MedinCell SA

▎药明康德内容团队编辑 刚刚，美国FDA宣布批准百时美施贵宝（Bristol Myers Squibb）的Cobenfy (xanomeline and trospium chloride，即KarXT）口服胶囊用于治疗精神分裂症成人患者。FDA新闻稿指出，这是靶向胆碱能受体的首个抗精神病药物（antipsychotic drug），长期以来精神分裂症的标准疗法靶向多巴胺受体。该疗法也标志着过去数十年来首个治疗精神分裂症的新机制药物。KarXT在今年初被行业媒体Evaluate评选为2024有望获批的10款潜在重磅疗法之一。 精神分裂症会影响患者如何思考、感觉和行动。其症状包含阳性症状（幻觉、妄想）、阴性症状（难以享受生活、脱离人群）以及认知障碍。这些症状严重影响患者的生活质量和生产力，其中只有10%的病患能够就业、独立生活。与一般大众相比，精神分裂症病患的寿命减少约10-20年。全球约有2100万精神分裂症患者。自抗精神病药物氯丙嗪在1952年首次获批后，目前的标准疗法依然是通过阻断多巴胺受体这一机制来实现。然而许多抗精神病药物的副作用很大。 此次的批准主要是基于EMERGENT项目（评估KarXT治疗精神分裂症的临床项目）的疗效和长期安全性数据。EMERGENT项目包括3项已完成、用以评估KarXT与安慰剂相比的疗效和安全性的EMERGENT-1、EMERGENT-2和EMERGENT-3试验，以及正在进行中、用以评估KarXT长期安全性的EMERGENT-4和EMERGENT-5试验。在所有3项安慰剂对照试验中，KarXT均达到其主要终点，证明与安慰剂相比，患者在阳性和阴性症状量表（PANSS）总分上具有统计学显著和临床意义的降低。通过PANSS阳性、PANSS阴性和PANSS阴性Marder因子子量表（试验的次要终点）测量，KarXT组患者精神分裂症的阳性和阴性症状均减少。 ▲KarXT在EMERGENT-3临床试验中的主要终点结果（图片来源：Karuna公司官网） 此外，KarXT一般具有良好的耐受性，最常见的不良事件是胆碱能性质的，严重程度为轻度至中度。值得一提的是，KarXT与目前可用的抗精神病药物的常见副作用无关，包括体重增加、嗜睡和运动障碍。 KarXT是一款口服M1/M4型毒蕈碱乙酰胆碱受体激动剂，正在开发用于治疗精神和神经系统疾病，包括精神分裂症和痴呆相关精神病性障碍，是首款非靶向多巴胺能与5-羟色胺能信号通路，并具双重机制的新式药物。该疗法原本由Karuna Therapeutics所研发。百时美施贵宝在2023年12月与Karuna达成收购协议，进而囊获此款疗法。再鼎公司拥有这款创新疗法在大中华区的研发权益，它已经在中国获批临床。 KarXT由xanomeline和trospium chloride两种有效成分构成，旨在激活大脑中的毒蕈碱型乙酰胆碱受体的同时，减少对外周毒蕈碱型乙酰胆碱受体的作用。通过刺激毒蕈碱受体M1和M4受体，xanomeline可缓解负面症状，如冷漠、社会驱动力减少、提高认知能力，并对改善其它精神症状，如幻觉和妄想很有帮助。而季铵盐化合物trospium chloride为毒蕈碱受体拮抗剂，可抑制xanomeline于外周神经中的副作用。 ▲Steve Paul博士在2020药明康德全球论坛上分享创新药物开发的洞见 在2020年药明康德全球论坛上，时任Karuna首席执行官的Steve Paul博士曾分享如何加快新药研究步伐的洞见。短短几年后，该公司开发的创新疗法便为全球精神分裂症病患造福。Paul博士曾指出，精神分裂疾病药物领域，自上世纪50年代氯丙嗪被发现以来几乎没有真正的创新，但随着人类对精神病发作和抑郁症生理学信号通路有了更深刻认识，这个情况正在改变。 相关阅读：新药研发的步伐，何时才能告别“循序渐进”？| 药明康德全球论坛 产业界近年积极投入精神分裂症的疗法开发，目前有多款疗法处于临床阶段。梯瓦（Teva Pharmaceuticals）和Medincell在今年5月宣布，其皮下注射奥氮平（olanzapine）缓释注射剂TEV-‘749，在治疗精神分裂症成年患者的3期临床试验SOLARIS中达到主要终点。试验结果显示，治疗8周之后，TEV-‘749显著改善患者的PANSS总分。TEV-‘749采用Medincell专有的共聚合物（copolymer）技术SteadyTeq，只需每月一针，能够稳定、持续地释放奥氮平，这是一种用来治疗精神分裂症的常用第二代抗精神病药物。Neurocrine Biosciences和Nxera Pharma则在上个月共同宣布，其在研疗法NBI-1117568（NBI-'568）在成人精神分裂症患者中进行的2期临床试验获得积极数据。与基线相比，每日一次20 mg的NBI-'568在第6周时在PANSS总分上表现出有临床意义且统计学显著的减少，安慰剂调整后的平均减少值为7.5分（p=0.011）。Neurocrine表示，将于明年年初将这款疗法推进3期临床试验。 Cerevel Therapeutics公司开发的emraclidine是一款M4亚型选择性正向别构调节剂（PAM），在治疗精神分裂症患者的1b期临床试验中显示出良好的疗效和安全性。去年12月，艾伯维（AbbVie）公司斥资约87亿美元收购了Cerevel。目前emraclidine正在两项2期临床试验中接受检验，初步数据预计在今年11月发布。而MapLight Therapeutics公司的在研疗法ML-007/PAC则是一款由毒蕈碱乙酰胆碱受体M1和M4亚型的激动剂和外周作用的乙酰胆碱受体拮抗剂构成的组合疗法，正在1期临床试验中用于治疗精神分裂症和阿尔茨海默病患者的精神病发作。 了解更多FDA获批新药 请点击下图访问我们的小程序 ▲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] FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia. Retrieved September 26, 2024 from https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia [2] Karuna Therapeutics Submits New Drug Application to U.S. Food and Drug Administration for KarXT for the Treatment of Schizophrenia. Retrieved September 28, 2023 from https://investors.karunatx.com/news-releases/news-release-details/karuna-therapeutics-submits-new-drug-application-us-food-and 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

