Elamipretide Hydrochloride

一般而言，FDA专家会投票赞成批准的药品，FDA最终会批准其上市，然而，最近Stealth BioTherapeutics公司却遇到了麻烦，2024年10月，FDA专家顾问委员会明明以10比6的投票结果支持批准该公司罕见病药物elamipretide，但优先审评带来的审批加速并没有带来“上市”的结果，反而让公司收到了完整回复函（CRL），FDA虽然拒绝批准elamipretide，但指出了一条加速批准路径：接受膝关节伸肌力量作为潜在中间临床终点。这对于Stealth BioTherapeutics就有点难以接受了，这家公司从2019年就试图申报elamipretide上市，因为临床数据争议问题一直和FDA扯到了现在，结果好不容易盼到PDUFA又遭到了延期，延期完了还不算又被拒绝。漫长监管路对于Stealth来说，故事始于2019年，那时Stealth首次向FDA提交elamipretide的审批申请，瞄准的是被称为Barth综合征，这是一种全球仅数百例的超罕见X连锁遗传病，患者多在5岁前早逝，且尚无获批疗法。而这款线粒体靶向肽药物就能通过稳定心磷脂改善线粒体功能，曾获FDA孤儿药、快速通道等资格认定。然而，2021年FDA曾因“缺乏充分且对照良好的试验”拒绝受理其NDA。原因在于提交上市申请的SPIBA-001临床，采用的是将12名患者的II期临床数据和匹配的自然病史进行对照，并没有采用安慰剂对照。在这种背景下，FDA明确要求Stealth在申请批准前，需开展另一项3期临床试验以验证药物疗效。然而，Stealth方面也表达了自身的难处，毕竟这种疾病患者极少，全球III期临床难以展开。选择基于现有2/3期试验数据直接重新提交申请。由于数据不足以支持批准，FDA发出了拒绝受理通知。由于连番遭拒该公司股价不断下跌，最终在2022年被Morningside Venture彻底私有化。不过私有化之后，公司仍未放弃。一波三折的希望转折点出现在2024年3月，经过多次沟通和数据补充，FDA终于接受了Stealth重新提交的elamipretide批准申请，并开始了标准审评流程。5月elamipretide获得了优先审评资格，PDUFA日期被设定在了2025年1月。这一决定背后，是含有安慰剂对照的TAZPOWER试验数据的支撑——该2/3期试验在开放标签阶段不仅验证了6分钟步行距离的改善，还显示Barth综合征症状评估量表得分降低2.1分，膝关节伸肌力量等指标显著提升。在这一背景下，2024年10月FDA专家顾问委员会以10比6的投票结果支持批准elamipretide，公司也在12月提交了数据的相关文件，然而到了今年1月，FDA又提出需要更多时间来审查新提交的数据，让本来应该到达的PDUFA日期拖延到了4月。这还不算完，到了4月初的时候，FDA又通知Stealth由于数据审查的复杂性，可能无法在原定的4月做出决定。而现在，FDA做出了让公司十分迷惑的决定，本来Stealth之前提交的数据就涵盖了膝关节伸肌力量，也要求将其作为终点使用。但现在FDA重复了一遍要求让Stealth用之前已经提交的膝关节伸肌力量数据来作为潜在临床终点作为加速批准途径获批……理论上来说，FDA要求Stealth用已经提交的膝关节伸肌力量数据就能获得加速批准的话，那么Stealth收到的就不该是CRL，而是批准该药物上市的通知。这实在让人摸不着头脑。难道这也是受到特朗普政府裁员的严重影响导致的吗？参考来源：https://www.fiercebiotech.com/biotech/hanging-our-fingernails-stealth-ceo-questions-efficiency-behind-fda-rejection-rare-disease

The snub by the FDA caps off a tumultuous application process for Stealth Bio’s mitochondria-targeting peptide elamipretide. Jeppe Gustafsson via Shutterstock. The US Food and Drug Administration (FDA) has rejected Stealth BioTherapeutics’ elamipretide for the treatment of Barth syndrome after a lengthy review. The complete response letter (CRL) issued by the FDA comes after a 16.5-month priority review cycle and despite a positive vote by an advisory committee (AdComm) meeting. It is not the end of the road for Stealth Bio’s elamipretide, however, with the biotech and the FDA identifying a potential accelerated approval path forward based on a new clinical endpoint. To support a potential new drug application (NDA), Stealth Bio has cut 30% of its workforce to conserve resources. The company used to be publicly traded but went private in 2022. Its last publicly disclosed headcount stood at 38 in 2021. The snub by the FDA caps off a tumultuous application process for Stealth Bio’s mitochondria-targeting peptide elamipretide. The Massachusetts-based biopharma first presented data to the FDA in 2019 as it eyed approval as a treatment for Barth syndrome, an ultra-rare genetic condition caused by a mutation on the X chromosome. Later in 2021, the FDA advised that the company run another Phase III trial. Stealth Bio went ahead with the NDA filing anyway after a feasible trial design was not identified, though the FDA did not even accept the application. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence A new NDA was submitted in January 2024, which the FDA did accept, and that was later converted into a priority review. An AdComm voted 10-6 in favour of Stealth Bio’s drug being an effective treatment of Barth syndrome, but the FDA delayed the Prescription Drug User Fee Act (PDUFA) action date by three months from January to April 2025. This came amid an inspection by the FDA of a third-party manufacturing facility for elamipretide, though Stealth Bio asserts that no specific deficiencies were recorded. The agency then missed the revised deadline, delaying the application again. The CRL eventually followed on 29 May. The path forward is positive for Stealth Bio, but still complex. The FDA has agreed to consider knee extensor muscle strength as a potential intermediate clinical endpoint to support accelerated approval. Stealth Bio had already included data on this in its NDA, showing an improvement of over 45% that lead to improvements in a six-minute walk test (6MWT).  Stealth Bio and the FDA will meet in June 2025 to discuss the proposed post-marketing study. “We recognise that the FDA’s recommendation for an accelerated approval for elamipretide in Barth syndrome offers a path forward for this incurable paediatric disease that affects an incredibly small number of individuals worldwide,” said Reenie McCarthy, Stealth Bio’s CEO. “We hope the FDA will also prioritise ensuring rapid access for neonates affected by the disease subject to appropriate post-marketing safety monitoring,” McCarthy added. Barth syndrome, which primarily affects boys due to its X chromosome mutation pathogenesis, causes heart problems, muscle weakness, and immune system issues. There are currently no FDA-approved therapy for the condition. Pharmaceutical Technology Excellence Awards - Have you nominated? Nominations are now open for the prestigious Pharmaceutical Technology Excellence Awards - one of the industry's most recognised programmes celebrating innovation, leadership, and impact . This is your chance to showcase your achievements, highlight industry advancements , and gain global recognition . Don't miss the opportunity to be honoured among the best - submit your nomination today! Nominate Now