5-HT1D receptor

▎药明康德内容团队编辑 日前，Satsuma Pharmaceuticals宣布，美国FDA已接受其在研鼻腔喷雾剂STS101重新提交的新药申请（NDA），用于急性治疗伴或不伴先兆的偏头痛。该申请的PDUFA日期为2025年4月30日。 偏头痛是神经内科常见疾病之一，虽然不是致命的疾病，但是每当发作时，患者十分痛苦并严重影响生活。双氢麦角胺是一种非选择性5羟色胺1受体激动剂，可以非选择性的刺激5羟色胺1受体，从而阻止急性偏头痛的发生。其药理机制是通过阻止神经源性炎症、中枢敏感化、神经肽释放发挥功能。鼻腔喷雾剂给药具有靶向、高效、速效、毒副作用小的特点，相比其他给药方式，具有使用简便，起效快的优势。 STS101新药申请主要基于两项临床试验的结果支持：一是于2021年6月完成的1期药代动力学和安全性试验，二是ASCEND临床3期长期开放标签安全性试验。在ASCEND试验中，446名受试者总共使用了一万多剂STS101，治疗了超过9000次偏头痛发作，试验持续时间最长达18个月。 图片来源：123RF 该申请中亦包含了1600名受试者参与的双盲、安慰剂对照的SUMMIT临床3期疗效试验的结果。分析显示，STS101在使用后超过2小时的所有时间点（3、4、6、12、24和48小时）上表现出显著且持久的疗效（p<0.001）。此外，STS101在多个次要终点上也表现出显著且持久的抗偏头痛效果，这些终点均符合FDA当前指导文件和国际头痛学会（IHS）关于急性偏头痛发作治疗对照试验指南中的相关建议。 在之前的完整回复函（CRL）中，FDA并未对STS101的临床试验结果或安全性提出质疑，也未要求进行额外的临床试验。然而，FDA提出了关于化学、生产和控制（CMC）方面的意见。 STS101是一种用于急性治疗偏头痛的创新在研疗法。基于已广泛使用的抗偏头痛药物甲磺酸二氢麦角胺（DHE），通过Satsuma专有的鼻部递送设备给药。STS101的设计旨在为患者提供快速且便捷的自我给药方式。Satsuma的鼻用粉末DHE制剂已显示出快速达到血浆药物浓度峰值，血浆药物浓度持续时间长以及多次给药之间差异性低等特点。 ▲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] Satsuma Pharmaceuticals and SNBL Receive FDA Acceptance of NDA Resubmission of STS101 for the Acute Treatment of Migraine With or Without Aura. Retrieved November 27, 2024 from https://www.prnewswire.com/news-releases/satsuma-pharmaceuticals-and-snbl-receive-fda-acceptance-of-nda-resubmission-of-sts101-for-the-acute-treatment-of-migraine-with-or-without-aura-302316089.html [2] Satsuma Pharmaceuticals and SNBL Resubmits the New Drug Application for STS101 (Dihydroergotamine Nasal Powder) for the Acute Treatment of Migraine With or Without Aura. Retrieved November 27, 2024 from https://investors.satsumarx.com/2024-10-30-Satsuma-Pharmaceuticals-and-SNBL-Resubmits-the-New-Drug-Application-for-STS101-Dihydroergotamine-Nasal-Powder-for-the-Acute-Treatment-of-Migraine-With-or-Without-Aura [3] Satsuma Pharmaceuticals and SNBL Receive FDA Acceptance of NDA Resubmission of STS101 for the Acute Treatment of Migraine With or Without Aura. Retrieved November 27, 2024 from https://investors.satsumarx.com/2024-11-26-Satsuma-Pharmaceuticals-and-SNBL-Receive-FDA-Acceptance-of-NDA-Resubmission-of-STS101-for-the-Acute-Treatment-of-Migraine-With-or-Without-Aura 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

