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.

摘要 Vamorolone是一种一流的解离类固醇药物，正在开发中，用于Duchenne肌肉 营养不良替代小企业使用的皮质类固醇标准治疗(强的松、地卡西酮) ReveraGen BioPharma。ReveraGen在NINDS SBIR Direct-to-to-TO的帮助下完成了首发患者研究 第二阶段奖(48名DMD男孩；序贯临床试验VBP15-002、VBP15-003、VBP15-LTE，扩大 访问协议)，并已出版(Conklin等人。2018年；霍夫曼等人。2019年)。这些研究 在运动技能的所有测量中显示出剂量反应的改善，并减少了副作用(没有发育迟缓 生长，减少库欣金和体重增加)。生物标志物已经整合到整个吸血鬼龙中 计划，提供药物有效性和安全性的客观读数，也显示出明显的剂量反应 这些最初的开放标签研究。一项对120名DMD男孩(VBP15-004)进行的双盲关键试验目前为40% 在11个国家和地区的31个地点注册和招聘。这项关键研究部分得到了NINDS SBIR的支持 IIB阶段奖和欧盟委员会2020年地平线奖，包括安慰剂和泼尼松 手臂。预计试验将在2019年底或2020年初全面登记，最后一名患者最后一次就诊 预计2020年第3季度将在美国和美国启动药品监管审批程序(FDA NDA) 欧洲(EMA MAA)。ReveraGen一直是一家私人持股的小企业，这使得 在临床试验设计、生物标记物的使用和监管方案方面的创新。例如，ReveraGen 要求FDA考虑扩大对离开万宝龙临床试验的患者的准入方案，因为这 将减轻患者家属和临床站点的负担，同时维护集中的安全信息，以及 这一做法得到了批准，导致FDA发布了一份新闻稿，鼓励其他人考虑类似的方法。为了这个 商业化准备试点(CRP)应用程序，ReveraGen寻求支持以填补已确定的关键差距 通过FDA在2019年第三季度进行的正式NDA差距分析，从而使全球药品获得批准 从而最大限度地实现全球药品审批和最大限度的市场准入。技术援助 要求既要制定全球监管战略，又要发展全球知识产权 策略。对后期研究和开发活动的支持，包括填补已确定的差距，包括IS设计和 质量体系控制，并进行GLP青少年毒性研究，支持标签和处方 新生儿期。完成拟议的CRP的目标将导致全球范围的商业化 并为扩大在许多其他临床疾病中的使用奠定了基础 皮质类固醇是有效的，但严重的副作用负担限制了使用。

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