Pictured: Three doctors holding their thumbs up/iStock, andrei_r

图：三位医生举起大拇指/iStock，andrei r

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee on Tuesday agreed that Vertex Pharmaceuticals had sufficiently demonstrated the safety of its investigational sickle cell disease gene-edited therapy exagamglogene autotemcel (exa-cel).

美国食品及药物管理局细胞，组织和基因治疗咨询委员会星期二同意Vertex Pharmaceuticals已经充分证明了其研究镰状细胞病基因编辑疗法exagamglogene autotemcel（exa-cel）的安全性。

Still, the panel of external experts did indicate that Vertex and its partner CRISPR Therapeutics could follow treated patients and assess them specifically for potential off-target effects. The companies can implement this in their post-approval, long-term follow-up program, the adcomm concluded.

尽管如此，外部专家小组确实表明，Vertex及其合作伙伴CRISPR Therapeutics可以跟踪接受治疗的患者，并专门评估其潜在的脱靶效应。adcomm总结说，这些公司可以在批准后的长期后续计划中实施这一点。

In their regulatory application, Vertex and CRISPR provided data from a pivotal Phase I/II/III trial and bolstered these up with long-term safety and efficacy results from a follow-up study. The partners have also proposed a 15-year post-approval follow-up study using a registry to monitor patients treated with exa-cel..

在他们的监管应用中，Vertex和CRISPR提供了关键I/II/III期试验的数据，并通过后续研究的长期安全性和有效性结果支持这些数据。合作伙伴还提出了一项为期15年的批准后随访研究，使用登记处监测接受exa-cel治疗的患者。。

“We want to be careful to not let the perfect be the enemy of the good,” Scot Wolfe, professor at the Department of Molecular, Cell and Cancer Biology at UMass Chan Medical School and an adcomm member, said during Tuesday’s meeting.

乌马斯陈医学院分子，细胞和癌症生物学系教授兼adcomm成员斯科特·沃尔夫（Scot Wolfe）在星期二会议上说：“我们要小心，不要让完美成为敌人。”。

“Right now, I feel that you can do a lot of in-depth analysis … and you want to do as good a job as you possibly can, but at some point, you have to just try things out in patients and I think in this case, there’s a huge unmet need for individuals with sickle cell disease.”

“现在，我觉得你可以做很多深入的分析……你想尽可能做得好，但在某些时候，你只需要在病人身上尝试一些事情，我想在这种情况下，镰状细胞病患者的需求尚未得到满足。”

Unlike the typical adcomm meeting, Tuesday’s session did not focus on the efficacy of exa-cel nor did the panel weigh its benefits against its risks. Instead, the advisers had been instructed to specifically discuss whether Vertex and CRISPR had conducted a sufficiently thorough analysis of the potential off-target effects of exa-cel..

与典型的adcomm会议不同，星期二的会议没有关注exa-cel的功效，专家组也没有权衡其风险的好处。相反，顾问们被指示专门讨论Vertex和CRISPR是否对exa-cel的潜在脱靶效应进行了充分彻底的分析。。

In a briefing document published ahead of the Tuesday meeting, FDA staff said that Vertex and CRISPR’s in silico methods to spot these possible unintended edits leveraged “insufficient sequencing data” as a reference, which in turn might “impede the identification of relevant variants contributing to off-target editing.”.

FDA工作人员在本星期二会议前发表的一份简报文件中表示，Vertex和CRISPR的计算机模拟方法指出了这些可能的意外编辑，这些方法利用“测序数据不足”作为参考，这反过来可能“阻碍识别有助于脱靶编辑“。

Specifically, the regulator raised concerns that the reference databases used to predict these off-target edits may not be representative of the sickle cell disease (SCD) population.

具体而言，监管机构担心用于预测这些脱靶编辑的参考数据库可能无法代表镰状细胞病（SCD）人群。

Vertex and CRISPR are seeking the FDA’s approval for exa-cel, an autologous and ex vivo gene therapy that leverages a patient’s own stem cells—genetically edited using the CRISPR/Cas9 system—to induce high production levels of fetal hemoglobin.

Vertex和CRISPR正在寻求FDA批准exa-cel，这是一种自体和离体基因疗法，利用患者自身的干细胞进行基因编辑，使用CRISPR/Cas9系统诱导高水平的胎儿血红蛋白。

If approved, exa-cel could become the “first genetic therapy available to approximately 20,000 people with severe SCD in the U.S.,” according to CRISPR’s news release on Tuesday announcing the conclusion of the adcomm meeting. The FDA is set to release its decision on exa-cel by Dec. 8.

根据CRISPR在星期二宣布adcomm会议结束的新闻稿，如果获得批准，exa-cel可能成为“美国约20000名严重SCD患者可获得的第一种基因疗法”。FDA将于12月8日发布关于exa-cel的决定。

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Tristan Manalac是位于菲律宾大马尼拉的独立科学作家。他可以联系到tristan@tristanmanalac.com或者tristan.manalac@biospace.com.