▎药明康德内容团队编辑 推进猪肾脏移植进入临床试验，eGenesis完成1.91亿美元融资 eGenesis今日宣布完成1.91亿美元的D轮融资。获得资金将用于推进该公司的核心在研产品EGEN-2784进入首个人体肾脏移植临床试验，同时也将用于推进其他管线项目并扩大生产规模。 全球数百万人患有终末期肾病或肾功能衰竭，这是一种危及生命的疾病。肾移植被认为是改善生活质量和治疗效果的最佳选择。然而，器官的需求远远超过供应，目前有超过9万人等待肾脏移植，而每年仅约2万5千例肾移植手术得以实施。 eGenesis开发的人类兼容性供体器官有望成为一种可行的替代方案，以缓解可移植器官的短缺问题。该公司的EGEN-2784是用于肾移植的核心在研产品，包含三类基因编辑：敲除三个参与糖抗原合成、与超急性排斥反应相关的基因；插入七个与调节排斥反应的信号通路相关的人类转基因，这些通路涉及炎症、先天免疫、凝血和补体；使猪体内中的内源性逆转录病毒失活。2024年3月，eGenesis宣布成功完成世界首例将猪肾脏移植到活体患者体内的手术。 FDA接受偏头痛小分子疗法的新药申请 Axsome Therapeutics今日宣布，美国FDA接受该公司为在研疗法AXS-07重新递交的新药申请（NDA），用于急性治疗偏头痛。FDA预计将在2025年1月31日之前完成审评。 AXS-07是一种口服、快速吸收的多机制在研药物，用于急性治疗偏头痛。该药物由基于Axsome公司的MoSEIC技术平台改造的meloxicam和rizatriptan组成。MoSEIC能够在延长meloxicam半衰期的同时实现快速吸收。Meloxicam是一种COX-2偏向型非甾体抗炎药，rizatriptan则是一种5-HT 1B/1D激动剂。AXS-07旨在提供快速、效力增强且具有一致性的偏头痛缓解效果，并减少症状复发。 苯丙酮尿症潜在“first-in-class”疗法挺进3期临床 Jnana Therapeutics今日公布了其在研疗法JNT-517治疗苯丙酮尿症（PKU）成人患者的1/2期临床试验中的第二剂量组（150 mg，每日两次）的试验结果。数据显示，75 mg和150 mg组均显示出具有临床意义、统计学上显著的疗效。JNT-517是一种针对苯丙氨酸（Phe）转运蛋白SLC6A19的小分子抑制剂，为潜在“first-in-class”口服疗法，适用于所有年龄段和基因型的PKU患者。基于这些积极结果，该公司计划在2025年初启动关键性3期临床试验，评估JNT-517治疗PKU的效果。 今日公布的150 mg组数据基于18名参与者，其中11人服用JNT-517，7人服用安慰剂，历时28天。结果显示： JNT-517在第14、21、28天将患者平均血液Phe水平较基线降低了60%（p<0.0001）。相比之下，之前研究的75 mg剂量组在相同时间段内的平均血液Phe水平降低了44%。 患者在用药开始后7天内观察到快速的疗效，血液Phe水平显著降低，并在28天的用药期间持续维持。 无论基线Phe水平或之前的PKU治疗史如何，所有参与者均表现出显著的疗效。 JNT-517耐受性良好，无严重不良事件，无临床显著的实验室参数变化，除Phe外，未观察到血液氨基酸的临床显著变化，与75 mg剂量组和1a期健康志愿者研究的安全性一致。 ▲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] Jnana Therapeutics Presents New Positive Data from Phase 1/2 Study of JNT-517 in Individuals with Phenylketonuria – Results Support Planned Pivotal Study in Early 2025. Retrieved September 4, 2024, from https://www.globenewswire.com/news-release/2024/09/04/2940409/0/en/Jnana-Therapeutics-Presents-New-Positive-Data-from-Phase-1-2-Study-of-JNT-517-in-Individuals-with-Phenylketonuria-Results-Support-Planned-Pivotal-Study-in-Early-2025.html [2] Axsome Therapeutics Announces FDA Acceptance of NDA Resubmission for AXS-07 for the Acute Treatment of Migraine. Retrieved September 4, 2024, from https://www.globenewswire.com/news-release/2024/09/04/2940340/33090/en/Axsome-Therapeutics-Announces-FDA-Acceptance-of-NDA-Resubmission-for-AXS-07-for-the-Acute-Treatment-of-Migraine.html [3] eGenesis Raises $191 Million Series D Financing to Advance Lead Program for Kidney Transplant. Retrieved September 4, 2024, from https://egenesisbio.com/press-releases/egenesis-raises-191-million-series-d-financing-to-advance-lead-program-for-kidney-transplant/ 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

Pictured: FDA signage outside its headquarters/iStock, JHVEPhoto The FDA has rejected Satsuma Pharmaceuticals’ investigational dihydroergotamine nasal powder product STS101 for the treatment of acute migraine, according to parent company Shin Nippon Biomedical Laboratories‘ press release posted Thursday. The regulator’s Complete Response Letter (CRL) pointed to problems with STS101’s chemistry, manufacturing and controls. Satsuma will discuss the rejection with the FDA, building toward a resubmission for the nasal drug. SNBL’s Japan-listed stock dropped around 12% Thursday in response to the news, according to Reuters. The CRL did not identify safety issues with STS101, nor did it ask Shin Nippon Biomedical Laboratories (SNBL) to conduct additional studies, according to an Endpoints News. STS101 is a reformulated version of dihydroergotamine mesylate (DHE), a well-established migraine medication for nasal-route administration. The drug candidate also utilizes Satsuma’s proprietary device for delivery. Compared with existing acute migraine treatments, STS101 is designed to be more convenient and allows for self-administration, according to Satsuma’s website. It also has more rapid absorption and more quickly reaches peak DHE plasma levels as compared with liquid nasal spray formulations, which in turn could translate to better efficacy, the company contends. Satsuma backed its New Drug Application for STS101, which the FDA accepted in May 2023, with data from the Phase III ASCEND study, which gave more than 10,500 doses of STS101 over 18 months to 446 enrolled patients. In September 2022, long-term data from ASCEND demonstrated that at two hours after treatment, STS101 could elicit freedom from pain and from the most bothersome symptom in 34.2% and 53.4% of all treated migraine attacks, respectively. The drug candidate also eliminated the need for rescue medications in 94% of treated attacks. In terms of safety, ASCEND found no clinically relevant systemic findings or unexpected treatment-related serious adverse events. Most toxicities were mild and transient. Also included in Satsuma’s data package for STS101 is the Phase III SUMMIT trial, which failed its primary efficacy bar. The company reported in November 2022 that in SUMMIT, STS101 could not significantly distinguish itself from placebo in terms of freedom from pain and from the most bothersome symptom two hours post-treatment. At the time, the company announced that it had no plans to independently commercialize STS101 and would instead look for alternatives that would “maximize value for shareholders, while minimizing cash expenditures.” Satsuma began in 2016 and STS101 is its only asset so far. In March 2023, following the rocky development road for STS101 and in order to cut back on costs, Satsuma announced that it would lay off approximately 36% of its staff. A few weeks later, SNBL announced that it would acquire Satsuma. 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.