期

Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)

The VILT-502 study is Non-interventional Study(United States)/Low-intervention Clinical Trial (Canada) of Viltolarsen administered intravenously once weekly for 10 years to boys with DMD who complete the NS-065/NCNP-01-202 study.

开始日期2021-06-10

申办/合作机构

NS Pharma, Inc.

100 项与维托拉生相关的临床结果

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100 项与维托拉生相关的转化医学

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100 项与维托拉生相关的专利（医药）

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项与维托拉生相关的文献（医药）

2024-09-01·DRUG METABOLISM AND DISPOSITION

The Usefulness of Determining Plasma and Tissue Concentrations of Phosphorodiamidate Morpholino Oligonucleotides to Estimate Their Efficacy in Duchenne Muscular Dystrophy Patients

Article

作者: Mori, Jumpei ; Kameyama, Tsubasa ; Mitamura, Rei ; Imai, Shunji ; Yamada, Tetsuhiro ; Watanabe, Naoki ; Kusano, Kazutomi ; Tone, Yuichiro

Currently, four kinds of phosphorodiamidate morpholino oligomers (PMOs), such as viltolarsen, have been approved for the treatment of Duchenne muscular dystrophy (DMD); however, it is unclear whether human efficacy can be estimated using plasma concentrations. This study summarizes the tissue distribution of viltolarsen in mice and cynomolgus monkeys and evaluates the relationship between exposure and efficacy based on exon skipping. In the tissue distribution studies, all muscles in DMD-model mice showed higher concentrations of viltolarsen than those in wild-type mice and cynomolgus monkeys, and the concentrations in skeletal muscle were correlated with the exon-skipping efficiency in mice and cynomolgus monkeys. In addition, a highly sensitive bioanalytical method using liquid chromatography with tandem mass spectrometry shows promise for determining plasma concentrations up to a later time point, and the tissue (muscle)/plasma concentration ratio (Kp) in DMD-model mice was shown to be useful for predicting changes in pharmacodynamic (PD) markers in humans. Our results suggest that pharmacokinetic (PK)/PD analysis can be conducted by using the human PK profile or Kp values and skipping efficiency in DMD-model mice. This information will be useful for the efficient and effective development of PMOs as therapeutic agents. SIGNIFICANCE STATEMENT: We evaluated the relationship between the plasma or tissue concentrations and the efficiency of exon skipping for viltolarsen as an example phosphorodiamidate morpholino oligomers in the skeletal and cardiac muscle of mice and cynomolgus monkeys for pharmacokinetic/pharmacodynamic (PK/PD) analysis. The results suggest that PK/PD analysis can be conducted by using the human PK profile or tissue (muscle)/plasma concentration ratios and skipping efficiency in DMD-model mice.

2024-09-01·ADVANCES IN THERAPY

Correction to: Evolving Role of Viltolarsen for Treatment of Duchenne Muscular Dystrophy

作者: Shekoohi, Sahar ; Armstrong, Catherine J ; Dautel, Alexandra D ; Lauck, Lillian V ; McGregor, David ; Vincik, LeighAnn Y ; Staples, Abigail A ; Ahmadzadeh, Shahab ; Howard, Jeffery T ; Kaye, Alan D

2024-07-01·BIODRUGS

Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs

Review

作者: Rasmussen, Theodore P ; Manautou, José E ; Bahal, Raman ; Bochanis, Adara ; Zhong, Xiao-Bo ; Zhuo, Selena ; Sang, Angela

Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].

项与维托拉生相关的新闻（医药）

2024-10-15

·PRNewswire

NS Pharma's Galactic53 Trial Data Is Published in Scientific Reports

PARAMUS, N.J., Oct. 15, 2024 /PRNewswire/ -- NS Pharma, Inc. (NS Pharma), a subsidiary of Nippon Shinyaku Co., Ltd. (Nippon Shinyaku), announced that the Galactic53 study of VILTEPSO® (generic name: viltolarsen) – a treatment for Duchenne muscular dystrophy (Duchenne) – has been published in the journal Scientific Reports. The paper, "Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy", contains data from an open-label multicenter study, which was the first to evaluate the effects of viltolarsen on pulmonary function in participants with Duchenne. Continue Reading Ten ambulatory and ten nonambulatory participants ages eight years and older – with a confirmed deletion of the dystrophin gene that could be treated by exon 53 skipping – received 80 mg/kg of the drug intravenously once weekly for 48 weeks. Safety was evaluated as the primary endpoint, and pulmonary and motor function were evaluated as secondary efficacy endpoints. The pulmonary endpoints were compared to natural history data with matched patient backgrounds as a control group. Both ambulatory and nonambulatory participants receiving viltolarsen experienced improved pulmonary function. Post this "We're encouraged by these results for patients with exon 53 skip-amenable mutations," explains NS Pharma Vice President Medical Affairs & Pharmacovigilance Leslie Magnus, MD, who co-authored the study. "We're especially glad to report positive data was seen in both nonambulatory and ambulatory patients." All treatment-emergent adverse events were mild or moderate. Four were considered treatment-related, and no participants discontinued. The side effect profile seen in this study is consistent with that reported in previous studies, and the treatment was well tolerated. Both ambulatory and nonambulatory participants receiving viltolarsen experienced improved pulmonary function with higher percent predicted forced vital capacity (FVC%p) and higher peak cough flow (PCF) at Week 49 compared with controls. Ninety (90)% (nine / ten) of nonambulatory participants receiving viltolarsen had an increase or stabilization in FVC%p from baseline, and 60% (six / ten) of participants maintained FVC%p values >50% at Week 49, which is the recommended threshold for needing cough assist and nighttime ventilation interventions. For ambulatory participants treated with viltolarsen, 90% (nine / ten) of viltolarsen treated participants had an increase or stabilization in FVC%p from baseline, and all treated participants maintained FVC%p values >50% at Week 49. Viltolarsen treated participants, including those who were nonambulant, also showed stabilized arm strength and mobility as assessed by performance of upper limb (PUL) scores over the 48-week treatment period. About VILTEPSO® (Viltolarsen) Injection Prior to its approval in the U.S. in August 2020, VILTEPSO was granted Priority Review as well as Rare Pediatric Disease, Orphan Drug and Fast Track Designations. In March 2020, VILTEPSO was approved in Japan for the treatment of patients with Duchenne who are amenable to exon 53 skipping therapy. Prior to its approval in Japan, VILTEPSO was granted the SAKIGAKE designation, orphan drug designation, and designation of Conditional Early Approval System. Indication VILTEPSO 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 VILTEPSO. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information Warnings and Precautions: Kidney toxicity was observed in animals who received viltolarsen. Although kidney toxicity was not observed in the clinical studies with VILTEPSO, the clinical experience with VILTEPSO 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 VILTEPSO. Serum creatinine may not be a reliable measure of kidney function in patients with Duchenne. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VILTEPSO. Consider also measuring glomerular filtration rate before starting VILTEPSO. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every three months. Urine should be free of excreted VILTEPSO for monitoring of urine protein. Obtain urine either prior to VILTEPSO infusion, or at least 48 hours after the most recent infusion. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, which has the potential to generate a false positive result due to cross reaction with any VILTEPSO in the urine. If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation. Adverse Reactions: The most common adverse reactions include upper respiratory tract infection, injection site reaction, cough, and pyrexia. To report an adverse event, or for general inquiries, please call NS Pharma Medical Information at 1-866-NSPHARM (1-866-677-4276) For more information about VILTEPSO, see full Prescribing Information. About Duchenne Muscular Dystrophy Duchenne is a progressive form of muscular dystrophy that occurs primarily in males. It causes progressive weakness and loss of skeletal, cardiac, and respiratory muscles. Early signs of Duchenne may include delayed ability to sit, stand or walk. There is a progressive loss of mobility, and by adolescence, patients with Duchenne may require the use of a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications. For more information about Duchenne, please visit wespeakduchenne.com. About NS Pharma, Inc. NS Pharma, Inc., is a wholly owned subsidiary of Nippon Shinyaku Co., Ltd. NS Pharma is a registered trademark of the Nippon Shinyaku Co., Ltd. For more information, please visit nspharma.com. US Media Contact: [email protected] SOURCE NS Pharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果孤儿药上市批准临床研究

2024-10-05

·佰傲谷BioValley

首个细胞外泌体疗法即将提交BLA

近日，Capricor Therapeutics宣布，将于10月向美国FDA提交其在研细胞疗法Deramiocel（CAP-1002）的生物制品许可申请（BLA），用于治疗杜氏肌营养不良症（DMD）相关的心肌病。根据报道，DMD心肌病是DMD患者的主要死亡原因，目前还没有批准的DMD心肌病药物。通过外泌体介导治疗 CAP-1002是一种基于外泌体作用的异体细胞治疗，由心球衍生细胞（CDC）组成，CDC是一种源自于健康人类心脏细胞的内源性基质细胞群。 CAP-1002通过分泌外泌体来进行免疫调节、抗炎和抗纤维化，以减缓DMD疾病进展。同时，CAP-1002的外泌体中包含有microRNA等活性物质，通过这类非编码RNA，能够改变巨噬细胞和其他靶细胞的基因表达，从而抑制DMD中的全身炎症，以及刺激组织再生长。另外，相较于其他种类的细胞与基因治疗，CAP-1002不是一次性治疗药物，而是一种需要周期性给药的细胞药物。根据Capricor公司的研究显示，患者每3个月给药一次CAP-1002，每次剂量为1.5亿个细胞。目前，CAP-1002已经获得了来自FDA授予的再生医学先进疗法（RMAT）和孤儿药指定，用于治疗杜氏肌营养不良症（DMD）。 3年临床数据根据报道，CAP-1002的BLA申请将基于2期研究HOPE-2、HOPE-2开放标签扩展（HOPE-2 OLE）的数据；并与范德堡大学医学中心和辛辛那提儿童医院医学中心提供的自然历史数据进行比较。在6月早些时候，Capricor公司披露了HOPE-2 OLE的3年疗效结果，结果显示：与DMD外部数据集（由辛辛那提儿童医院医学中心(CCHMC)提供）相比，接受CAP-1002的患者在治疗3年后继续显示出积极的益处。此外，在整个研究过程中，HOPE-2-OLE研究期间CAP-1002继续表现始终如一的良好耐受安全性。来自HOPE-2 OLE研究的数据显示，多种心脏测量都有所改善，包括包括左心室射血分数（LVEF）以及左心室收缩末期容积（LVESV）和左心室舒张末期容积（LVEDV）。此外，在HOPE-2随机试验开始时，在射血分数较高（> 45%）的患者中观察到心脏功能更好的改善。 2022年3月，《柳叶刀》刊登了CAP-1002的HOPE-2研究数据。 2018年3月1日至2020年3月31日期间，26名DMD男性患者被纳入试验。其中，8名患者被随机分配到CAP-1002组，12名患者被分配到安慰剂组，6名患者因筛查失败而未被随机分配。一名随机分配到CAP-1002的患者在第3个月（第二次输注）因严重过敏反应推出。三名随机分配到安慰剂组的患者选择停药。最后安慰剂组有10名参与者，CAP-1002组有8名参与者。结果显示：与基线相比，PUL 1.2评分的平均12个月变化，CAP-1002优于安慰剂，输注CAP-1002可以减缓71%的功能丧失。中期PUL 1.2的6个月变化的次要终点在各组之间存在显著差异，CAP-1002优于安慰剂。延伸阅读：《柳叶刀》：细胞治疗能够显著延缓DMD的疾病进展此外，为了支持CAP-1002在DMD骨骼肌肌病的潜在扩展标签，Capricor公司计划将3期研究HOPE-3中的队列A和B合并作为批准后研究，目前不打算对队列A进行揭盲，预计将于2024年第四季度进行。小结值得注意的是，Capricor公司正在为支持BLA和潜在的商业化而建立内部GMP生产，包括正在扩大圣地亚哥的工厂。目前，全球市场上，用于DMD治疗的药物有多种，包括外显子跳跃疗法（Exondys 51、Vyondys 53、Amondys 45、Viltepso）、小分子药物（Ataluren、Duvyzat）、激素治疗（泼尼松、泼尼松龙、地夫可特等）、以及重磅药物AAV基因治疗Elevidys。但是，尚无针对DMD心肌病的药物获批上市。参考资料： 1.https://www.capricor.com/investors/news-events/press-releases/detail/291/capricor-therapeutics-announces-intent-to-file-biologics 2.https://www.capricor.com/investors/news-events/press-releases/detail/284/capricor-therapeutics-announces-long-term-benefit-of 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

孤儿药临床结果临床2期

2024-09-29

·药明康德

从无药可医到多款疗法获批，DMD疗法的下一步走向何方？

▎药明康德内容团队编辑在近日举办的2024药明康德投资者开放日上，药明康德联席首席执行官陈民章博士对化学业务平台能力、规模及业务增长驱动力进行了精彩分享。其中，药明康德在开发包括吗啉代反义寡核苷酸（PMO）和多肽-PMO偶联物（PPMO）在内的寡核苷酸药物方面的能力，有望为大量罕见病患者带来福音。9月恰逢肌肉萎缩症公共意识月（Muscular Dystrophy Awareness Month），在今天这篇文章中，药明康德内容团队将以杜氏肌营养不良症（DMD）为引子，介绍PMO/PPMO疗法如何为DMD患者，乃至更多罕见病患者带来了新希望。 DMD是一种致命的罕见肌肉萎缩疾病，由于编码抗肌萎缩蛋白（dystrophin）的基因发生变异，导致肌肉逐渐无力萎缩。全球范围内，大约每3500-5000名男性新生儿中就有1名DMD患儿，每年有2万名儿童确诊DMD。患者的预期寿命很少超过40岁。可喜的是，在科学家和药物研发人员的共同努力下，自2016年以来，已经有8款DMD疗法获得美国FDA的批准，其中5款创新疗法针对DMD疾病的根本原因。 ▲FDA批准治疗DMD的药物（数据来源：公开资料，药明康德内容团队制图，截至2024年9月19日）针对DMD疾病根源的新治疗模式既然DMD的产生源于抗肌萎缩蛋白的缺失，那么提高抗肌萎缩蛋白的表达，就有望恢复肌肉细胞的功能，减少肌肉细胞的损伤。已有5款利用这个作用机制的创新疗法获得了FDA的批准。其中最主要的一类是寡核苷酸疗法，包括Sarepta Therapeutics公司的Amondys 45，Vyondys 53，和Exondys 51，以及Nippon Shinyaku公司的Viltepso。它们作用机制类似，通过让寡核苷酸药物与编码抗肌萎缩蛋白的mRNA前体结合，改变mRNA前体的剪接过程，跳过携带基因突变的DMD外显子，从而生成具有大部分抗肌萎缩蛋白功能的截短蛋白。 ▲以Viltepso（又名NS-065）为例展示的寡核苷酸疗法作用机制（图片来源：Nippon Shinyaku公司官网）另一类则是基因疗法，比如罗氏与Sarepta Therapeutics联合开发的基因疗法Elevidys（delandistrogene moxeparvovec，SRP-9001）将表达微抗肌萎缩蛋白（micro-dystrophin）的转基因包装在腺相关病毒（AAV）载体中，通过单次静脉注射，使得患者肌肉生成具有部分抗肌萎缩蛋白功能的重组蛋白。与基因疗法相比，寡核苷酸疗法生成的抗肌萎缩蛋白保存了野生型蛋白中更多的结构域，能够更好地模拟野生型蛋白的功能。并且，通过改变寡核苷酸疗法的序列，可以迅速使用这一治疗模式靶向其它基因或者突变。因此，这一药物类型得到了产业相当多的关注。目前，所有4款获批的寡核苷酸疗法均采用了PMO技术，PMOs是一类基于RNA天然框架设计的合成分子。尽管PMOs含有与RNA相同的核酸碱基，它们却与六边型的吗啉环相连接，而不是与RNA中的五边型的核糖环相连。此外，这些吗啉环通过磷酰二胺键连接，而不是RNA中的磷酸二酯键。这种结构使PMOs能够与特定的mRNA前体序列结合，同时在生物体内不容易被降解。 ▲PMO结构示意图（图片来源：参考资料[1]）值得一提的是，药明康德化学业务平台的新分子板块（WuXi TIDES）于2018年布局，在多肽和寡核苷酸等新分子的开发和生产方面不断精进平台能力。以PMO为例，这类分子类型合成、生产极为复杂，药明康德基于大量知识经验的积累和洞见，不断优化工艺、内部整合流程提供一体化服务，在3年内将PMO类药物活性成分（API）成本降低60%，让这类药物成为一种可行的治疗模式。任何一种疗法都有其优势与局限，PMO疗法也不例外：它们的组织渗透能力不强，不容易被肌肉细胞吸收。即便被细胞摄取后，也很容易在溶酶体中被降解。如何提高寡核苷酸疗法的组织特异性递送，在提高疗效的同时降低剂量，并且扩展适用的疾病范围，成为这一领域的重要研发方向。现有疗法的局限性，也促使更多生物技术公司继续加大投入，开发新一代的DMD疗法，以更好地造福病患。偶联技术提高寡核苷酸疗法递送效率和表达水平为了提升PMO疗法的临床效果，各个公司处于临床阶段的寡核苷酸药物纷纷在药物合成工艺上进行了创新。其中一种方式便是将寡核苷酸与细胞穿透肽（CPP）相偶联，形成称之为PPMO的新一代PMO疗法。CPP由少于30个氨基酸组成，具有两亲性或阳离子性，能够携带大分子生物载荷穿透细胞膜，从而增加寡核苷酸的细胞和组织渗透性，这使药物在低剂量时便具有增强的疗效。此外，临床前实验结果也显示，PPMO疗法能够促进抗肌萎缩蛋白的持续生产，并可靶向横膈肌与心肌，且能以更高的效率递送至目标组织。目前，几款PPMO疗法已进入临床试验阶段。其中Sarepta Therapeutics开发的SRP-5051（vesleteplirsen）旨在与抗肌萎缩蛋白的mRNA前体外显子51结合，促使mRNA在处理过程中跳过该外显子，从而生成缩短但功能保留的抗肌萎缩蛋白。根据今年初公布的2期多剂量递增试验结果，接受该疗法的DMD患者产生了令人鼓舞的抗肌萎缩蛋白水平。 ▲抗体（左）与CPP（右）偶联寡核苷酸疗法示意图（图片来源：参考资料[5]）此外，PepGen公司通过其专有EDO平台开发的PPMO疗法PGN-EDO51也正在临床2期试验中，评估其在适合外显子51跳跃基因突变的DMD患者中的疗效与安全性。EDO平台的专有CPP可增强细胞摄取，并促使寡核苷酸在被溶酶体降解前成功逃逸。临床前研究表明，该疗法能够有效递送至多种肌肉组织，包括心肌、骨骼肌和平滑肌，展现出广泛的治疗潜力。同样为了应对溶酶体降解的挑战，Entrada Therapeutics开发了ENTR-601-44，这款疗法由该公司专有的内体逃逸载体（EEV）多肽与PMO偶联，旨在治疗适合接受外显子44跳跃疗法的DMD患者。今年6月发布的1期临床试验结果显示，与安慰剂组相比，接受ENTR-601-44治疗的患者，其外显子跳跃水平显著提高，具统计学意义。 ▲部分处于临床阶段的下一代DMD寡核苷酸疗法在研管线（数据来源：公开资料，药明康德内容团队制图，截至2024年9月19日） PMO、PPMO相关疗法的开发需要极复杂的工艺技术，而药明康德在化学业务上20年的丰富经验为开发这类新一代疗法打下坚实的基础。根据2024药明康德投资者开放日公开的信息，其团队具备PMO单体、PMO、多肽、PPMO偶联及制剂开发的综合能力，在PMO与PPMO疗法的开发上是唯一可以提供“一站式”解决方案的CDMO。投资者开放日上，我们还看到了一个具体的赋能案例：对于生产技术极为复杂的PPMO疗法，公司寡核苷酸、多肽、制剂、分析等6个团队平行推进、无缝衔接，将一款来自客户的在研疗法仅用11个月推进至IND。这也得益于药明康德在CMC一体化解决方案方面的专精与专长。截至目前，药明旗下负责PMO和PPMO生产的WuXi TIDES平台已为三款治疗DMD的PMO和PPMO疗法提供了研发赋能。值得一提的是，今年8月，PepGen公司首席执行官James McArthur在接受《波士顿商业杂志》采访时特地感谢了药明康德为其公司提供的赋能服务。这名行业老兵已经在产业里摸爬滚打了超过25年，他直言与药明康德的合作已经贯穿了他的多家公司。在先前的一家公司里，没有一家美国的供应商能在有限的时间里完成他们想要的工作，只有药明康德满足了他的要求。展望未来，考虑到寡核苷酸疗法的作用机制，此类疗法的治疗范围远不只是DMD，更多不同的罕见病患者有望从这种新分子疗法中受益。能为全球创新合作伙伴们赋能，药明康德倍感荣幸。我们也祝愿更多好药新药能够顺利问世，造福全球病患！ ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Roberts et al, (2023). Therapeutic approaches for Duchenne muscular dystrophy. Nature Reviews Drug Discovery. https://doi-org.libproxy1.nus.edu.sg/10.1038/s41573-023-00775-6 [2] MDA Kicks Off Muscular Dystrophy Awareness Month in September with ‘30 Days of Strength’ Campaign with Hundreds of Events to Advance Research and Care for the Neuromuscular Disease Community. Retrieved September 19, 2024, from https://www.mda.org/press-releases/2024/mda-kicks-off-muscular-dystrophy-awareness-month-in-september-with-30-days-of-strength-campaign-with-hundreds-of-events-to-advance-research-and-care-for-the-neuromuscular-disease-community [3] RNA Platform Leveraging RNA technology to treat rare disease. Retrieved September 19, 2024, from https://www.sarepta.com/science/rna-platform [4] Sarepta Therapeutics Corporate Presentation 2024. Retrieved September 19, 2024, from https://investorrelations.sarepta.com/static-files/54793bd6-09b6-4c68-8281-39e586071e88 [5] Roberts TC, Langer R, Wood MJA. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020 Oct;19(10):673-694. doi: 10.1038/s41573-020-0075-7. Epub 2020 Aug 11. PMID: 32782413; PMCID: PMC7419031. [6] Avidity Biosciences Announces Positive AOC 1044 Data Demonstrated Significant Increase of 25% in Dystrophin Production and Reduction of Creatine Kinase Levels to Near Normal in People Living with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping in the Phase 1/2 EXPLORE44™ Trial. Retrieved September 22, 2024 from https://www.prnewswire.com/news-releases/avidity-biosciences-announces-positive-aoc-1044-data-demonstrated-significant-increase-of-25-in-dystrophin-production-and-reduction-of-creatine-kinase-levels-to-near-normal-in-people-living-with-duchenne-muscular-dystrophy-amenab-302218647.html [7] Sarepta Therapeutics Announces Positive Data from Part B of MOMENTUM, a Phase 2 Study of SRP-5051 in Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 51. Retrieved September 22, 2024 from https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-positive-data-part-b-momentum [8] Advancing the Use of Peptide-Conjugated Oligonucleotides to Target Neuromuscular Disorders: Enhanced Delivery Oligonucleotides for DMD and DM1. Retrieved September 22, 2024 from https://investors.pepgen.com/static-files/ff601ea2-0a29-435f-82b1-c885924cfb94 [9] Watanabe N, Tone Y, Nagata T, Masuda S, Saito T, Motohashi N, Takagaki K, Aoki Y, Takeda S. Exon 44 skipping in Duchenne muscular dystrophy: NS-089/NCNP-02, a dual-targeting antisense oligonucleotide. Mol Ther Nucleic Acids. 2023 Sep 20;34:102034. doi: 10.1016/j.omtn.2023.102034. PMID: 37854955; PMCID: PMC10579524. [10] Myotonic Dystrophy Type 1 Program. Retrieved September 22, 2024 from https://www.entradatx.com/dm1 [11] Tsoumpra MK, Fukumoto S, Matsumoto T, Takeda S, Wood MJA, Aoki Y. Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases. EBioMedicine. 2019 Jul;45:630-645. doi: 10.1016/j.ebiom.2019.06.036. Epub 2019 Jun 27. PMID: 31257147; PMCID: PMC6642283. 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

