Ivacaftor deuterated

- Deutivacaftor/tezacaftor/vanzacaftor approved for people with cystic fibrosis 6 years and older with at least one responsive mutation in the CFTR gene, including additional mutations not previously approved with other CFTR modulator therapies - - In head-to-head clinical trials, deutivacaftor/tezacaftor/vanzacaftor was non-inferior on ppFEV1 and further decreased sweat chloride compared to ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor - LONDON --(BUSINESS WIRE)--Mar. 7, 2025-- Vertex Pharmaceuticals (Nasdaq: VRTX) announced today that the United Kingdom ( UK ) Medicines and Healthcare products Regulatory Agency (MHRA) has granted approval for ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor), a once-daily next-in-class triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment 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 CFTR gene. “For more than 20 years we have been focused on discovering medicines that treat the underlying cause of the disease with the goal of helping people live longer and better lives. The approval of ALYFTREK, our fifth CFTR modulator regimen, represents another significant milestone in that journey for people with CF in the UK,” said Carmen Bozic , M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex . “The deutivacaftor/tezacaftor/vanzacaftor Phase 3 trial results showed that it is possible to further improve CFTR protein function with this once-a-day, more flexible and less burdensome regimen,” said Professor Alex Horsley , Professor of Respiratory Medicine at the University of Manchester, UK . “Children and adults taking the new triple combination therapy were more likely to have carrier levels of sweat chloride compared to those on the ivacaftor/tezacaftor/elexacaftor regimen, which we hope will translate to reduced risk of developing CF-related complications in the long term.” Vertex is working with the National Institute for Health and Care Excellence (NICE) and the NHS to ensure eligible patients can access this new therapy, which treats the underlying cause of CF, as soon as possible. This medicine was approved for patients ages 6 years and older by the U.S. FDA in December 2024 and Marketing Authorization Applications are ongoing with the European Medicines Agency (EMA) and the regulatory authorities in Canada , Switzerland , Australia and New Zealand in the same age group. About Cystic Fibrosis Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 94,000 people in North America , Europe and Australia . 