Intellia Therapeutics has patients lined up in the U.S. for a phase 2 trial of a CRISPR-based treatment in hereditary angioedema, but the FDA has thrown down a roadblock over a request for a new preclinical test of the therapy’s impact on a developing fetus.

Intellia Therapeutics让患者在美国排队进行基于CRISPR的遗传性血管性水肿治疗的2期临床试验，但FDA要求对该疗法对发育中的胎儿的影响进行新的临床前测试，从而犯下了障碍。

The FDA has asked the gene editing biotech for additional preclinical data on the inclusion of female patients of child-bearing potential. An investigative new drug application was approved for NTLA-2002 by the agency in March, but the request for an additional animal test means Intellia is revising plans for the 55-person trial..

FDA已要求gene editing biotech提供有关纳入具有生育潜力的女性患者的额外临床前数据。该机构于3月批准了一项针对NTLA-2002的新药调查申请，但要求进行额外的动物试验意味着Intellia正在修订55人试验的计划。。

The good news, according to CEO John Leonard, is that sites outside the U.S. were happy to fill the enrollment gap. On a second-quarter earnings call this morning, the executive said the trial is proceeding “extremely quickly” without U.S. patients, so it will go on mostly as planned.

根据首席执行官John Leonard的说法，好消息是美国以外的网站很乐意填补招生空白。在今天早上的第二季度收入电话中，行政人员表示，在没有美国患者的情况下，试验正在“极快”进行，因此它将按计划进行。

Intellia will conduct the requested preclinical study and hopes to get the FDA’s blessing to use U.S. patients in a phase 3 trial, which Leonard said could begin as early as the third quarter of 2024.

Intellia将进行所要求的临床前研究，并希望获得FDA的祝福，以便在第3阶段试验中使用美国患者，伦纳德表示最早可在2024年第三季度开始。

Intellia could have proceeded with the U.S. portion of the study by filing a protocol amendment to exclude women of child-bearing potential but decided not to, a company spokesperson told Fierce Biotech. “While we do have the option to enroll U.S. patients with the exclusion of women of child-bearing potential through a protocol amendment, the global interest in NTLA-2002 enables us to proceed more quickly to a Phase 3 study by fully enrolling Phase 2 in other countries,” the company said in a statement..

Intellia可以通过提交协议修正案来排除美国部分的研究，以排除有生育潜力的女性，但决定不这样做，一位公司发言人告诉Violet Biotech。“虽然我们确实可以通过议定书修正案在排除有生育潜力的妇女的情况下招收美国患者，但NTLA-2002的全球兴趣使我们能够通过在其他国家全面招收第二阶段来更快地进行第三阶段研究，”该公司在一份声明中说。。

While leaders tried to couch the FDA setback with the news that enrollment had gone ahead anyway, analysts peppered Leonard and his fellow executives with questions on the earnings call.

尽管领导者们试图将FDA的挫折与招生工作继续进行的消息联系起来，但分析师却对伦纳德及其同事高管提出了关于盈余电话的问题。

The situation immediately brought to mind the clinical hold placed in November 2022 on Verve Therapeutics over concerns that gene edits from its high cholesterol gene editing therapy could pass on to children. This is known as germline editing and has been a key concern as gene editing overtakes the clinic.

这种情况立即让人想起2022年11月对Verve Therapeutics的临床持有，担心其高胆固醇基因编辑疗法的基因编辑可能会传递给儿童。这被称为种系编辑，随着基因编辑超越临床，这一直是一个关键问题。

As of a May earnings update, Verve was still working toward resolving the hold for VERVE-101..

截至5月收益更新，Verve仍在努力解决Verve-101的持有问题。。

Leonard did not say the words “clinical hold” and was careful to note that Intellia already submitted preclinical breeding studies for the IND request that he believes allay concerns about germline editing with the company’s products.

伦纳德没有说“临床持有”这个词，而是小心地注意到Intellia已经为IND要求提交了临床前育种研究，他相信对公司产品的种系编辑的担忧。

“That is not what this is. That question has been addressed with information that was supplied with the already-cleared IND,” Leonard said. “So as far as we can tell in our dealings with the FDA and every other regulatory agency, that particular germline question has been put to rest with the data that we’ve supplied.”.

