FDA: Despite “Manipulated” Data, $2M Gene Therapy Should Stay on Market

FDA :尽管有“操纵”数据,200万美元的基因治疗应该留在市场上

2019-08-07 23:30:27 Xconomy

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August 6th, 2019 Xconomy National —  [Updated, 7:12 pm ET, see below] The FDA on Tuesday said that some data supporting the spinal muscular atrophy gene therapy Zolgensma was “manipulated” before its May 24 approval and that its manufacturer, Novartis (NYSE: NVS) subsidiary AveXis, knew about it. The FDA stopped short of saying Zolgensma should be pulled from the market, but is nonetheless investigating the matter and threatened potential legal action. An FDA memo issued alongside the Tuesday statement reveals that a member of AveXis, the Zolgensma developer that Novartis acquired in 2018, called the agency in June to say that the company “had manipulated data.” That issue “impacts the accuracy of certain data” from a test in mice that the agency scrutinized during its review process. That, in turn, could alter how the Phase 1 clinical trial results and other animal tests supporting Zolgensma are interpreted. Still, the FDA said that its concerns surround a “small portion of product testing data” that support the method Novartis uses to manufacture Zolgensma. There is no evidence that AveXis manipulated clinical data from patients, for instance, so the agency’s opinion of the safety or effectiveness of Zolgensma hasn’t changed. The FDA “remains confident that Zolgensma should remain on the market.” But it cautioned that an investigation is underway and the agency may “amend [its review] as appropriate.” What’s more, the FDA said that AveXis was aware of the problem before Zolgensma was approved. It didn’t tell the FDA until afterwards. The FDA will “use its full authorities to take action, if appropriate, which may include civil or criminal penalties,” it said in the statement. [Updated with comments from Novartis] Novartis, in a statement issued Tuesday evening, said AveXis “voluntary self-disclosed” the issue to the FDA after it “had become aware of allegations of data manipulation.” Novartis investigated the issue internally as well and shared its findings with the FDA. Novartis noted that the data in question were related to an “older process no longer in use.” The Swiss company added that it is “fully confident in the safety, quality and efficacy” of Zolgensma and will work with the FDA to address any “quality gaps” through the agency’s investigation. Novartis doesn’t expect the situation to delay any of its ongoing Zolgensma regulatory filings or development programs. The nonprofit SMA patient advocacy group Cure SMA said it is “investigating the issue and will report when we have further details.” Zolgensma is one of just two gene therapies approved in the U.S. Gene therapies offer the promise of long-lasting effects, if not outright cures, through a single treatment. But it’s unclear how long they’ll last, and companies and the healthcare system writ large are grappling with how to pay