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

杭州泰格医药技术咨询有限公司

[+1]

EUCTR2020-003653-30-ES

/ Not yet recruiting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 - Galactic-53

开始日期2021-07-26

申办/合作机构

NS Pharma, Inc.

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]

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）

2025-01-10·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Antisense oligonucleotide as novel therapies for neurogenetic disorders].

Review

作者: Fan, Liyuan

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.

2025-01-01·Advances in Therapy

Assessment of Phosphorodiamidate Morpholino Oligomer Treatment Patterns for Patients with Duchenne Muscular Dystrophy: A MarketScan Claims Analysis

Article

作者: Klimchak, Alexa C. ; Signorovitch, James ; Innis, Bryan ; Laverty, Chamindra G ; Gooch, Katherine ; Klimchak, Alexa C ; Laverty, Chamindra G.

INTRODUCTIONPhosphorodiamidate morpholino oligomers (PMOs), weight-based treatments administered weekly by intravenous infusion, are approved in the US for patients with Duchenne muscular dystrophy (DMD) amenable to certain exon skipping. Evidence regarding PMO treatment patterns in real-world settings is limited. This study used longitudinal administrative claims data to characterize PMO treatment patterns among US patients with DMD.METHODSMarketScan^® commercial and Medicaid data (January 1, 2018-December 31, 2021) were used to identify claims for PMO treatments (eteplirsen, golodirsen, viltolarsen, casimersen). The proportion of days covered (PDC), proportion with continuous PMO claims coverage (no gaps in claims ≥ 30 days), and time to subsequent PMO claims after a ≥ 30-day gap in PMO claims were described.RESULTSOne hundred thirty-three patients with ≥ 1 PMO claim were identified. Multiple codes were needed to identify PMO treatment coverage. Mean age was 14.1 years; all patients were male. Mean continuous follow-up duration was 669.3 days. Median PDC was 83.4%. Seventy-four (55.6%) patients had continuous PMO claims coverage (no ≥ 30-day gaps in claims). Of the 59 patients with ≥ 1 gap in PMO claims of ≥ 30 days, 39 had ≥ 1 subsequent PMO claim. Accounting for censoring via Kaplan-Meier analysis, 75.5% had a subsequent PMO claim within 1 year after a ≥ 30-day gap, with a median time of 64 days (including the qualifying 30 days).CONCLUSIONUnderstanding treatment patterns is important for characterizing real-world utilization of precision genetic medicines. This study observed a high PDC for PMO treatments for DMD. Most patients had continuous PMO claims coverage, and most patients with a gap in PMO claims had a subsequent PMO claim. Nonetheless, the observed persistence may have been underestimated given shortcomings of claims data and payer coverage considerations. Caution should be exercised when inferring treatment effectiveness or tolerability based on observed treatment patterns from claims data alone for weight-based, infused PMO treatments.

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

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.