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 68,000 people with CF across more than 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 ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor) 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. ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor) is approved in the UK for the treatment of CF in patients aged 6 years and older who have at least one F508del mutation or another responsive mutation in the CFTR gene. For complete product information, please see the Summary of Product Characteristics that can be found on https://products.mhra.gov.uk/. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. 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 neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1. 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 15 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. Vertex 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 Carmen Bozic , M.D., and Professor Alex Horsley , in this press release, and statements regarding expectations for and the anticipated benefits of ALYFTREK, Vertex’s work with NICE and the NHS to ensure eligible patients can access this new therapy as soon as possible, and the status of the Marketing Authorization Applications for ALYFTREK with global regulatory authorities. While we believe 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, 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 www.sec.gov and available through the company's website at www.vrtx.com. 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) View source version on businesswire.com: https://www.businesswire.com/news/home/20250228599468/en/ Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com Media: mediainfo@vrtx.com or International: +44 20 3204 5275 Source: Vertex Pharmaceuticals Incorporated

关注并星标CPHI制药在线 2025年预计有多款里程碑式的疗法将获得FDA的批准，并有可能获得良好的商业回报。例如Vertex的囊性纤维化药物Alyftrek，已于去年年底获得批准，预计将在2030年实现80亿美元以上的年销售额。阿斯利康和第一三共的乳腺癌ADC药物Datroway于今年1月获得FDA批准，有望在2030年达到50亿美元的年销售额高度。 一、Alyftrek (vanzacaftor/tezacaftor/deutivacaftor) ●开发商：Vertex　　 ●模态：小分子　　 ●适应症：囊性纤维化　　 ●监管状态：已批准（2024年12月20日）　　 ●预测2030年销售额：83.4亿美元　　 ●背景与意义： Alyftrek代表着一种崭新的三重组合 CFTR 调节剂疗法：vanzacaftor、tezacaftor 和 deutivacaftor，适用于6岁及以上携带至少一个对该疗法有反应突变的囊性纤维化（CF）患者。囊性纤维化是由CFTR基因突变引起的，这个基因负责CFTR蛋白质的生成，基因突变导致这种蛋白质功能障碍或缺失，从而导致体内产生异常粘稠的粘液，积聚在器官中，引发大多数CF症状。CFTR调节剂可以改善那些由CFTR基因中特定突变引起的囊性纤维化患者的CFTR蛋白功能。Alyftrek为CF患者提供了崭新的选择，特别是对于无法耐受Trikafta（同样为Vertex产品）的患者。除此之外，Alyftrek只需每日服用一次，相较于其他调节剂每日两次的服用方案，可能使患者的用药更加便利。 二、Datroway (datopotamab deruxtecan) ●开发商：阿斯利康/第一三共　　 ●模态：ADC　　 ●适应症：既往接受过治疗的转移性 HR 阳性、HER2 阴性乳腺癌　　 ●监管状态：已批准（2025年1月17日）　　 ●预测2030年销售额：49.8亿美元　　 ●背景与意义：  美国每年新检测出的乳腺癌患者超过30万人。虽然早期乳腺癌的生存率较高，但转移性患者存活时间超过5年的比例只有30%。大约70%的乳腺癌确诊病例属于HR阳性、HER2阴性乳腺癌。HR阳性转移性乳腺癌的早期治疗中，内分泌疗法被广泛使用。然而，初步治疗后，内分泌治疗的疗效通常有限。目前在内分泌治疗后的标准治疗是化疗，但化疗的反应率和治疗效果较差。在这样的情况下，Datroway的获批显得意义非常重大。Datroway用于治疗无法手术切除或转移性HR阳性、HER2阴性乳腺癌的成人患者，这些患者已接受过内分泌疗法和化疗的治疗。这种新型的TROP2靶向ADC药物的批准标志着一个重要的治疗里程碑，为转移性乳腺癌患者提供了常规化疗之外的新选择。 三、Nivolumab Enhanze ●开发商：百时美施贵宝　　 ●模态：单抗　　 ●适应症：多发性硬化症　　 ●监管状态：已递交申请（PDUFA日期2025年2月28日）　　 ●预测2030年销售额：39.1亿美元　　 ●背景与意义： Halozyme与Bristol Myers Squibb合作，已提交Opdivo® (nivolumab) 与 Enhanze® 联合制剂的BLA申请，用于治疗多发性硬化症 (MS)。Opdivo 是BMS的王牌PD-1 免疫检查点抑制剂。该药物利用 Halozyme 的 Enhanze® 技术来改善药物输送。Enhanze®通过提高药物的皮下给药效率，改善患者的治疗体验。该技术的核心是利用重组人透明质酸酶PH20（rHuPH20）来分解皮下组织中的透明质酸，透明质酸是皮肤和结缔组织中的一种天然屏障物质。通过暂时降低透明质酸的粘性，Enhanze® 技术能够加速皮下药物的吸收，使大分子药物更快、更高效地进入血液循环。这种方式不仅可以减少药物给药时间，改善患者的舒适度，还能在某些情况下减少静脉注射的需求，使得许多原本需要通过静脉注射的药物可以通过皮下注射给药。 四、Journavx (suzetrigine) ●开发商：Vertex　　 ●模态：小分子　　 ●适应症：中度至重度急性疼痛　　 ●监管状态：已批准（2025年1月30日）　　 ●预测2030年销售额：29亿美元　　 ●背景与意义： Vertex的Journavx（suzetrigine）获得FDA批准，用于治疗成人中度至重度急性疼痛，成为近20年来首个非阿片类镇痛药。Journavx通过阻断NaV1.8钠离子通道发挥作用，这一新机制标志着疼痛治疗领域的重要突破。与传统阿片类药物不同，它不具有成瘾性，并且在临床试验中显示出与阿片类药物相当的止痛效果，但副作用较少。 Journavx的成功推动了NaV1.8抑制剂的进一步开发，目前有多个候选药物正在进行临床试验。尽管NaV1.7和NaV1.8钠通道一直被认为是疼痛治疗的潜在靶点，但开发具有高度选择性的药物一直面临挑战，特别是由于这些通道在其他组织中具有高度同源性。Journavx的选择性优势使其在不影响其他身体功能的前提下有效缓解疼痛。 未来，Journavx及其同类药物有望取代阿片类药物，解决长期困扰的成瘾性问题，同时在急性和慢性疼痛治疗领域发挥更大作用。 五、Brensocatib ●开发商：Insmed　　 ●模态：小分子　　 ●适应症：非囊性纤维化支气管扩张　　 ●监管状态：已递交NDA申请（PDUFA日期2025年8月12日）　　 ●预测2030年销售额：28.4亿美元　　 ●背景与意义： 尽管非囊性纤维化支气管扩张（支气管扩张症）的患病率近年来有所增加，但它仍被广泛忽视。患者常表现出慢性咳嗽、痰液产生以及反复的呼吸道感染和加重发作，这些症状严重影响患者的生活质量并增加住院风险。支气管扩张症的病因复杂，病情表现和严重程度因人而异，这种异质性给临床管理带来了巨大挑战。尽管目前患者可以使用一些现有的治疗方法，但FDA和EMA尚未批准任何针对支气管扩张症的专门药物。当前的管理措施主要集中在清理气道、使用黏液活性剂和抗生素治疗急性发作，而长期使用抗生素则面临耐药性问题。目前正在进行的 3 期 ASPEN 试验是支气管扩张症领域规模最大的全球研究，旨在评估 Brensocatib 对支气管扩张症加重发作率的影响。 