TAK-861

▎药明康德内容团队编辑 CRISPR基因编辑疗法让遗传性血管性水肿患者疾病发作率降低98% Intellia Therapeutics今天宣布了在研疗法NTLA-2002正在进行的1/2期研究中1期部分的长期数据。NTLA-2002是一款CRISPR基因编辑疗法，正在开发为治疗遗传性血管性水肿（HAE）的一次性治疗方案。HAE是一种罕见的遗传病，会导致可能危及生命的肿胀发作。 在所有患者中，中位随访时间为20.1个月时，单次NTLA-2002治疗让患者月均疾病发作率平均减少了98%，中度至重度发作平均减少了99%。在测试的每个剂量水平上，HAE发作率均显著减少。单次输注后，患者最长的无发作期超过26个月，并且仍在持续。此外，HAE症状最严重的患者中，发作减少的效果也非常显著。研究开始时每月HAE发作率最高的两位患者（分别为16.8和14.0次/月）在16周的主要观察期结束时无发作，并且在最新的随访中依然无发作。这两位患者中最长的无发作持续时间为23.5个月，并且仍在持续。此外，100%接受NTLA-2002治疗的患者在停止其他预防性治疗后后无需再进行预防性治疗。 NTLA-2002是一种体内CRISPR基因编辑候选疗法，通过脂质纳米颗粒（LNP）以mRNA形式递送CRISPR-Cas9基因编辑系统，靶向敲除血浆前激肽释放酶基因（KLKB1），以永久性降低血浆中激肽释放酶活性，从而防止遗传性血管水肿的发作。 治疗神经退行性疾病，礼来超6亿美元囊获潜在“best-in-class”ASO疗法 QurAlis公司宣布与礼来公司（Eli Lilly and Company）达成了一项独家许可协议，QurAlis将授予礼来在全球范围内开发和商业化在研疗法QRL-204的权益。QRL-204是一款潜在“best-in-class”的剪接调节反义寡核苷酸（ASO）疗法，旨在恢复肌萎缩性侧索硬化症（ALS）、额颞叶痴呆（FTD）及其他神经退行性疾病中的UNC13A功能。 QurAlis将获得4500万美元的预付款及额外的股权投资。此外，QurAlis还有资格获得高达5.77亿美元的里程碑付款。该协议包括一项研发合作，利用QurAlis的专有FlexASO剪接调节平台，以识别和开发其他靶向UNC13A的候选药物。QurAlis的FlexASO剪接调节平台旨在生成具有更高效力和更高治疗指数的剪接调节ASOs。QurAlis的ASOs可纠正UNC13A的错误剪接，恢复UNC13A蛋白的生产，并减少可能导致疾病进展的隐秘外显子。 武田口服食欲素受体2激动剂达到2期临床终点 武田（Takeda）公司今天发布了在研疗法TAK-861在治疗1型发作性睡病（NT1）的2b期临床试验中获得的积极结果。TAK-861是一种口服食欲素受体2（OX2R）激动剂。这项随机双盲、含安慰剂对照的临床试验（n=112）达到主要和次要终点。 2b期试验的主要终点显示，在维持清醒测试（MWT）中，所有剂量组与安慰剂组相比在推迟睡眠发生指标上均表现出统计学显著和具有临床意义的改善（p≤0.001）。改善在8周内持续保持。 研究在包括Epworth嗜睡量表（ESS）和每周猝倒发生率（WCR）在内的关键性次要终点方面也取得了一致的结果，相较于安慰剂组，显著改善了主观嗜睡程度和猝倒频率，并在8周内持续保持疗效。试验中大多数NT1患者在8周治疗期结束时的MWT和ESS结果均在正常范围内。 NT1是一种慢性、罕见的中枢神经系统过度嗜睡障碍，由于食欲素神经元的大量丧失，导致大脑和脑脊液中食欲素神经肽水平低下。NT1患者会出现过度白天嗜睡（EDS）、猝倒、夜间睡眠中断、入睡和醒来时的幻觉等症状。这些衰弱症状显著降低生活质量，并严重影响患者工作表现、学业成绩和人际关系。TAK-861旨在通过选择性刺激食欲素受体来解决NT1中的食欲素缺乏问题。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料： [1] Intellia Therapeutics Announces Positive Long-Term Data from Ongoing Phase 1 Study of NTLA-2002, an Investigational In Vivo CRISPR Gene Editing Treatment for Hereditary Angioedema (HAE). Retrieved June 3, 2024, from https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-positive-long-term-data-ongoing [2] Takeda’s TAK-861 Phase 2b Late-Breaking Data Presentations at SLEEP 2024 Demonstrate Clinically Meaningful Impact of Oral Orexin Agonist in Narcolepsy Type 1 Compared to Placebo. Retrieved June 3, 2024, from https://www.takeda.com/newsroom/newsreleases/2024/tak-861-data-at-sleep-2024-on-narcolepsy-type-1/ [3] QurAlis Grants Lilly Exclusive Global License for QRL-204, a Potentially First-in-Class Precision Therapy That Restores UNC13A Function in ALS and FTD. Retrieved June 3, 2024, from https://www.prnewswire.com/news-releases/quralis-grants-lilly-exclusive-global-license-for-qrl-204-a-potentially-first-in-class-precision-therapy-that-restores-unc13a-function-in-als-and-ftd-302156943.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

Takeda pulled back the curtain on a Phase IIb trial evaluating its investigational oral therapy TAK-861 for the treatment of narcolepsy type 1 (NT1). In February, the company said its orexin receptor 2 agonist showed statistically significant and clinically meaningful improvements versus placebo across primary and secondary endpoints in the 112-patient study.The randomised trial assessed the impact of various doses of TAK-861 take once or twice daily on objective and subjective measures of wakefulness over an 8-week treatment period. The primary endpoint showed TAK-861 significantly increased mean sleep latency on the Maintenance of Wakefulness Test (MWT) at week 8 compared to placebo across all dose groups. Mean sleep latency ranged from 16.5 minutes for the lowest 0.5mg/0.5mg dose up to 30.7 minutes for the 2mg/5mg dose, compared to just 7 minutes for placebo.Beefits were seen on key secondary endpoints as well. By week 8, between 66.7% and 95.2% of patients across the TAK-861 dose groups achieved an Epworth Sleepiness Scale (ESS) score ≤10, within the normative range, versus only 19% for placebo. TAK-861 also significantly reduced weekly cataplexy rates, with the twice-daily 2mg/2mg and 2mg/5mg doses reducing median rates down to just 0.7 events per week compared to 4.1 for placebo."The majority of NT1 patients in the trial were found to be within normative ranges for MWT and ESS by the end of the 8-week treatment period as a result of these sustained improvements," Takeda stated. The therapy was also generally well-tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events.Based on the mid-stage data, Takeda plans to advance TAK-861 into global Phase III trials for NT1 in the first half of fiscal year 2024.