Vanzacaftor/Tezacaftor/Deutivacaftor

▎药明康德内容团队编辑 Vertex Pharmaceuticals今天宣布，美国FDA已接受其每日一次vanzacaftor/tezacaftor/deutivacaftor三联疗法（vanza三联疗法）治疗6岁及以上的囊性纤维化（CF）患者的新药申请（NDA），这些患者至少带有F508del突变或囊性纤维化跨膜传导调节器（CFTR）基因中的另一个应答性突变。带有这些突变的患者对vanza三联疗法产生应答。Vertex对此申请使用了优先审评券，PDUFA的目标日期为2025年1月2日。此外，欧洲药品管理局（EMA）也完成Vertex在欧盟提交该疗法针对6岁及以上CF患者的上市许可申请（MAA）的验证。该公司也已在加拿大、澳大利亚、瑞士和英国提交了监管申请。 分析显示，vanza三联疗法在三项3期临床试验中获得积极结果。在名为SKYLINE 102和SKYLINE 103的随机双盲，含活性对照的3期临床试验中，在随机分组前，患者接受了4周获批疗法Trikafta初始治疗，以建立预测的一秒用力呼气量百分比（ppFEV1）、汗液氯化物（SwCl）及其他疗效参数的基线值。然后患者随机接受Trikafta或vanza三联疗法的治疗。 试验结果显示，接受治疗24周后，基于ppFEV1数值的评估，vanza三联疗法的疗效与活性对照药物相当，达到试验的主要终点。 ▲Vanza三联疗法在SKYLINE 102和SKYLINE 103中达到主要终点（图片来源：Vertex公司官网） SKYLINE 102和SKYLINE 103中的关键次要终点包括与活性对照药物相比，第24周与基线相比的SwCl绝对变化，SwCl低于60 mmol/L的患者比例，以及SwCl低于30 mmol/L的患者比例。 试验结果显示，vanza三联疗法在SKYLINE 102和SKYLINE 103的第一个关键次要终点上，在降低SwCl水平方面表现出优效性。 ▲Vanza三联疗法与活性对照药物相比，在降低SwCl水平方面表现出优效性（图片来源：Vertex官网） 在第二和第三个关键次要终点上，vanza三联疗法也表现出优效性。其他次要终点的结果与主要终点和关键次要终点的结果一致。此外，52周的结果与24周的结果一致。 在RIDGELINE 105研究中，6-11岁儿童也遵循了相同的方案，先接受至少4周的Trikafta治疗以建立基线值，然后再接受vanza三联疗法治疗。这项研究主要关注的是安全性。在所有三项研究中，vanza三联疗法耐受性良好，与活性对照药物治疗组的安全性特征相似。此外，vanza三联疗法在6至11岁的儿童中的安全性与12岁及以上人群中的安全性类似。 在CF患者中，CFTR基因的突变导致细胞表面CFTR蛋白通道的数量和/或功能减少。Vanzacaftor和tezacaftor旨在通过促进CFTR蛋白的加工和运输，增加细胞表面CFTR蛋白数量的校正剂。Deutivacaftor是一种增效剂，旨在增加送达细胞表面的CFTR蛋白的通道开放概率，以改善细胞膜上盐和水的流动。这款三联疗法已经获得美国FDA授予的快速通道资格和孤儿药资格。 ▲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] Vertex Announces FDA Acceptance of New Drug Application for Vanzacaftor/Tezacaftor/Deutivacaftor, a Next-In-Class Triple Combination Treatment for Cystic Fibrosis. Retrieved July 2, 2024 from https://www.businesswire.com/news/home/20240702676594/en 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

- Vanza triple granted priority review with Prescription Drug User Fee Act (PDUFA) target action date of January 2, 2025 – - EU Marketing Authorization Application (MAA) submission also validated by European Medicines Agency (EMA) BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for investigational once-daily vanzacaftor/tezacaftor/deutivacaftor triple combination therapy (vanza triple) for people living with cystic fibrosis (CF) ages 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsive to the vanza triple. Vertex used a priority review voucher for this submission reducing the review time from 10 months to 6 months, resulting in a Prescription Drug User Fee Act (PDUFA) target action date of January 2, 2025. “The FDA acceptance of our vanza triple application and the MAA validation by the EMA represent important milestones in the decades-long development of CFTR modulators and another example of our track record of serial innovation in CF,” said Nia Tatsis, Ph.D., Executive Vice President, Chief Regulatory and Quality Officer at Vertex. “Vanzacaftor raises the high bar set by TRIKAFTA® and gives more people with CF the chance to get to levels of sweat chloride below the diagnostic threshold for CF, and even to levels of sweat chloride seen in those without CF.” Vertex also received validation of its Marketing Authorization Application (MAA) submission by the European Medicines Agency (EMA) in the EU for patients ages 6 years and older. The company has also submitted in Canada, Australia, Switzerland and the U.K. About Cystic Fibrosis Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving. Today Vertex CF medicines are treating over 65,000 people with CF across 60 countries on six continents. This represents 2/3 of the diagnosed people with CF eligible for CFTR modulator therapy. Diagnosis of CF is often made by genetic testing and is confirmed by testing sweat chloride (SwCl), which measures CFTR protein dysfunction. The diagnostic threshold for CF is SwCl ≥60 mmol/L, while levels between 30-59 indicate CF is possible and more testing may be needed to make the diagnosis of CF. A SwCl level of <30 mmol/L is seen in people who carry one copy of a CFTR gene mutation but do not have any manifestation of disease (carriers). Higher levels of SwCl are associated with more severe disease. Restoring CFTR function leads to lower levels of SwCl. SwCl levels below 60 mmol/L are associated with improved outcomes such as better and more stable lung function, fewer pulmonary exacerbations, better quality of life and improved survival. Restoring SwCl levels below 30 mmol/L has long been the ultimate treatment goal for Vertex, as levels below 30 mmol/L are considered normal and are typical of CF carriers who do not have disease. About vanzacaftor/tezacaftor/deutivacaftor (the “vanza triple”) In people with CF, mutations in the CFTR gene lead to decreased quantity and/or function of the CFTR protein channel at the cell surface. Vanzacaftor and tezacaftor are designed to increase the amount of CFTR protein at the cell surface by facilitating the processing and trafficking of the CFTR protein. Deutivacaftor is a potentiator designed to increase the channel open probability of the CFTR protein delivered to the cell surface to improve the flow of salt and water across the cell membrane. Investigational vanzacaftor/tezacaftor/deutivacaftor was granted Fast Track and Orphan Drug Designations from the U.S. Food and Drug Administration for the treatment of cystic fibrosis. The vanza triple will be subject to a meaningfully lower single-digit royalty obligation, compared to the rate payable on Vertex’s current CF portfolio. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X. Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, the statements by Nia Tatsis, Ph.D., in this press release, and statements regarding our expectations for the benefits of and potential for the vanza triple, and our expectations that the vanza triple will be subject to a lower single-digit royalty obligation. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy, and other reasons, that future competitive or other market factors may adversely affect the commercial potential for the vanza triple, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at and available through the company's website at . You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN)