Commercialization Readiness Pilot (CRP) to maximize vamorolone international labeling and sales

商业化准备试点 (CRP)，以最大限度地提高瓦莫洛龙的国际标签和销售

• 批准号: 10200153
• 负责人: ERIC P. HOFFMAN
• 金额: $ 167.24万
• 依托单位: REVERAGEN BIOPHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200153
• 关键词: 2 year old; Adolescent; Adrenal Cortex Hormones; Age; Agonist; Anti-Inflammatory Agents; Area; Award; Binding; Biological Markers; Blinded; Businesses; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Country; Cushingoid habitus; Data; Development; Disease; Dose; Double-Blind Method; Drug Approval; Duchenne muscular dystrophy; Elements; Enrollment; Ensure; Ethics; Europe; European; Family; Goals; Growth; Infant; Intellectual Property; International; Label; Lead; Legal; Legal patent; Marketing; Measures; Medicine; Mineralocorticoids; Motor Skills; Mus; National Institute of Neurological Disorders and Stroke; Newborn Infant; Outcome; Patients; Pharmaceutical Preparations; Phase; Placebos; Prednisone; Preparation; Press Releases; Procedures; Process; Program Development; Property; Protocols documentation; Publishing; Quality Control; Quality of life; Readiness; Research; Safety; Sales; Site; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Steroids; System; Time; Toxic effect; Toxicology; Visit; Voice; Weight Gain; Writing; arm; boys; clinical research site; commercialization; deflazacort; design; drug efficacy; genetic corepressor; innovation; medication safety; off-label use; open label; pre-clinical; preclinical study; programs; quality assurance; receptor; recruit; research and development; response; side effect; standard of care

Abstract Vamorolone is a first-in-class dissociative steroidal drug that is being developed for Duchenne muscular dystrophy as a replacement for corticosteroid standard of care (prednisone, deflazacort) by small business ReveraGen BioPharma. ReveraGen completed first-in-patient studies with the aid of a NINDS SBIR Direct-to- Phase II award (48 DMD boys; sequential clinical trials VBP15-002, VBP15-003, VBP15-LTE, Expanded Access Protocol), and these have been published (Conklin et al. 2018; Hoffman et al. 2019). These studies showed dose-responsive improvements in all measures of motor skills, and loss of side effects (no stunting of growth, less Cushingoid and weight gain). Biomarkers have been integrated throughout the vamorolone program, providing objective readouts of drug efficacy and safety that also showed clear dose-response in these initial open label studies. A double-blind pivotal trial of 120 DMD boys (VBP15-004) is currently 40% enrolled and recruiting at 31 sites in 11 countries. This pivotal study is supported in part by a NINDS SBIR Phase IIB award and European Commission Horizons 2020 award, and includes placebo and prednisone arms. It is anticipated that the trial will be fully enrolled in late 2019 or early 2020, and last-patient last visit anticipated in Q3 2020 leading to initiation regulatory drug approval procedures in both US (FDA NDA) and Europe (EMA MAA). ReveraGen has remained a privately held small business, and this has enabled innovations in clinical trial design, use of biomarkers, and regulatory protocols. For example, ReveraGen requested the FDA consider Expanded Access Protocols for patients leaving vamorolone clinical trials, as this would reduce burden on patient families and clinical sites, while maintaining centralized safety information, and this was approved, leading to a FDA press release encouraging others to consider a similar approach. For this Commercialization Readiness Pilot (CRP) application, ReveraGen seeks support to fill key gaps identified through a formal FDA NDA gap analysis carried out in Q3 2019, and to enable worldwide drug approval thus maximizing thus enabling worldwide drug approval and maximizing market access. Technical assistance request is to both develop a global regulatory strategy, and development of a global intellectual property strategy. Support for late stage research and development activities include filling identified gaps is Design and Quality Systems Controls, and conducting a GLP juvenile toxicity study supporting labeling and prescription to the newborn period. Completing the goals of the proposed CRP would lead to worldwide commercialization of vamorolone, and set the stage for expanding vamorolone use in many other clinical disorders were corticosteroids are effective but the severe burden of side effects limits use.

抽象的 Vamorolone是一种一流的分离式类固醇药物，正在为Duchenne Muscular开发 营养不良作为替代皮质类固醇标准的护理标准（泼尼松，Deflazacort） Reveragen Biopharma。 Reveragen借助Ninds Sbir直接完成了初次的患者研究 II期奖项（48个DMD男孩；顺序临床试验VBP15-002，VBP15-003，VBP15-LTE，扩展 访问协议），并且已发表（Conklin等，2018； Hoffman等人，2019）。这些研究 显示了所有运动技能措施的剂量反应性改进和副作用的丧失（没有发育不良 生长，较少的cushingoid和体重增加）。生物标志物已整合在整个Vamorolone 计划，提供对药物疗效和安全性的客观读数，在 这些最初的开放标签研究。目前，一项120个DMD男孩（VBP15-004）的双盲关键试验为40％ 在11个国家 /地区的31个地点招募并招募。这项关键研究部分由Ninds Sbir支持 IIB阶段奖和欧洲委员会Horizo​​ns 2020奖，包括安慰剂和泼尼松 武器。预计该审判将在2019年底或2020年初进行全面注册，最后一次访问 预计在第3季度的2020年预计，在美国（FDA NDA）和 欧洲（EMA MAA）。 Reveragen仍然是一家私人企业，这已启用 临床试验设计，生物标志物的使用和监管方案的创新。例如，Reveragen 要求FDA考虑为离开Vamorolone临床试验的患者扩大访问方案，因为 在维持集中安全信息的同时，将减轻患者家庭和临床部位的负担， 这是批准的，导致FDA新闻稿鼓励其他人考虑类似的方法。为了这 Reveragen的商业化准备飞行员（CRP）应用程序寻求支持以填补确定的关键空白 通过在2019年第三季度进行的正式FDA NDA差距分析，并启用全球药物批准 最大化，从而实现全球药物批准并最大化市场获取。技术援助 要求既要制定全球监管策略，又要发展全球知识产权 战略。支持晚期研发活动的支持包括填补确定的空白是设计和 质量系统控制并进行GLP少年毒性研究，以支持标签和处方 新生儿时期。完成拟议的CRP的目标将导致全球商业化 vamorolone，并为在许多其他临床疾病中扩展瓦莫洛龙的使用奠定了基础 皮质类固醇有效，但副作用限制的严重负担使用。

项目成果

Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes.

• DOI: 10.1016/j.steroids.2018.02.010
• 发表时间: 2018-06
• 期刊: Steroids
• 影响因子: 2.7
• 作者: Hoffman EP;Riddle V;Siegler MA;Dickerson D;Backonja M;Kramer WG;Nagaraju K;Gordish-Dressman H;Damsker JM;McCall JM
• 通讯作者: McCall JM