A Phase 1/2, Multicenter, Open-Label Study to Investigate the Safety, Tolerability, and Efficacy of a Single Intravenous Dose of SGT-003 in Ambulant Males With Duchenne Muscular Dystrophy (INSPIRE DUCHENNE)

This is a multicenter, open-label, non-randomized study to investigate the safety, tolerability, and efficacy of a single intravenous (IV) infusion of SGT-003 in participants with Duchenne muscular dystrophy. There will be 2 cohorts in this study. Cohort 1 will include participants 4 to <7 years of age. Cohort 2 will include participants 7 to <12 years of age. All participants will receive SGT-003 and will be enrolled in the study for 5 total years for long-term follow up.

开始日期2024-05-06

申办/合作机构

Solid Biosciences, Inc.

NCT05657938 / CompletedN/A

A Phase 0 Study to Evaluate the Clinical Readiness of a Wearable Sensor Device and Duchenne Video Assessment in the Home Environment on Participants With Duchenne Muscular Dystrophy (DMD)

This study is designed to evaluate the feasibility, wearability and participant satisfaction of novel outcome assessment tools in DMD patients which are performed in the home environment.

开始日期2022-10-13

申办/合作机构

Solid Biosciences, Inc.

NCT03680365 / CompletedN/A

Your Voice; Impact of DMD. A Qualitative Assessment of the Impact of DMD on the Lives of Families

The purpose of this study is to improve the understanding of the treatment goals that a person with Duchenne Muscular Dystrophy (DMD) or the caregiver may be most interested in, based on the severity of the person's disease. Data will be collected by online survey when the participant accepts the study invitation ("RSVP questionnaire") and telephone interview on the functional burden and self-identified treatment goals from the perspective of people with DMD and their caregivers. Interviews will be analyzed to help identify things important to Duchenne families to measure in clinical trials and to inform the selection of key concepts of interest and development of future clinical outcome measures, including observer reported outcomes/patient reported outcomes. The study will be conducted in the United States and will enroll between 45 and 120 participants 11 years or older living with DMD as well as their caregivers. The time commitment for the online survey and the telephone interview is about one hour. It is anticipated that the entire study will be completed within one year.

开始日期2018-09-20

申办/合作机构

Pfizer Inc.

[+11]

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0 项与 Solid Biosciences, Inc. 相关的专利（医药）

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项与 Solid Biosciences, Inc. 相关的文献（医药）

2024-09-03·Journal of Neuromuscular Diseases

Clinician Perspectives of Gene Therapy as a Treatment Option for Duchenne Muscular Dystrophy

Article

作者: Fernandez, Vivian ; Peay, Holly ; Mansfield, Carol ; Heslop, Emma ; Bateman-House, Alison ; Johnson, Alexandra ; Donisa-Dreghici, Roxana ; McNiff, Megan ; Phillips, Dawn ; Thakrar, Sejal ; Fischer, Ryan ; Beaverson, Katherine L. ; Camino, Eric ; Cope, Heidi ; Ganot, Annie ; Denger, Brian ; Armstrong, Niki ; Woollacott, Ione O.C.

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies. Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied. Methods: We conducted interviews with specialist clinicians treating patients with DMD in the United States (n = 8) and United Kingdom (n = 8). Interviews were completed in 2022, before any approved gene therapies, to gain insight into barriers and facilitators to implementing gene therapy and educational needs of clinicians. Results: Most respondents expressed cautious optimism about gene therapy. Responses varied regarding potential benefits with most expecting delayed progression and duration of benefit (1 year to lifelong). Concern about anticipated risks also varied; types of anticipated risks included immunological reactions, liver toxicity, and cardiac or renal dysfunction. Clinicians generally, but not uniformly, understood that gene therapy for DMD would not be curative. Most reported needing demonstrable clinical benefit to justify treatment-related risks. Conclusions: Our data demonstrate variability in knowledge and attitudes about gene therapy among clinicians who follow patients with DMD. As our knowledge base about DMD gene therapy grows, clinician education is vital to ensuring that accurate information is communicated to patients and families.

2023-08-01·Rheumatology (Oxford, England)

A novel estrogen receptor 1: sphingomyelin phosphodiesterase acid-like 3B pathway mediates rituximab response in myositis patients

Article

作者: Kendra, Ryan M ; Hoffman, Eric P ; Boehler, Jessica F ; Rider, Lisa G ; Miller, Frederick W ; Peterson, Jennifer M ; O’Hanlon, Terrance P ; Li, Ning ; Parkes, Joanna E ; Nagaraju, Kanneboyina

Abstract:

Objectives:

The B-cell depleting biologic, rituximab, is used to treat refractory autoimmune myositis. However, the beneficial effects of rituximab appear to outweigh the known contribution of B cells in myositis. We aimed to elucidate how myositis patients respond differently to rituximab and possible alternative mechanisms of action.

Methods:

Here we have: (i) comprehensively investigated concurrent mRNA and microRNA expression in muscle biopsies taken at baseline and 16 weeks post treatment in 10 patients who were part of the rituximab in myositis (RIM) trial; and (ii) investigated the beneficial effect of rituximab on myositis muscle cells.

Results:

Our analyses identified an increased number of changes in gene expression in biopsies from patients who had a clinical response to rituximab (n = 5) compared with non-responders (n = 5). The two groups had completely different changes in microRNA and mRNA expression following rituximab therapy, with the exception of one mRNA, BHMT2. Networks of mRNA and microRNA with opposite direction of expression changes highlighted ESR1 as upregulated in responders. We confirmed ESR1 upregulation upon rituximab treatment of immortalized myotubes and primary human dermatomyositis muscle cells in vitro, demonstrating a direct effect of rituximab on muscle cells. Notably, despite showing a response to rituximab, human dermatomyositis primary muscle cells did not express the rituximab target, CD20. However, these cells expressed a possible alternative target of rituximab, sphingomyelinase-like phosphodiesterase 3 b (SMPDL3B).

Conclusion:

In addition to B-cell depletion, rituximab may be beneficial in myositis due to increased ESR1 signalling mediated by rituximab binding to SMPDL3B on skeletal muscle cells.

2023-05-01·Human gene therapy

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials

Article

作者: McDonald, Craig ; Duan, Dongsheng ; Morris, Carl ; Brown, Kristy J. ; Chamberlain, Jeffrey S. ; Ganot, Annie ; Wagner, Kathryn R. ; Hunter, Nina ; Tobolowsky, Mark ; Ziolkowski, Olivia ; Braun, Serge ; Gonzalez-Alegre, Pedro ; Robb, Melissa ; Danos, Olivier

Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the DMD gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs. The adeno-associated virus (AAV) vector is the leading gene delivery system for addressing genetic neuromuscular diseases. Since the gene encoding the full-length dystrophin protein exceeds the packaging capacity of a single AAV vector, gene replacement therapy based on AAV-delivery of shortened, yet, functional microdystrophin genes has emerged as a promising treatment. This article seeks to explain the rationale for use of the accelerated approval pathway to advance AAV microdystrophin gene therapy for DMD. Specifically, we provide support for the use of microdystrophin expression as a surrogate endpoint that could be used in clinical trials to support accelerated approval.