MONTPELLIER, France--( BUSINESS WIRE )-- New data presented by Teva at ECNP 2024 * demonstrate switching to UZEDY at four weeks after the last dose of once-monthly Perseris ® (RBP-7000) provided the most comparable pharmacokinetic (PK) profile based on relevant simulations, with comparable doses identified. Perseris manufacturer announced in July 2024 the discontinuation of its commercialization. Teva already presented in June 2024 data informing clinical strategies for switching patients to UZEDY from a once-monthly intramuscular injection of Invega Sustenna ® (paliperidone palmitate) ** . Richard Malamut, Chief Medical Officer of Medincell said: “We are delighted to see that our partner is fully committed to supporting healthcare providers in implementing effective switching strategies to UZEDY, which offers several key differentiating features compared to other risperidone or paliperidone palmitate formulations: no loading doses or oral supplementation at initiation, flexible dosing intervals of either one or two months, subcutaneous administration, ready-to-use prefilled syringe.” About additional results from the Advance study on the utilization of long-acting injectable antipsychotics, which were also reported by Teva at ECNP 2024, Richard Malamut said: “ It is encouraging to see that most of the factors raised by patients with Schizophrenia, their caregivers, and healthcare providers regarding use of a long-acting injectable antipsychotic can be effectively addressed with UZEDY.” ACCESS HERE THE COMPLETE PRESS RELEASE * 37 th Annual European College of Neuropsychopharmacology (ECNP) Congress - September 21-24, 2024, Milan, Italy. www.ecnp.eu ** Medincell’s press release, June 3 rd , 2024: https://www.medincell.com/wp-content/uploads/2024/06/PR_MDC_Elevate2024_EN_vf.pdf About Medincell Medincell is a clinical- and commercial-stage biopharmaceutical licensing company developing long-acting injectable drugs in many therapeutic areas. Our innovative treatments aim to guarantee compliance with medical prescriptions, to improve the effectiveness and accessibility of medicines, and to reduce their environmental footprint. They combine active pharmaceutical ingredients with our proprietary BEPO ® technology which controls the delivery of a drug at a therapeutic level for several days, weeks or months from the subcutaneous or local injection of a simple deposit of a few millimeters, entirely bioresorbable. The first treatment based on BEPO ® technology, intended for the treatment of schizophrenia, was approved by the FDA in April 2023, and is now distributed in the United States by Teva under the name UZEDY ® (BEPO ® technology is licensed to Teva under the name SteadyTeq™). We collaborate with leading pharmaceutical companies and foundations to improve global health through new treatment options. Based in Montpellier, Medincell currently employs more than 140 people representing more than 25 different nationalities. UZEDY ® and SteadyTeq™ are trademarks of Teva Pharmaceuticals www.medincell.com

