里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!

2021年6月26日,Intellia 和 Regeneron宣布具有里程碑意义的CRISPR疗法临床数据,显示单次输注 NTLA-2001后致病蛋白的显著减少,NTLA-2001是一种针对转甲状腺素蛋白 (ATTR) 淀粉样变性的在研CRISPR疗法。


这是首个支持人体体内CRISPR基因组编辑安全性和有效性的临床数据。

正在进行的1 期试验的中期数据显示,单剂量0.3 mg/kg的NTLA-2001导致血清TTR平均降低87%,到第28天血清TTR降低最多,达96%,具有剂量依赖性反应。

安全数据令人鼓舞。到第28天,前6名患者未观察到严重不良事件。

数据发表在《新英格兰医学杂志》上,并在外周神经学会年会 (PNS) 上展示。

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!

John Leonard医学博士(来源:公司官网)


Intellia 总裁兼首席执行官John Leonard医学博士表示:

“这是有史以来第一个临床数据,表明我们通过单次静脉输注CRISPR来精确地编辑体内的靶细胞,从而治疗遗传疾病。中期结果支持我们的信念,即NTLA-2001有可能通过单次剂量阻止和逆转ATTR淀粉样变性的破坏性并发症。正如我们在NTLA-2001中所做的那样,解决将CRISPR/Cas9靶向递送到肝脏的挑战也为我们的模块化平台打开了治疗各种其他遗传疾病的大门,我们打算迅速采取行动推进和扩大我们的管线。


我们相信,有了这些数据,我们真正开启了医学的新时代。”

药时代热烈祝贺!

了解详情,请阅读公司新闻稿。

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!


Intellia and Regeneron Announce Landmark Clinical Data Showing Deep Reduction in Disease-Causing Protein After Single Infusion of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis


Jun 26, 2021

  • First-ever clinical data supporting safety and efficacy of in vivo CRISPR genome editing in humans

  • Interim readout in ongoing Phase 1 trial finds single 0.3 mg/kg dose of NTLA-2001 led to 87% mean reduction in serum TTR, with a maximum 96% serum TTR reduction by day 28, with dose-dependent response

  • Encouraging safety profile; no serious adverse events observed in the first six patients by day 28

  • Data published in The New England Journal of Medicine and presented at Peripheral Nerve Society Annual Meeting (PNS)

  • Intellia to host investor event on Monday, June 28 at 8:00 a.m. E.T.


CAMBRIDGE, Mass. and TARRYTOWN, N.Y.June 26, 2021 (GLOBE NEWSWIRE) — Intellia Therapeutics, Inc. (NASDAQ:NTLA) and Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN) today announced positive interim data from an ongoing Phase 1 clinical study of their lead in vivo genome editing candidate, NTLA-2001, which is being developed as a single-dose treatment for transthyretin (ATTR) amyloidosis. The Phase 1 study, run by Intellia as the program’s development and commercialization lead, is evaluating NTLA-2001 in people living with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). NTLA-2001 is the first CRISPR/Cas9-based therapy candidate to be administered systemically, via intravenous infusion, for precision editing of a gene in a target tissue in humans. NTLA-2001 is designed to inactivate the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR) protein, which accumulates in tissues throughout the body and causes the debilitating and often fatal complications of ATTR amyloidosis. The interim data were presented today at the 2021 Peripheral Nerve Society (PNS) Annual Meeting and published in The New England Journal of Medicine (nejm.org/doi/full/10.1056/NEJMoa2107454.)1.

“These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR. The interim results support our belief that NTLA-2001 has the potential to halt and reverse the devastating complications of ATTR amyloidosis with a single dose,” said Intellia President and Chief Executive Officer John Leonard, M.D. “Solving the challenge of targeted delivery of CRISPR/Cas9 to the liver, as we have with NTLA-2001, also unlocks the door to treating a wide array of other genetic diseases with our modular platform, and we intend to move quickly to advance and expand our pipeline. With these data, we believe we are truly opening a new era of medicine.”

