Stealth BioTherapeutics, Inc.

A US Food and Drug Administration (FDA) panel of experts has voted in support of Stealth BioTherapeutics’ elamipretide for Barth syndrome, an ultra-rare genetic disease that affects approximately 150 people in the US. There are currently no therapies approved by the regulator for Barth syndrome, which primarily occurs in males and is characterised by cardiac abnormalities. The disease leads to muscle weakness, exercise intolerance, fatigue, heart failure, recurrent infections and delayed growth, and is associated with a reduced life expectancy. The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted ten to six in favour of Stealth’s application for elamipretide, concluding that the drug is effective for this patient population. Among the evidence supporting the committee’s decision was positive results from the TAZPOWER part two baseline-controlled extension study, the late-stage SPIBA-001 natural history control study, as well as supportive biomarker and preclinical data. Stealth’s chief executive officer, Reenie McCarthy, said: “We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package… and recognised that this data supports the potential of elamipretide to improve the lives of patients with this devastating disease.” The CRDAC’s vote will now be considered by the FDA as it completes its independent review of elamipretide in this indication, with a final decision expected in January 2025. Elamipretide has already been granted orphan drug, fast track and rare paediatric disease designations by the FDA, as well as orphan drug designation by the European Medicines Agency for Barth syndrome. The drug is also being evaluated in late-stage trials for primary mitochondrial myopathy and dry age-related macular degeneration. Beyond elamipretide, Stealth is evaluating a topical ophthalmic formulation of its clinical-stage candidate bevemipretide for dry age-related macular degeneration, and has a pipeline of compounds under evaluation for rare neurological and cardiac disease indications. The vote on elamipretide comes just one month after the company was awarded a grant from the Friedreich’s Ataxia (FA) Research Alliance to evaluate its mitochondria-targeted molecule SBT-589 in FA, an inherited disease that causes progressive damage to the nervous system and estimated to affect one in 50,000 individuals in the US.

▎药明康德内容团队编辑 Stealth BioTherapeutics今天宣布，美国FDA心血管和肾脏药物咨询委员会（CRDAC）以10比6的票数支持该公司在研疗法elamipretide用于治疗巴思综合征（Barth syndrome）患者。该疗法的新药申请（NDA）已获得优先审评资格，FDA预计在2025年1月29日以前公布审评结果。如果获得批准，elamipretide将成为巴思综合征的首款获批疗法。 CRDAC讨论了elamipretide用于治疗巴思综合征的益处和风险，包括TAZPOWER试验第2部分基线对照扩展研究的结果、SPIBA-001临床3期试验自然史对照研究的结果，以及其他支持性生物标志物和临床前数据。CRDAC的投票虽然不具约束力，但美国FDA在就elamipretide治疗巴思综合征做出潜在批准决定时会考虑该投票结果。 巴思综合征是一种危及生命、极为罕见的遗传性线粒体疾病，其特征是患者的心脏异常，导致其运动不耐受、肌肉无力、虚弱性疲劳、心力衰竭、反复感染和生长迟缓。患者的的预期寿命通常较短，85%患者的死亡发生在5岁之前。巴思综合征主要发生在男性身上，据估计，全球每1百万名男性中有1人患有该病。目前尚无美国FDA或欧洲药品管理局（EMA）批准针对巴思综合征患者的疗法。 Elamipretide是一种肽化合物，可轻易穿透细胞膜，靶向线粒体内膜，并可逆性地与心磷脂（cardiolipin）结合。在临床前或临床研究中观察到该疗法可增加线粒体呼吸作用、改善电子递送链功能和ATP生成，并减少致病性活性氧（ROS）的形成。这种elamipretide-心磷脂结合已被证明可以使线粒体内膜结构正常化，从而改善线粒体功能。除了正在接受用以治疗巴思综合征的审评外，该疗法还处于治疗原发性线粒体肌病和干性年龄相关性黄斑变性的后期开发阶段。Elamipretide已获得美国FDA授予孤儿药资格、快速通道资格和罕见儿科疾病认定，以及EMA的孤儿药资格，用于治疗巴思综合征。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Stealth BioTherapeutics Announces Positive Vote from FDA Advisory Committee Meeting Supporting Potential Approval of Elamipretide for the Treatment of Barth Syndrome. Retrieved October 11, 2024 from https://stealthbt.com/stealth-biotherapeutics-announces-positive-vote-from-fda-advisory-committee-meeting-supporting-potential-approval-of-elamipretide-for-the-treatment-of-barth-syndrome/ [2] Programs & Pipeline. Retrieved October 11, 2024 from https://stealthbt.com/programs-pipeline/#pipeline 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

This week, Stealth BioTherapeutics CEO Reenie McCarthy faced a seemingly insurmountable roadblock with the company’s drug for the ultra-rare, fatal mitochondrial disease Barth syndrome. FDA reviewers had extensively questioned the data supporting the drug’s efficacy. And the agency had already turned down Stealth once. Instead, the advisory committee on Thursday voted 10-6 in support of the drug, following testimony from patients and their families, as well as doctors who had treated patients with it. The result was a substantial win for the small, 50-person private company and its CEO. McCarthy joined Endpoints News via Zoom on Friday to discuss the surprise vote. “We’ve had a lot of ups and downs along the way, and we really tried to keep progressing the program despite some of the disappointments because of the strong belief that we had a drug that was working for patients living with this terrible disease,” McCarthy said. Barth syndrome affects about 130 American boys, and 80% don’t survive past 5 years of age. However, Stealth’s proposed indication for the drug is for 12 years and older, and the population in which the drug was studied was mostly older teenagers and children. “That’s an FDA decision,” McCarthy said, noting there are about 20 to 25 boys on the drug through an expanded access program. “We certainly profiled some of our expanded access in our presentation, really to speak to the safety that we’ve seen in younger children.” She said the company has had requests for the drug from 10 countries and a dozen US hospitals, noting patients and their families don’t pay for treatment under those expanded access efforts. The FDA has until Jan. 29, 2025, to make a final approval decision. McCarthy declined to discuss potential pricing ahead of an elamipretide approval, and said the company plans to conduct a pharmacokinetic study in younger children to optimize dosing. “You know what the price tags of drugs for super-rare diseases are,” McCarthy said. “We’re going to have to take that into consideration. But super-rare diseases are a little bit less of a problem from a payer perspective as well, because there’s a lot less patients affected by them.” CDER Director Patrizia Cavazzoni, who typically doesn’t speak at advisory committee meetings, made a comment just prior to Thursday’s vote about regulatory flexibility and how the agency is evolving its work in ultra-rare indications. McCarthy said it was the first time anyone in the FDA’s leadership had indicated that there might be some flexibility afforded to elamipretide.