伦纳德说：“这不是事实，这个问题已经通过已经清除的IND提供的信息得到解决。“据我们所知，在我们与FDA和其他监管机构的交易中，特定的种系问题已经与我们提供的数据保持一致。”。

Instead, the FDA wants to know whether the embryological development of the fetus in mice is affected in any way by chemicals that are in the lipid nanoparticle systems used to deliver NTLA-2002. The only thing different with the FDA’s request, according to Leonard, is that this specific test is being requested earlier in the development timeline than expected..

相反，FDA想知道小鼠胎儿的胚胎发育是否受到用于递送NTLA-2002的脂质纳米颗粒系统中的化学物质的任何影响。伦纳德认为，与FDA的要求唯一不同的是，这个具体的测试在开发时间表上比预期的要早。。

“We’ve looked at germline cells specifically, we know that they’re unaffected,” Leonard said. He also noted that there was no specific safety data that spurred the FDA’s request. “Our view is that this is the FDA taking a very considered view of the space and looking for us to fill out what is a typical set of data that usually is supplied a little later in a program.”.

伦纳德说：“我们专门研究了种系细胞，我们知道它们不受影响。他还指出，没有具体的安全数据刺激FDA的要求。“我们的观点是，这是FDA对空间进行了非常仔细的考虑，并希望我们填写通常在计划稍后提供的典型数据集。”。

The FDA and Intellia have already come to an agreement on what’s needed, which will be an “abbreviated study” that the company is already “well on our way to completing,” according to Leonard.

伦纳德说，FDA和Intellia已经就所需内容达成了协议，这将是一项“缩写研究”，该公司已经“在我们完成之路上”了。

Meanwhile, enrollment has filled up at the ex-U.S. sites, and that includes women of child-bearing potential. Leonard said there was plenty of enthusiasm from U.S. clinicians and patients to participate, but working through these issues for the phase 2 would have “delayed the study substantially.” The goal of the trial is to establish the phase 3 dose..

与此同时，在前美国的网站上填写了入学申请，其中包括有生育潜力的妇女。伦纳德说，美国临床医生和患者参与的积极性很高，但是在第二阶段解决这些问题将会“大大推迟研究”。试验的目标是确定第三阶段的剂量。。

“We will have an abundance of U.S. patients that I think will be well prepared to begin the phase 3 program potentially as early as the third quarter of next year and that’s what we’re working towards,” Leonard said.

伦纳德说：“我们将有大量的美国患者，我认为他们很可能早在明年第三季度就开始实施第三阶段计划，这就是我们正在努力的目标。”。

Coincidentally, Chief Medical Officer David Lebwohl, M.D., noted that many patients with hereditary angioedema are scrambling to get into the trial in the hope that their conditions can be improved so they can go on to have successful pregnancies.

巧合的是，首席医疗官David Lebwohl博士指出，许多遗传性血管性水肿患者正在努力进入试验阶段，希望他们的病情得到改善，以便他们能够继续成功怀孕。

“Of course, we look forward to bringing that great result forward in the future if we can,” Lebwohl said. He does not expect any differences between males and females, older or younger women when data collection begins. Intellia will be monitoring any future pregnancies as part of long-term follow-up..

Lebwohl说：“当然，如果能够的话，我们期待在未来带来这一伟大成果。当数据收集开始时，他不期望男性和女性，年长或年轻女性之间有任何差异。作为长期随访的一部分，Intellia将监测未来的任何怀孕。。

Analysts wondered whether there was any read-through to the rest of Intellia’s pipeline. Leonard assured them that there should not be any impact on the company’s other programs, including star ATTR amyloidosis therapy NTLA-2001. That disease typically impacts older patients, particularly men, anyway, according to Leonard..

分析师想知道Intellia的其余管道是否有通读。伦纳德向他们保证，不应对公司的其他计划产生任何影响，包括star ATTR淀粉样变性治疗NTLA-2001。伦纳德说，这种疾病通常会影响老年患者，尤其是男性。。

Intellia’s shares were mostly steady in the opening hours of trading at $38.98, down just under 2% from $40.96 at yesterday’s close.

Intellia的股票在交易开放时间基本稳定，为38.98美元，比昨天结束时的40.96美元下降了不到2%。