for them. The FDA, for instance, cleared Zolgensma for babies under two years old with SMA, a potentially deadly rare genetic disease. That complicated matters for patients and payers because SMA has a wide range of subtypes, but Novartis so far has provided only early indications that Zolgensma might help patients beyond those with Type 1, the most severe form of the disease. What’s more, an established therapy, nusinersen (Spinraza), from Biogen (NASDAQ: BIIB), is available. The launch of Zolgensma marks the first time a gene therapy has gone head-to-head with an established product. Novartis priced Zolgensma at $2.125 million, to be paid over several yearly installments. Reports have surfaced that some payers have made it difficult for patients to get access to Zolgensma, though Novartis has downplayed those concerns. Will news of manipulated data complicate matters, making it even harder for some patients to get access? Raymond James analyst Steven Seedhouse hinted at such a prospect in a research note, especially “given these optics, which could become more than optics if the data manipulation problem runs deeper.” Biogen shares ticked up about 2 percent in trading on Tuesday. Here’s more on Zolgensma, Spinraza, and SMA. Ben Fidler is Xconomy's Deputy Editor, Biotechnology. You can e-mail him at bfidler@xconomy.com Follow @benthefidler
2019年8月6日 锥形经济 国家—— [更新,下午7:12,见下文] FDA 周二表示,在5月24日批准之前,支持脊髓肌萎缩症基因疗法 Zolgensma 的一些数据被“操纵”,其制造商诺华(Novartis)( NYSE : NVS )子公司 AveXis 也知道这一点。 FDA 没有说 Zolgensma 应该退出市场,但仍在调查此事,并威胁潜在的法律行动。 FDA 在周二声明的同时发布的一份备忘录显示,诺华(Novartis)于2018年收购的 Zolgensma 开发商 AveXis 的一名成员在6月份称该公司“操纵了数据”。这一问题“影响某些数据的准确性”,来自该机构在审查过程中审查的老鼠试验。这进而可能改变第一阶段临床试验结果和支持佐尔甘马的其他动物试验的解释。 不过, FDA 表示,它的担忧围绕着“一小部分产品测试数据”展开,这些数据支持诺华(Novartis)生产 Zolgensma 的方法。例如,没有证据表明 AveXis 操纵了患者的临床数据,因此该机构对 Zolgensma 的安全性或有效性的看法没有改变。FDA “仍然相信佐尔甘斯曼应该继续留在市场上。”但该机构警告称,一项调查正在进行中,并可能“酌情修改(其审查结果)。” 更重要的是, FDA 说 AveXis 在 Zolgensma 被批准之前就意识到了这个问题。直到后来才告诉 FDA 。FDA 在声明中表示,将“酌情利用其全部权力采取行动,可能包括民事或刑事处罚。” 诺华(Novartis)在周二晚间发布的一份声明中表示, AveXis “自愿自我披露”了该问题,此前该公司“已意识到数据操纵的指控”。诺华(Novartis)公司在内部进行了调查,并与 FDA 分享了调查结果。诺华(Novartis)指出,这些数据与“不再使用的旧程序”有关。 瑞士公司补充称,对佐尔甘马的安全性、质量和有效性“完全有信心”,并将与 FDA 合作,通过该机构的调查解决任何“质量差距”。诺华(Novartis)预计这种情况不会延迟其正在进行的 Zolgensma 监管申报或开发项目。 非营利性的 SMA 患者倡导组织 Cure SMA 表示,它正在“调查这个问题,并将在我们有更多细节时报告。” Zolgensma 是美国仅有的两种基因疗法之一,基因疗法通过单一的治疗提供了持久的效果,即使不是彻底治愈。但目前还不清楚它们会持续多久,企业和医疗保健系统巨头都在努力解决如何为它们买单的问题。 例如, FDA 为两岁以下的婴儿清除了一种可能致命的罕见遗传病 SMA 。这对患者和付款人来说很复杂,因为 SMA 有广泛的亚型,但诺华(Novartis)迄今只提供了早期的迹象,表明佐尔根瘤可能帮助患者超过1型,最严重的疾病。更重要的是,一种成熟的治疗方法,来自百健(Biogen)( NASDAQ : BIIB )的 Nusinersen ( Spiraza )是可用的。Zolgensma 的推出标志着基因治疗首次在已有产品的基础上走向成熟。 诺华(Novartis)公司给佐尔甘斯曼定价为212.5万美元,分几年分期支付。有报道称,一些付费患者很难获得 Zolgensma ,尽管诺华(Novartis)公司已经淡化了这些担忧。被操纵数据的消息是否会使事情变得复杂,使一些患者更难获得信息?Raymond James 分析师 StevenSeedhouse 在一份研究报告中暗示了这样的前景,尤其是“考虑到这些光学,如果数据操作问题变得更深,光学可能会变得比光学更重要。” 百健(Biogen)股价周二上涨约2%。 更多关于 Zolgensma 、 Spiraza 和 SMA 。 Ben Fidler 是 Xconomi 的生物技术副编辑。您可以通过电子邮件发送到 bfidler @ xconomi.com Follow @ benthefidler

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