寡核苷酸信使RNA基因疗法临床研究核酸药物

100 项与维托拉生相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11528	维托拉生	J05AB	DB15005

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
杜氏肌营养不良症外显子53跳跃突变	日本	Nippon Shinyaku Co., Ltd.	2020-03-25

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
杜氏肌营养不良症	申请上市	中国	Fuji Yakuhin Co., Ltd.	2021-08-10
杜氏肌营养不良症	申请上市	中国	Nippon Shinyaku Co., Ltd.	2021-08-10

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临床结果

适应症

分期

评价

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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


NCT04956289 (CTgov)	临床2期	杜氏肌营养不良症	20	Viltolarsen	餘鑰範選壓廠艱鹹鏇獵(遞襯獵鏇鏇鹽衊夢鏇願) = 網醖獵壓願憲襯淵壓廠壓夢鬱壓齋鹹鑰簾襯淵 (鬱壓窪築積顧鏇鏇鹹壓, 範繭糧鹹憲夢夢製齋鏇 ~ 憲憲範範夢壓衊顧艱網) 更多	-	2024-08-20
NCT04060199 (RACER53, Corporate Publications) 人工标引	临床3期	杜氏肌营养不良症	77	viltolarsen	構餘糧壓網壓鹽鏇壓願(壓網鹹積製襯網淵繭蓋) = there was no statistically significant difference between the viltolarsen group and the placebo group. 夢艱範窪範鹽築築餘築 (醖窪糧膚齋淵襯醖鹽繭 ) 更多	不佳	2024-05-27
				Placebo
NCT04956289 (MDA2024) 人工标引	临床2期	杜氏肌营养不良症 dystrophin mutations	20	Viltolarsen 80 mg/kg/week	築獵獵構窪積襯衊觸獵(遞糧鏇窪構鏇鑰製餘獵) = 鏇襯憲願積鹽鹽蓋壓襯壓願夢夢繭糧壓糧願鹹 (憲窪製膚壓簾壓壓蓋艱 ) 更多	积极	2024-03-03
NCT03167255 (CTgov)	临床2期	杜氏肌营养不良症	16	NS-065/NCNP-01 (NS-065/NCNP-01 40mg/kg)	獵遞膚觸願鑰選範窪衊(鬱襯醖夢築觸鑰選繭獵) = 憲齋製簾窪願繭窪壓廠窪繭憲鹽鹹齋齋顧積廠 (窪夢製鑰範構襯襯鹽糧, 膚淵選網鏇餘淵獵範衊 ~ 衊顧遞淵廠遞糧餘衊壓) 更多	-	2022-11-18