MONTPELLIER, France--( BUSINESS WIRE )-- New data presented by Teva at ECNP 2024 * demonstrate switching to UZEDY at four weeks after the last dose of once-monthly Perseris ® (RBP-7000) provided the most comparable pharmacokinetic (PK) profile based on relevant simulations, with comparable doses identified. Perseris manufacturer announced in July 2024 the discontinuation of its commercialization. Teva already presented in June 2024 data informing clinical strategies for switching patients to UZEDY from a once-monthly intramuscular injection of Invega Sustenna ® (paliperidone palmitate) ** . Richard Malamut, Chief Medical Officer of Medincell said: “We are delighted to see that our partner is fully committed to supporting healthcare providers in implementing effective switching strategies to UZEDY, which offers several key differentiating features compared to other risperidone or paliperidone palmitate formulations: no loading doses or oral supplementation at initiation, flexible dosing intervals of either one or two months, subcutaneous administration, ready-to-use prefilled syringe.” About additional results from the Advance study on the utilization of long-acting injectable antipsychotics, which were also reported by Teva at ECNP 2024, Richard Malamut said: “ It is encouraging to see that most of the factors raised by patients with Schizophrenia, their caregivers, and healthcare providers regarding use of a long-acting injectable antipsychotic can be effectively addressed with UZEDY.” ACCESS HERE THE COMPLETE PRESS RELEASE * 37 th Annual European College of Neuropsychopharmacology (ECNP) Congress - September 21-24, 2024, Milan, Italy. www.ecnp.eu ** Medincell’s press release, June 3 rd , 2024: https://www.medincell.com/wp-content/uploads/2024/06/PR_MDC_Elevate2024_EN_vf.pdf About Medincell Medincell is a clinical- and commercial-stage biopharmaceutical licensing company developing long-acting injectable drugs in many therapeutic areas. Our innovative treatments aim to guarantee compliance with medical prescriptions, to improve the effectiveness and accessibility of medicines, and to reduce their environmental footprint. They combine active pharmaceutical ingredients with our proprietary BEPO ® technology which controls the delivery of a drug at a therapeutic level for several days, weeks or months from the subcutaneous or local injection of a simple deposit of a few millimeters, entirely bioresorbable. The first treatment based on BEPO ® technology, intended for the treatment of schizophrenia, was approved by the FDA in April 2023, and is now distributed in the United States by Teva under the name UZEDY ® (BEPO ® technology is licensed to Teva under the name SteadyTeq™). We collaborate with leading pharmaceutical companies and foundations to improve global health through new treatment options. Based in Montpellier, Medincell currently employs more than 140 people representing more than 25 different nationalities. UZEDY ® and SteadyTeq™ are trademarks of Teva Pharmaceuticals www.medincell.com