123

项与 Solid Biosciences, Inc. 相关的新闻（医药）

2024-10-27

·微信

辉瑞DMD基因疗法折戟，试验结果“打脸”FDA

来源：药渡撰文：哥哈骎编辑：维他命在基因治疗领域，监管决策的每一次松动都可能对未来的治疗标准和患者的治疗方案产生深远影响。FDA的CBER主任Peter Marks在批准Sarepta Therapeutics的杜氏肌营养不良症（DMD）基因疗法Elevidys时，采取了相对宽松的尺度。这一决定不仅在FDA内部引发了争议，也为其他公司在开发和审批新疗法时带来了复杂的挑战。随着时间的推移，这种宽松的审批标准逐渐显现出其潜在的风险和影响，使得监管机构在面对新疗法时陷入进退两难的境地。如今辉瑞的DMD临床数据出炉，将新的难题摆在了FDA面前。 01 临床失败导致项目终止辉瑞的这款DMD基因疗法是fordadistrogene movaparvovec。今年8月，辉瑞宣布其III期试验 (NCT04281485) 失败并终止了这一项目，此前一名患者在II期研究中死亡。辉瑞DMD基因疗法的临床试验令整个DMD领域感到惊讶，也必然令Elevidys获批时所造成的巨大争议“前度刘郎今又来”，使得后来者的监管批准面临非常复杂的局面。虽然从科学角度来看，fordadistrogene movaparvovec发挥了应有的作用。在III期临床试验中接受该疗法的男孩产生了大量微型抗肌萎缩蛋白（Microdystrophin）。理论上，这种结果应该有助于减缓DMD。然而，参与者根本没有受益，多项肌肉功能测试的结果与安慰剂相比没有改善。 10月12日，在捷克布拉格召开的第29届世界肌肉学会国际年会上公布了此试验结果，立即在DMD领域引发了轩然大波。虽然辉瑞此前已经做出了终止该项目的决定，然而尴尬的是，Sarepta的Elevidys当初引发巨大争议的加速批准依靠的就是微型抗肌萎缩蛋白这一生物标志物，而且目前仍然有多家制药公司开发DMD疗法，微型抗肌萎缩蛋白仍然是他们仰仗的临床终点。 02 辉瑞DMD疗法失败背后的博弈辉瑞壮志未酬的DMD疗法再次将微型抗肌萎缩蛋白是否适合作为DMD疗法开发的生物标志物推到了争论的风口浪尖之上。医药界原本就对FDA凭借微型抗肌萎缩蛋白加速批准DMD疗法颇有微词，辉瑞失败的临床研究再次为反对者提供了有利的背书。微型抗肌萎缩蛋白最初是在20世纪90年代设计的，因为完整的抗肌萎缩蛋白“本尊”对应的基因体量太大，无法装载入基因治疗的递送病毒中。科学家们因此退而求其次地衍生出了缩小版的微型抗肌萎缩蛋白作为管理DMD的手段。开发者认为，微型抗肌萎缩蛋白能够保留抗肌萎缩蛋白的关键功能，因此可以移花接木地用于DMD基因疗法开发。 Sarapta的DMD基因疗法Elevidys当年凭借加速批准的途径上位，依靠的就是微型抗肌萎缩蛋白作为生物标志物，然而Sarepta当时进行的唯一随机试验却失败了。FDA的审查人员原本甚至连Sarepta的BLA申请都不愿意接受，但CBER主任Peter Marks几乎依靠一己之力就否决了手下的决定，并且有些令人惊讶地加速批准了Elevidys。这个决定也同时表明，FDA接受微型抗肌萎缩蛋白作为加速批准的生物标志物，辅以一些肌肉功能改善的数据，而不是完整的随机III期试验。值得注意的是，加速上市后的Elevidys在上市后验证性III期试验中并未达到主要终点，但次要终点得以实现。Peter Marks再次力排众议，将Elevidys的加速批准升级为标准批准，标签几乎扩大到所有患者范围。就在Elevidys的争议声在话题不断的医药开发领域中几乎要消失的时候，辉瑞的DMD疗法的失败又将问题呈现在世人面前。世界肌肉学会国际年会上公布的数据显示，使用辉瑞基因疗法fordadistrogene movaparvovec的男孩产生了几乎同健康人群数量相差无几的微型抗肌萎缩蛋白（健康人群体内生成的是完整的抗肌萎缩蛋白），然而他们的肌肉能力并没有得到任何益处。公布这一结果的伦敦大学学院儿科神经病学主任Francesco Muntoni甚至表示，他宁愿结果是没有产生微型抗肌萎缩蛋白，这样更容易解释结果。罗彻斯特大学医学中心的神经学家Emma Ciafaloni表示，FDA应该重新审视是否应该将微型抗肌萎缩蛋白作为合理的生物标志物。风口浪尖上的FDA拒绝了对辉瑞的数据发表评论。但FDA使用外交辞令表示，每种医疗产品都是独一无二的，微型抗肌萎缩蛋白是否可以作为生物标志物用于加速批准，需要具体问题具体分析。前FDA高级官员Wilson Bryan曾经对微型抗肌萎缩蛋白作为生物标志物的做法表示怀疑，如今得到了辉瑞数据的支持后，他再次表示，依靠这些衍生基因的水平不能可靠地预测DMD的临床益处。不仅是微型抗肌萎缩蛋白是否合适这个基本点，就连生产、表征和测量这种蛋白上的差异也使得这个问题更加复杂。每个微型抗肌萎缩蛋白都有差异，DMD领域对这些差异与疗效相关性存在争议。然而先河一开就很难完全关闭，目前多家制药公司仍在凭借微型抗肌萎缩蛋白试图通过加速批准入市。例如Solid Bio的首席执行官Bo Cumbo就表示，他们没有改变寻求加速批准的计划。Cumbo称，“无论如何，FDA已经承认微型抗肌萎缩蛋白是生物标志物。Sarepta就是依靠这个获批的。”Solid目前正在美国进行一项为期18个月的单组试验，主要针对年龄较大但仍能走动的男孩。正如Cumbo透露的，Solid Bio计划根据微型抗肌萎缩蛋白水平和一些临床数据寻求FDA的加速批准。Solid还将在美国以外开展一项随机试验，以期获得更广泛的批准。对于辉瑞失败的临床数据和对生物标志物有效性的挑战，Cumbo从辉瑞对微型抗肌萎缩蛋白的测量方式提出了质疑。