The interim data released today cover the first six ATTRv-PN patients across two single-ascending dose cohorts of the Phase 1 study, which is currently being conducted in the United Kingdom and New Zealand. Single doses of either 0.1 mg/kg or 0.3 mg/kg of NTLA-2001 were administered systemically. Reductions in serum TTR levels were measured from baseline to day 28. Treatment with NTLA-2001 led to dose-dependent reductions in serum TTR, with mean reductions of 52% among the three patients in the 0.1 mg/kg dose group, and 87% among the three patients in the 0.3 mg/kg dose group, including one patient with a 96% reduction. By contrast, the standard of care for ATTRv-PN, which requires chronic treatment, typically yields TTR reductions of approximately 80%.

“This is exciting early data both for people living with this devastating disease and for the entire scientific community working to maximize the potential of genetics-based medicines through cutting-edge research and technologies,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron, which first partnered with Intellia in 2016 to advance CRISPR/Cas9 gene-editing technology for in vivo therapeutic development. “Thanks to large-scale human genetics research, there have been many new genetic targets identified and confirmed to have an impact on human health. Combining this knowledge with the precision and enhanced convenience of a single CRISPR infusion unlocks new possibilities in treating – and potentially even curing – life-threatening and historically difficult-to-address diseases.”

At both dose levels, NTLA-2001 was generally well-tolerated by the six patients included in the interim analysis, with no serious adverse events and no liver findings by day 28. Given the safety and tolerability profile so far, NTLA-2001 is continuing to be evaluated in the dose-escalation portion of the study, to determine if a higher dose could result in a deeper reduction in disease-causing protein levels leading to the potential for more meaningful clinical benefit. As of the date of this release, Cohort 3, evaluating NTLA-2001 at the 1 mg/kg dose level, is actively enrolling.

Following the identification of a recommended dose in the dose-escalation portion of the study, Intellia expects to begin a single-dose expansion cohort in Part 2 of the Phase 1 trial later this year. After completion of the Phase 1 trial, the company plans to move to pivotal studies for both polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis.

“ATTR amyloidosis is a progressive and fatal disease that usually requires chronic, lifelong treatment. These interim Phase 1 data support NTLA-2001 as the only one-time treatment either on the market or in development,” said Julian Gillmore, M.D., Ph.D., Professor of Medicine, National Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, U.K., and the Phase 1 study’s national coordinating investigator. “As the first-ever systemically administered CRISPR therapy candidate, NTLA-2001 shows strong potential to stop the production and accumulation of the misfolded TTR protein by inactivating the TTR gene at the root of the disease. This approach could deliver life-changing, lifelong benefits to patients with all forms of ATTR amyloidosis, who continue to experience debilitating symptoms and complications of disease while on the standard of care. While further investigation is needed, these results are highly encouraging.”

Intellia intends to present additional data from the study at a medical or scientific meeting later this year.

Gillmore JD, Gane E, Taubel J, et al. CRISPR /Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 2021. nejm.org/doi/full/10.1056/NEJMoa2107454

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!
END
版权声明/免责声明
本文为转载,仅供感兴趣的个人谨慎参考,非商用,非医用、非投资用。
欢迎朋友们批评指正!衷心感谢!
文中图片为授权正版图片,或来自微信公共图片库,或取自网络
根据CC0协议使用,版权归拥有者。
任何问题,请与我们联系。衷心感谢!
投稿点这里!
加入我们点这里!

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!

推荐阅读

里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!
里程碑!全球人体CRISPR基因编辑临床试验结果首次公布!数据积极,标志着基因编辑时代到来!点击这里,欣赏更多精彩内容!

本篇文章来源于微信公众号:药时代

发布者:药时代,转载请首先联系contact@drugtimes.cn获得授权

分享本页
返回顶部