				NS-065/NCNP-01 (NS-065/NCNP-01 80mg/kg)	獵遞膚觸願鑰選範窪衊(鬱襯醖夢築觸鑰選繭獵) = 衊夢餘鏇築壓獵觸蓋膚窪繭憲鹽鹹齋齋顧積廠 (窪夢製鑰範構襯襯鹽糧, 網鑰廠餘淵願艱艱膚艱 ~ 蓋製夢選蓋窪築膚簾製) 更多
NCT03167255 (Corporate Publications) 人工标引	临床2期	杜氏肌营养不良症 Exon 53 Skipping	16	glucocorticoid treatment+Viltolarsen	築簾蓋糧鹹窪遞獵糧鹹(顧憲膚鹽艱簾襯膚廠鬱) = 觸壓憲鏇簾憲構積衊夢網膚製憲餘鹽築鑰網醖 (獵膚鬱積艱膚鹹鏇廠窪 ) 更多	积极	2022-10-24
				glucocorticoid treatment	築簾蓋糧鹹窪遞獵糧鹹(顧憲膚鹽艱簾襯膚廠鬱) = 醖鹽壓廠膚壓願鏇獵鏇網膚製憲餘鹽築鑰網醖 (獵膚鬱積艱膚鹹鏇廠窪 ) 更多
NCT02740972 (CTgov)	临床2期	杜氏肌营养不良症	16	NS-065/NCNP-01 (NS-065/NCNP-01 40mg/kg)	壓獵願鹽襯築壓繭憲餘(鹹築蓋蓋築願壓網鬱鑰) = 膚範獵廠選選鏇獵襯鬱壓積蓋顧範蓋積窪鏇鹽 (鬱襯鬱膚願簾餘壓艱淵, 築製顧淵選遞廠築膚蓋 ~ 顧鹹鏇醖膚築襯廠選襯) 更多	-	2021-07-12
				NS-065/NCNP-01 (NS-065/NCNP-01 80mg/kg)	壓獵願鹽襯築壓繭憲餘(鹹築蓋蓋築願壓網鬱鑰) = 製衊獵鏇夢鑰構築製築壓積蓋顧範蓋積窪鏇鹽 (鬱襯鬱膚願簾餘壓艱淵, 憲選網膚鏇膚鑰鏇鏇製 ~ 齋繭窪網遞選積製淵衊) 更多
Corporate Publications 人工标引	临床2期	杜氏肌营养不良症 Exon 53 Skipping	16	viltolarsen	願醖遞廠遞觸齋艱鹹糧(顧鏇鑰鏇獵網鬱構淵築) = 築壓繭遞構選淵膚憲鹹壓餘選鹽齋襯範淵製網 (築糧鬱襯壓築遞築夢獵 ) 更多	积极	2021-07-01
				historical control	願醖遞廠遞觸齋艱鹹糧(顧鏇鑰鏇獵網鬱構淵築) = 範鏇獵糧衊選醖鏇觸鹹壓餘選鹽齋襯範淵製網 (築糧鬱襯壓築遞築夢獵 ) 更多
NCT02740972 (Pubmed \| JAMA Neurol)	临床2期	肌营养不良	16	Viltolarsen 40 mg/kg	鹽醖醖築鏇廠艱夢簾鹽(鹹廠艱網壓憲觸窪構憲) = 廠糧艱憲製鑰簾遞餘鏇選餘夢膚齋鏇觸鹹鹹鬱 (壓構繭廠網積繭鏇憲簾 )	-	2020-05-26
				Viltolarsen 80 mg/kg	鹽醖醖築鏇廠艱夢簾鹽(鹹廠艱網壓憲觸窪構憲) = 壓構膚醖鹹齋範鬱簾鹽選餘夢膚齋鏇觸鹹鹹鬱 (壓構繭廠網積繭鏇憲簾 )
NCT02081625 (pubmed \| Sci Transl Med) 人工标引	临床1期	杜氏肌营养不良症 Exon 53 Skipping	10	NS-065/NCNP-01	觸鑰築醖鬱壓製繭鑰壓(餘襯窪膚鹹觸醖衊憲艱) = 範觸艱範構廠選製壓選鹽鑰蓋膚壓夢鑰構醖簾 (憲構選簾築簾鏇鹹觸壓 ) 更多	积极	2018-04-18