目前尚没有确定放之四海而皆准的抗肌萎缩蛋白水平测量手段。辉瑞使用液相色谱的方法，Sarepta使用的则是western blot。Cumbo指出，辉瑞III期临床试验中的微型抗肌萎缩蛋白水平明显高于临床I期的数据，而辉瑞在III期招募的患者的抗肌萎缩蛋白水平也高于标准DMD患者的平均水平。Cumbo表示，他相信Sarepta和辉瑞的药物确实有效，但需要进行更长时间的研究，并在合适的患者身上进行研究，这有助于帮助研究人员清楚地了解微型抗肌萎缩蛋白如何减缓肌肉功能下降。 RegenxBio的DMD基因疗法开发同样也瞄准了微型抗肌萎缩蛋白这一生物标志物，他们也在FDA之前决策的加持下“不改初衷”，坚持以此作为加速批准的基石。与Solid Bio一样，RegenxBio打算在其监管提交文件中采取微型抗肌萎缩蛋白加运动功能数据的策略。虽然几乎所有专家都认为辉瑞失败的基因疗法不会迫使FDA躬身自省地反思对Elevidys的完全审批决定，但目前医生对于Elevidys的接受度不高也是事实，主要是因为其益处不够明显，而且还是一款一针几百万美元的基因疗法，面对的是“开弓没有回头箭”的局面。辉瑞的数据造成的最主要影响，是行业对于微型抗肌萎缩蛋白作为DMD加速批准的生物标志物的合理性，以及FDA在批准DMD基因疗法时对于临床设计和终点设定以及评估方面的重新审视。对于微型抗肌萎缩蛋白的怀疑扩大将是必然的趋势。今年7月发表在Nature上的一篇文章介绍了将完整抗肌萎缩蛋白基因通过一种新病毒注入患者体内的设计，或许代表着DMD疗法开发未来的方向。 03 反思与展望辉瑞的杜氏肌营养不良（DMD）基因疗法临床试验失败不仅引发了行业的广泛关注，也让人们重新思考以微型抗肌萎缩蛋白作为疗效标志物的局限性。虽然FDA在批准Sarepta的Elevidys时基于微型抗肌萎缩蛋白的生成展现了相对宽松的态度，但随着辉瑞的失败，业内对这一审批策略提出了更多质疑。对于复杂的遗传疾病如DMD，微型抗肌萎缩蛋白的生成确实显示出一定的生物学效应，但其与实际临床疗效的关系却并不明确。这次失败表明，依赖尚未充分验证的生物标志物来推动加速批准，可能导致疗法无法实现预期的长期临床益处。 FDA近年来对一些罕见病疗法，特别是基于生物标志物的加速批准，采取了较为灵活的政策。这一做法初衷良好，为治疗选择有限的罕见病患者提供更快的药物上市渠道。然而，这种政策也带来了潜在风险。生物标志物的使用虽然能够提供早期疗效的指示，但它们可能无法充分代表疗法的实际临床效果或患者的长期获益。 Elevidys的批准就是这种宽松政策的体现。FDA基于微型抗肌萎缩蛋白作为生物标志物，快速推动了这一DMD疗法的上市，这一决定在当时反映了监管机构对满足罕见病治疗需求的迫切性。然而，辉瑞此次试验的失败再次揭示出，这样的妥协可能导致疗效尚不明确的疗法进入市场，不仅可能增加患者的经济负担，也有可能降低公众对新疗法的信任度。未来，FDA和其他监管机构或将需要重新审视目前在罕见病领域的审批策略。尽管罕见病患者急需新药物，政策灵活性对于推动疗法的早期开发和上市至关重要，但药物的长期安全性和临床有效性不应因加速上市的需求而被弱化。监管机构需要在加速审批与充分验证之间找到更合理的平衡点，确保新疗法能够真正改善患者的生存质量和预后。在DMD基因疗法的未来开发中，完整抗肌萎缩蛋白基因的递送或许将成为新的方向。相比微型抗肌萎缩蛋白，完整基因的引入更接近人体自然生理状态，可能为患者提供更长效和更显著的疗效。一些研究团队已经开始尝试通过创新的基因递送技术来实现这一目标，这有望成为DMD治疗领域未来的重要突破。辉瑞DMD疗法的失败为整个行业提供了重要的反思机会，显示出主要依靠生物标志物的加速审批模式存在的局限。生物标志物仍然是药物开发的重要工具，但它们必须与恰当的临床终点相结合，才能真正推动有效疗法的开发。未来，FDA可能需要在审批过程中更多依赖随机对照试验的结果，并加强对疗效和安全性长期观察的要求，确保新药不仅带来生物学上的作用，还能为患者的生活质量带来切实的提升。参考文献： 1.Tasfaout, H. et al. Split intein-mediated protein trans-splicing to express large dystrophins. Nature 632, 192–200 (2024). https://doi.org/10.1038/s41586-024-07710-8 2.Mast, J. et al. Perplexing results from Duchenne muscular dystrophy trial raise questions about gene therapies. STAT. 21. 10. 2024. 3.Wave’s stock swells as it eyes approval following Phase II DMD victory. Clinical Trials Arena. 25. 09. 2024. 专栏作者哥哈骎南开大学本科、硕士，德国比勒菲尔德大学博士。多肽化学、多肽API GMP生产专家、欧洲制药公司首席科学家；拥有Lean Six Sigma黑带认证；著有专著《Side Reactions in Peptide Synthesis》。 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 2025版《中国药典》收官在即，药包材标准体系最新动向盘点年薪3亿美元不是梦？生物科技与制药CEO年收入调查（附2024年行业收入报告）深度盘点：5种Biotech转型之路