项与维托拉生相关的新闻（医药）

2025-02-20

·生物制品圈

mRNA、RNAi、circRNA、ASOs：RNA 疗法的对比指南

你肯定听说过抗体、多肽，甚至 DNA 被用作治疗手段，但 RNA 呢？在这篇综述中，我们将探讨这个被一些人认为可能和单克隆抗体一样具有革命性的领域。大约 150 年前核酸被发现后的很长一段时间里，RNA 一直被认为是一种极其脆弱、容易降解的分子，因此在治疗应用方面未得到重视。然而如今，重大的技术发展让 RNA 成为了医学研究的焦点，在诸如血友病的更好治疗方案和更廉价的疫苗等令人兴奋的应用领域崭露头角。让我们一起来回顾这项技术的工作原理以及该领域的最新进展。 1.RNAi 疗法：干预疾病进程RNA 干扰（RNAi）疗法是基于一种自然过程，RNA 序列能够通过这个过程阻断 DNA 转化为蛋白质的表达。RNAi 分子会与编码特定蛋白质的信使 RNA 分子结合，并将其引导至 RNA 诱导沉默复合体（RISC），该复合体会切割信使 RNA 分子，从而使相应的蛋白质无法产生。总部位于马萨诸塞州的 RNAi 疗法公司 Alnylam 的前总裁巴里・格林曾形象地比喻：“如果厨房水龙头漏水，如今的药物就像是在拖地，而我们的疗法则是关上水龙头。” 早在 21 世纪初，科学家们就开始意识到 RNAi 的潜力，这一发现最终在 2006 年获得了诺贝尔奖。这引发了大量投资，比如默克公司以 11 亿美元收购 Sirna Therapeutics。但不久之后，多项临床试验表明这项新兴技术可能会引发严重的副作用，大多数大型制药公司都望而却步，默克公司也在十几年前以近乎收购价十分之一的价格卖掉了 Sirna。不过格林对此并不担忧。他在 2017 年表示：“大型制药公司并不是创新的可靠风向标。他们直到蛋白质和抗体市场规模达到 200 亿美元时才涉足。” 尽管 Alnylam 自身也遭遇了一些挫折，比如早期有一个候选药物因临床试验中出现 18 例死亡事件而被撤回，几年前 fitusiran 也暂停了给药，但格林相信 RNAi 疗法终会像抗体或蛋白质药物一样受到认可。目前，美国食品药品监督管理局（FDA）将在两个月内对赛诺菲的 fitusiran 是否获批做出决定。近年来，一些 RNA 疗法已获得 FDA 批准。作为 RNA 疗法领域的重要参与者，Alnylam 的药物可能是人们最先想到的。2018 年，patisiran 获批用于治疗转甲状腺素蛋白淀粉样变性（ATTR），这是一种会影响多个器官，尤其是心脏和神经的疾病。它是一种小干扰 RNA（siRNA）疗法，能够沉默产生错误折叠蛋白质并在组织中积累，进而导致 ATTR 的突变转甲状腺素蛋白（ATTR）基因。一年后，givosiran 获批用于治疗急性肝卟啉病，这是一种罕见的遗传病，会引发严重的腹痛和其他症状。由于这种疾病是由一种酶的缺陷导致其过度产生并最终积累毒素引起的，givosiran 旨在抑制这种酶的产生。如今它的商品名为 Givlaari，代表了急性肝卟啉病治疗的重大进展，显著降低了患者急性发作的频率，提高了他们的生活质量。其他 siRNA 治疗药物还包括 2020 年获批用于治疗 1 型原发性高草酸尿症（PH1）的 lumasiran，以及 2021 年获批用于降低胆固醇的 inclisiran 。2.反义寡核苷酸（ASO）RNA 疗法：修饰基因表达另一种已获得美国和欧洲监管机构批准的 RNA 疗法是反义寡核苷酸。它们通过与特定的信使 RNA 序列结合来修饰基因表达。通过改变剪接过程（一种涉及基因物质连接和去除的过程）来纠正错误的 RNA 加工，进而修饰基因表达。它们还能通过阻止信使 RNA 的表达来阻断有害蛋白质的翻译。自 1998 年第一种反义寡核苷酸药物 fomivirsen（用于治疗艾滋病患者的病毒性眼部感染）获得 FDA 批准以来，已有多种 ASO 药物上市。对于杜氏肌营养不良症患者来说，这些药物是治疗过程中的重要进展。Golodirsen，商品名为 Vyondys 53，是一种外显子跳跃剂，靶向肌营养不良蛋白基因的第 53 号外显子，该外显子的突变会导致肌肉无力。2020 年，机制与 Vyondys 53 相似的 Viltepso 也获得了 FDA 批准。最近，Qalsody（tofersen）获得监管机构批准，用于治疗由 SOD1 突变引起的肌萎缩侧索硬化症（ALS）。它旨在降低过高的 SOD1 蛋白水平，该蛋白与运动神经元损伤有关。由于 ALS 是一种无法治愈的进行性神经退行性疾病，这种疗法代表了一种全新的治疗思路。3.mRNA：蕴含无限可能尽管自 20 世纪 50 年代末克里克描述信使 RNA 在 DNA 转化为蛋白质过程中的关键作用以来，人们就已熟知这一点，但直到很久之后它才作为一种治疗产品被深入研究。 mRNA 疗法的原理很简单。将一段 mRNA 序列导入细胞后，细胞会把它当作自身的物质，用来合成其中编码的蛋白质，从而避免了在体外生产蛋白质所带来的问题。理论上，几乎任何蛋白质都可以通过这种方法合成。但在实际应用中，传统的 mRNA 应用面临两大障碍。其一，它具有很强的免疫原性；其二，能够降解 mRNA 的核糖核酸酶几乎无处不在。不过现在科学家们可以通过调整序列和对构成 mRNA 的核苷酸构建模块进行化学修饰，轻松克服这些问题。如今，这项技术在新冠疫苗领域取得了显著成果。两款知名的新冠疫苗分别是 Comirnaty 和 Spikevax，Comirnaty 在 2020 年获得紧急使用授权，并于 2021 年获得全面批准；Spikevax 则在 2022 年获得全面批准。这两款疫苗分别由辉瑞和 BioNTech、Moderna 研发，它们利用 mRNA 技术编码新冠病毒的刺突蛋白。注入人体后，mRNA 会被细胞翻译，促使刺突蛋白产生，从而刺激免疫系统产生免疫反应，使人体能够识别并对抗病毒，即便未来再次接触病毒也能发挥作用。从那以后，为了研发出高效的疫苗，许多 mRNA 疫苗在临床上进行了试验。如今，随着禽流感的传播，美国卫生部门刚刚与 Moderna 签订了一份价值 5.9 亿美元的合同，以推进 mRNA 禽流感疫苗的临床试验。此外，Moderna 的 mRESVIA 疫苗也获得了 FDA 批准，用于预防呼吸道合胞病毒（RSV）感染。虽然这项技术在疫情期间声名大噪，但它在癌症治疗研究方面也可能发挥关键作用。个性化癌症疫苗是根据患者肿瘤中存在的独特突变量身定制的。对肿瘤基因组进行测序可以识别新抗原，即肿瘤特异性的突变蛋白质。然后可以将这些新抗原编码到 mRNA 中制成疫苗。由于疫苗是个性化的，因此在杀死肿瘤细胞方面具有高度靶向性的潜力。疫苗开发商 BioNTech 在这个领域颇具潜力。其 FixVac mRNA 癌症疫苗平台的原理是激活能够识别癌症特异性抗原的免疫细胞来对抗癌细胞。去年，该平台的一个候选疫苗在 2 期临床试验中取得成功，晚期黑色素瘤患者的总体缓解率（ORR）有了统计学上的显著提高。Moderna、Gritstone Bio 和 CureVac 也备受关注，它们都在推进各自的 mRNA 候选产品进入临床试验，用于治疗实体瘤和血液癌症。然而，这项技术并非没有挑战，其中主要与递送有关。mRNA 疗法的一个主要障碍是如何在正确的时间将 mRNA 输送到正确的细胞中。mRNA 是一种大的带负电荷的分子，不容易自然穿过细胞。脂质纳米颗粒（LNPs）是目前将 mRNA 输送到细胞中最常用的方法，但设计出既有效又安全的 LNPs 仍是一个持续研究的领域。此外，mRNA 疫苗生产成本高昂，需要冷链储存，运输也比较困难，这使得将疫苗送达患者手中的整个过程变得复杂。在这方面，环状 RNA（circRNA）可能会有所作为。事实上，有传言称它甚至可能取代 mRNA，因为其生产成本可能更低，且稳定性更高。4.环状 RNA 疗法：会取代 mRNA 技术吗？环状 RNA 本质上是一种单链 RNA 分子，具有闭环结构，不编码任何蛋白质。1991 年它刚被发现时，曾被认为是错误产物而遭到忽视。但时代已经不同了。挪威生物技术公司 Circio 是该领域的先驱。其 circVec 平台是一种基因盒，旨在细胞内产生 circRNA。它可以针对任何 DNA 或病毒载体进行定制，通过 circRNA 实现蛋白质表达。其首个候选产品旨在治疗 α - 1 抗胰蛋白酶（AAT）缺乏症患者，这是一种罕见的遗传病，可能导致肺部或肝脏疾病。总部位于马萨诸塞州的 Orna Therapeutics 自 2021 年凭借 1 亿美元的资金首次亮相以来，在该领域的地位不断巩固。它正在开发由线性 RNA 前体形成的环状 RNA 技术平台 oRNA。去年，它收购了同为环状 RNA 开发商的 ReNAgade Therapeutics，并且正在创建一种可扩展的 LNP 递送系统。该公司的两个平台分别是 panCAR（能够同时靶向免疫系统的多个谱系）和 SiTu Editing in the Marrow（STEM，靶向骨髓中的干细胞）。很快，随着像 Orna 这样的年轻生物技术公司专注于治疗癌症、自身免疫性疾病和某些遗传疾病，科学家们的目标是将这项技术推向临床应用。5.RNA 疗法的未来发展方向目前，RNA 疗法在各种疾病治疗领域都是热门话题。mRNA 在疫情期间的影响力为其在传染病预防方面的更广泛应用打开了大门。除了呼吸道合胞病毒和流感，生物制药公司正在推进针对寨卡病毒和疟疾的候选疫苗研发。Moderna 的 2 期候选疫苗 mRNA - 1893 包含编码寨卡病毒结构蛋白的 mRNA 序列，旨在使细胞分泌病毒样颗粒，模拟细胞在自然感染后的反应。然而，由于去年该公司宣布如果无法获得资金就将停止试验，这款疫苗的前景堪忧。与此同时，遗传和罕见疾病也受到了应有的关注。针对肺部疾病囊性纤维化，福泰制药（Vertex Pharmaceuticals）有一种 mRNA 药物，该药物在近三年前获得了新药研究申请（IND）批准。针对镰状细胞病和 β - 地中海贫血这两种遗传性血液疾病的试验也在进行中。宾夕法尼亚大学佩雷尔曼医学院的 mRNA 基因疗法取得了显著进展，它可以在人体细胞内纠正导致镰状细胞病的基因突变，而无需在体外对细胞进行改造。根据 2023 年发表的一篇概念验证论文，研究人员表示该疗法可以通过脂质纳米颗粒（LNP）递送，这将降低成本并提高基因疗法的可及性。不仅如此，RNA 技术还有望改变自身免疫性疾病患者的治疗现状。许多自身免疫性疾病患者依赖免疫抑制剂治疗，但免疫抑制剂会增加感染风险。通过改变免疫细胞的行为，RNA 有可能提供一种更具针对性的治疗方法。百时美施贵宝（Bristol Myers Squibb）和 Repertoire Immune Medicines 去年达成了一项价值高达 18 亿美元的合作协议，旨在开发用于 “重置免疫系统” 的耐受性 mRNA 疫苗。目前该项目正处于挑选用于治疗自身免疫性疾病候选疫苗的阶段。随着 mRNA 疗法的迅速成功和 RNAi 技术的持续突破，RNA 疗法领域充满了潜力。尽管在递送等方面仍然存在挑战，但研发的步伐只会越来越快，研究人员正致力于开发可扩展的方法，为数百万人带来有效的治疗方案。参考来源：RNA therapeutics: A comparative guide 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观，不代表本站立。

