Sarepta Stock Falls as FDA Denies Approval to Golodirsen

FDA拒绝批准Sarepta Therapeutics杜氏肌营养不良疗法,有感染风险和肾脏毒性

2019-08-21 15:02:00 Zacks

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Sarepta Therapeutics, Inc. SRPT announced that the FDA has rejected the application for the approval of its exon 53 skipping candidate, golodirsen. The company had filed a new drug application in December last year seeking accelerated approval for the candidate as a potential treatment for Duchenne muscular dystrophy . The FDA issued a complete response letter (“CRL”) against the NDA for golodirsen, citing two concerns – the risk of infections related to intravenous infusion ports and renal toxicity seen in pre-clinical models. Sarepta stated that renal toxicity in pre-clinical models was observed in doses ten times the dose used in clinical studies. The renal toxicity issue raised in the CRL were not observed in the clinical study – Study 4053-101 – which formed the basis for golodirsen NDA. Shares of the company fell more than 13% in after-hours market on Aug 19, following the announcement. However, the stock has gained 10.3% so far this year against the industry’s decrease of 2% as demand for its sole marketed DMD drug, Exondys 51, remains strong. The CRL comes as a surprise for investors and the company as no issues related to golodirsen NDA were raised by the FDA during the entire review period that could have led to non-approval of the candidate. In February, the FDA had granted priority review to the NDA. Moreover, on its second-quarter earnings release, the company announced that the FDA has conditionally approved the trade name of Vyondys 53 for golodirsen. Sarepta was ready to launch the drug immediately following the potential approval. The company has one marketed drug – Exondys51 – for treating exon 51 skipping DMD. The drug has the potential to address up to 13% of the total DMD population. The FDA’s decision to reject golodirsen NDA is likely to hit the company’s near-term growth as the approval would have increased the eligible DMD patient population by 8%. Sarepta will work with the FDA to address the issues raised in the CRL and find a path to get the candidate approved as early as possible. The company is planning to request a meeting with the FDA soon. Meanwhile, the company is evaluating the safety profile of golodirsen in an ongoing phase III study – ESSENCE – along with another DMD candidate, casimersen. The company is also evaluating golodirsen and casimersen in a phase III open-label extension study, which is currently enrolling patients. Casimersen is an exon 45 skipping DMD candidate and the company is likely to file an NDA seeking approval for the candidate by the year end. Apart from golodirsen and casimersen, Sarepta is also developing next-generation PPMO platform candidate, SRP-5051, in DMD patients amenable to exon 51 skipping and gene therapies targeting DMD and other muscular dystrophies as well as central nervous system disorders. Meanwhile, there are several other companies developing gene therapies for treating DMD including Solid Biosciences SLDB, Audentes Therapeutics BOLD and Pfizer PFE.
Sarepta Therapeutics , Inc . SRPT 宣布, FDA 已拒绝批准其外显子53跳过候选人 goldodirsen 的申请。去年12月,该公司提交了一份新药申请,寻求加速批准该候选人,作为杜氏肌营养不良的潜在治疗方法。 FDA 针对戈罗定的 NDA 发布了一份完整的应答信(“ CRL ”),提到了两个问题——与静脉输液口相关的感染风险和临床前模型中的肾脏毒性。 Sarepta 说,临床前模型中的肾毒性是临床研究中使用剂量的10倍。CRL 中提出的肾脏毒性问题并未在临床研究中得到观察——研究4053-101——这是戈罗定 NDA 的基础。 消息公布后,该公司股价在8月19日盘后交易市场下跌逾13%。然而,由于其唯一上市的 DMD 药物 Exondys 51的需求依然强劲,该股今年迄今已上涨10.3%,而该行业的跌幅为2%。 CRL 令投资者和公司感到意外,因为 FDA 在整个审查期内没有提出与 goldodirsen NDA 相关的问题,这可能导致该候选人未获批准。2月, FDA 授予 NDA 优先审查。此外,在第二季度收益公布时,该公司宣布, FDA 有条件批准了戈罗定公司 Vyondi 53的商品名。Sarepta 在获得潜在批准后立即准备上市。 该公司有一种上市药物—— Exondys51——用于治疗外显子51跳过 DMD 。该药物有潜力处理高达13%的总 DMD 人口。FDA 拒绝戈罗定 NDA 的决定很可能会影响到该公司的近期增长,因为批准将使符合条件的 DMD 患者增加8%。 Sarepta 将与 FDA 合作解决在 CRL 中提出的问题,并找到一条途径,使候选人尽快获得批准。该公司计划很快向 FDA 要求召开会议。与此同时,该公司正在进行的第三阶段研究—— ESSECE ——与另一位 DMD 候选人 Casimersen 一道,评估 goldodisen 的安全状况。该公司还在评估 goldodirsen 和 casimersen 的 III 期开放标签扩展研究,目前正在招募患者。 Casimersen 是一个外显子45跳过 DMD 的候选人,该公司很可能会在年底之前提交 NDA ,寻求该候选人的批准。 除了 goldodirsen 和 casimersen 之外, Sarepta 还在 DMD 患者中开发下一代 PPMO 平台候选物 SRP-5051,该候选药物可用于外显子51跳过和针对 DMD 和其他肌肉营养不良以及中枢神经系统疾病的基因治疗。 同时,还有其他几家公司正在开发用于治疗 DMD 的基因疗法,包括固体生物科学 SLDB 、 Authenties Therapeutics BOLD 和辉瑞(Pfizer) PFE 。

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