基因疗法加速审批

2024-09-23

·GlobeNewswire-Health Care

Solid Biosciences to Participate at Chardan’s 8th Annual Genetic Medicines Conference

CHARLESTOWN, Mass., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB) (the “Company” or “Solid”), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced that Bo Cumbo, President and CEO, and Gabriel Brooks, M.D., Chief Medical Officer, will participate in a fireside chat at Chardan’s 8th Annual Genetic Medicines Conference on Monday, September 30, 2024, at 11:00 am ET. A live webcast of the fireside chat will be available on the Events page of the Investors section of the Company website or by clicking here. A webcast replay will be archived for 30 days on the Events page. Institutional investors interested in meeting with management during the conferences may reach out to their Chardan representatives. About Solid BiosciencesSolid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit www.solidbio.com. Solid Biosciences Investor Contact:Nicole AndersonDirector, Investor Relations and Corporate CommunicationsSolid Biosciences Inc.investors@solidbio.com Media Contact:Glenn SilverFINN Partnersglenn.silver@finnpartners.com

基因疗法

2024-09-12

·GlobeNewswire-Health Care

Solid Biosciences to Participate at the 2024 Cantor Global Healthcare Conference

CHARLESTOWN, Mass., Sept. 12, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB) (the “Company” or “Solid”), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced that Bo Cumbo, President and CEO, and Gabriel Brooks, M.D., Chief Medical Officer, will participate in a fireside chat at the 2024 Cantor Global Healthcare Conference on Wednesday, September 18, 2024, at 10:20 am ET. A live webcast of the fireside chat will be available on the Events page of the Investors section of the Company website or by clicking here. A webcast replay will be archived for 30 days on the Events page. Institutional investors interested in meeting with management during the conferences may reach out to their Cantor Fitzgerald representatives. About Solid BiosciencesSolid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit www.solidbio.com. Solid Biosciences Investor Contact:Nicole AndersonDirector, Investor Relations and Corporate CommunicationsSolid Biosciences Inc.investors@solidbio.com Media Contact:Glenn SilverFINN Partnersglenn.silver@finnpartners.com

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100 项与 Solid Biosciences, Inc. 相关的药物交易

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100 项与 Solid Biosciences, Inc. 相关的转化医学

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药物(靶点)	适应症	全球最高研发状态

SGT-001 ( micro-dystrophin )	杜氏肌营养不良症更多	临床1/2期
SGT-003 ( micro-dystrophin )	杜氏肌营养不良症更多	临床1/2期
AVB-202 ( FXN )	Friedreich共济失调更多	临床前
FXN gene therapy (AavantiBio/Catalent Cell & Gene Therapy) ( FXN )	Friedreich共济失调更多	临床前
UX-810 ( dystrophin )	杜氏肌营养不良症更多	临床前