siRNA并购信使RNA临床2期核酸药物

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

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	临床2期	中国	Nippon Shinyaku Co., Ltd.	2021-08-10
杜氏肌营养不良症	临床2期	中国	Fuji Yakuhin Co., Ltd.	2021-08-10

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04060199 (RACER53, CTgov)	临床3期	杜氏肌营养不良症	77	Viltolarsen (Viltolarsen)	鏇壓鏇齋衊襯鏇淵範繭(廠願衊構膚觸範構觸艱) = 衊廠蓋遞觸蓋選顧醖壓鹹繭艱蓋築膚遞鑰蓋觸 (淵簾範壓夢築衊膚積製, 膚艱簾繭艱製簾獵構範 ~ 繭憲構範獵觸蓋糧衊簾) 更多	-	2024-12-11
				Placebo (Placebo)	鏇壓鏇齋衊襯鏇淵範繭(廠願衊構膚觸範構觸艱) = 齋壓構獵鹹遞築衊蓋餘鹹繭艱蓋築膚遞鑰蓋觸 (淵簾範壓夢築衊膚積製, 醖蓋製顧獵積蓋遞築衊 ~ 鹽鏇築範構衊築齋顧網) 更多
NCT04956289 (CTgov)	临床2期	杜氏肌营养不良症	20	Viltolarsen	簾顧鑰簾積糧襯衊積糧(膚淵觸觸製壓壓鹽獵簾) = 觸觸鬱築襯積觸襯構願鑰範鬱範鹹餘壓積憲鑰 (網選壓窪鏇構窪製齋膚, 蓋壓觸襯願網鹹網願觸 ~ 顧網夢鬱齋壓獵鑰蓋壓) 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	(觸鹹襯糧鹽夢觸鏇築餘) = there was no statistically significant difference between the viltolarsen group and the placebo group. 蓋艱鏇築淵鏇積襯憲繭 (築積衊夢憲廠餘繭衊積 ) 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	(憲鏇構觸願選網觸窪鬱) = 鏇願襯鬱糧糧壓積艱衊範廠獵繭壓顧襯窪繭繭 (艱齋齋衊觸糧積壓醖獵 ) 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)	廠繭製繭範顧觸願鑰衊(膚鹹廠鑰範夢範鹽襯鹹) = 網憲獵網構鏇衊積鹹簾壓繭積獵憲膚獵製簾鑰 (醖鬱夢膚膚艱願淵顧願, 衊選簾壓願壓夢鹹選簾 ~ 繭艱廠醖簾構願簾觸醖) 更多	-	2022-11-18
				NS-065/NCNP-01 (NS-065/NCNP-01 80mg/kg)	廠繭製繭範顧觸願鑰衊(膚鹹廠鑰範夢範鹽襯鹹) = 積築願築憲築齋鬱醖顧壓繭積獵憲膚獵製簾鑰 (醖鬱夢膚膚艱願淵顧願, 簾壓選廠鑰獵壓壓鹽蓋 ~ 選築繭網襯廠範襯遞願) 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	(膚鬱淵選壓網範簾餘廠) = 衊簾選衊遞衊餘簾繭鑰顧願蓋鏇觸製遞積憲憲 (餘鑰鹹簾蓋鏇鬱壓構鹹 ) 更多	积极	2022-10-24
				glucocorticoid treatment	(膚鬱淵選壓網範簾餘廠) = 壓鹽構糧網選鹽憲觸繭顧願蓋鏇觸製遞積憲憲 (餘鑰鹹簾蓋鏇鬱壓構鹹 ) 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)	繭繭構淵糧獵齋製齋艱(憲觸襯遞選齋艱艱鹹淵) = 蓋蓋觸齋糧範鑰鹹淵繭鑰選醖構選壓鹹衊襯築 (顧獵範壓壓觸積衊築構, 蓋夢願構製衊淵壓窪憲 ~ 鬱繭醖願鑰網網繭衊憲) 更多	-	2021-07-12
				NS-065/NCNP-01 (NS-065/NCNP-01 80mg/kg)	繭繭構淵糧獵齋製齋艱(憲觸襯遞選齋艱艱鹹淵) = 簾餘衊鹽夢夢鹽繭網觸鑰選醖構選壓鹹衊襯築 (顧獵範壓壓觸積衊築構, 廠壓鑰艱鹽膚壓願廠餘 ~ 網憲鑰鏇淵築鏇網艱膚) 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	(範願襯遞獵範廠繭齋廠) = 艱憲襯廠窪窪鬱淵膚鹽簾壓齋廠壓鑰觸餘衊網 (鬱製鑰繭窪選蓋簾遞蓋 ) 更多	积极	2021-07-01
				historical control	(範願襯遞獵範廠繭齋廠) = 醖餘蓋繭顧築醖繭壓製簾壓齋廠壓鑰觸餘衊網 (鬱製鑰繭窪選蓋簾遞蓋 ) 更多
NCT02740972 (Pubmed \| JAMA Neurol)	临床2期	肌营养不良	16	Viltolarsen 40 mg/kg	淵構襯衊構繭鑰構壓淵(襯廠獵壓鹽壓選繭壓築) = 壓網齋齋觸願醖構遞艱積襯獵齋壓齋製膚選範 (壓齋鏇糧衊壓壓鬱鹹鏇 )	-	2020-05-26
				Viltolarsen 80 mg/kg	淵構襯衊構繭鑰構壓淵(襯廠獵壓鹽壓選繭壓築) = 築窪憲鑰鏇構憲獵鹽簾積襯獵齋壓齋製膚選範 (壓齋鏇糧衊壓壓鬱鹹鏇 )
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	(觸顧鑰獵築繭窪衊淵繭) = 窪鑰蓋選遞壓範鹽願繭積糧餘襯築衊鏇憲艱鹹 (範窪膚願網網簾襯齋網 ) 更多	积极	2018-04-18