Brensocatib 是一种口服的选择性 DPP-1 （二肽基肽酶1）抑制剂，可作为中性粒细胞介导疾病（包括支气管扩张和无鼻息肉的慢性鼻窦炎）的潜在治疗方法。如果获得FDA批准，将成为首 款支气管扩张症专用药物。 六、Aficamten ●开发商：Cytokinetics ●模态：小分子 ●适应症：阻塞性肥厚型心肌病 ●监管状态：已递交NDA申请（PDUFA日期9月26日） ●预测2030年销售额：26亿美元 ●背景与意义： 肥厚型心肌病（HCM）是最常见的单基因心脏疾病，估计大约影响1/500的人口。其主要由肌节的染色体显性突变引起，其中β-心脏肌球蛋白（MYH7）和心脏肌球蛋白结合蛋白C（cMYBP-C, MYBPC3）的突变占据了约50%的家族性HCM病例。Ficamten是一种选择性的小分子心脏肌球蛋白抑制剂，通过显著减缓磷酸盐释放，降低ATP酶活性，稳定肌球蛋白与肌动蛋白的弱结合状态。Aficamten具备成为治疗肥厚型心肌病有效药物的潜力。 七、Tolebrutinib ●开发商：赛诺菲　　 ●模态：小分子　　 ●适应症：非复发性继发进展型多发性硬化症　　 ●监管状态：III期试验HERCULES于2024年9月实现主要终点　　 ●预测2030年销售额：13.7亿美元　　 ●背景与意义： FDA已于2024年12月13日授予tolebrutinib突破性疗法认定，用于治疗非复发性继发进展型多发性硬化症（nrSPMS）成人患者。与安慰剂相比，Tolebrutinib能将6个月确认的残疾进展（CDP）的发生时间延缓31%（HR 0.69；95% CI 0.55-0.88；p=0.0026）。Tolebrutinib是首个能够穿透大脑的BTK抑制剂，在多发性硬化症领域获得了突破性疗法认定。目前对于非复发性继发进展型多发性硬化症（nrSPMS）尚无获批药物。 八、Remibrutinib ●开发商：诺华　　 ●模态：小分子　　 ●适应症：慢性自发性荨麻疹（CSU）　　 ●监管状态：预计2025年初递交NDA申请　　 ●预测2030年销售额：13亿美元　　 ●背景与意义： CSU指持续 6 周或更长时间的慢性荨麻疹，影响全球约 4000 万人。其特征是突然出现瘙痒的荨麻疹或深层组织肿胀（血管性水肿，可发生在面部、喉咙、手和脚上）。CSU 会引起严重的情绪困扰，大多数患者睡眠不足，焦虑或抑郁等精神障碍发生率很高，并且会影响他们的工作效率。抗组胺药通常用于治疗 CSU，因为它们可以阻断组胺受体并阻止组胺的促炎作用，从而导致瘙痒和肿胀。然而，超过 50% 的 CSU 患者无法单靠 H1 抗组胺药来控制。 诺华的BTK抑制剂remibrutinib在关键的 III 期研究 REMIX-1 和 REMIX-2 中显示出显著的症状改善能力。Remibrutinib是一款高选择性共价口服 BTK 抑制剂，可阻断 BTK 级联并防止引起瘙痒性荨麻疹和肿胀的组胺释放。除了 CSU，remibrutinib还在其他几种免疫介导疾病中进行研究，例如化脓性汗腺炎，它在 II 期研究中达到了主要终点。 九、Depemokimab ●开发商：GSK　　 ●模态：单抗　　 ●适应症：伴有 2 型炎症的哮喘以及慢性鼻窦炎伴鼻息肉 (CRSwNP)　　 ●监管状态：临床III期，向EMA递交申请　　 ●预计2030年销售额：11.3亿美元　　 ●背景与意义： 在欧洲估计有超过 4200 万人患有哮喘，给患者的生活和医疗资源带来了沉重的负担，估计每年的社会成本为 460 亿欧元。CRSwNP（慢性鼻窦炎伴鼻息肉）是一种慢性疾病，影响多达 4% 的普通人群。 Depemokimab 是一种针对白细胞介素 5 (IL-5) 的单抗，是首个针对2型炎症哮喘和CRSwNP进入III 期试验的超长效生物制剂。Depemokimab 作为 2 型炎症哮喘患者的附加疗法，降低了病情恶化和住院率；与安慰剂相比，depemokimab 可减小鼻息肉大小和减少鼻塞。研究结果支持六个月 (26 周) 的给药方案。在哮喘患者和 CRSwNP 患者中，临床试验表明 depemokimab 可以持续抑制疾病的关键驱动因素，每年仅注射两次。 十、Penmenvy (MenABCWY) ●开发商：GSK ●模态：疫苗 ●适应症：五合一脑膜炎疫苗 ●监管状态：已获批（2025年2月14日） ●预计2030年销售额：12.4亿美元 ●背景与意义： 2025年2月18日， FDA批准了新的5合1疫苗Penmenvy，用于预防10至25岁人群中的脑膜炎球菌感染或侵袭性脑膜炎球菌病（IMD）。Penmenvy将两种已获批准的疫苗的活性成分结合在一起，提供更好的保护，同时减少接种次数，简化了接种流程。 IMD是一种罕见但致命的感染，由脑膜炎奈瑟菌引起，可能导致脑膜炎（脑部肿胀）、败血症（血液感染），甚至在数小时内死亡。幸存者可能面临脑损伤、截肢、听力丧失和神经问题。16至23岁的青少年和年轻成年人风险更高。然而，只有不到13%的人完成了两剂疫苗接种，只有32%的人至少接种了一剂。 Penmenvy结合了Bexsero和Menveo疫苗的部分成分，通过一次注射保护免受五种最常见的脑膜炎奈瑟菌（A、B、C、W和Y）菌株的感染。此疫苗的简化接种方式可能会鼓励更多人进行免疫接种。 参考文献： 1.Wexler, M. FDA approves Alyftrek, once-daily triple-combination therapy for CF. Cystic Fibrosis. 02. 01. 2025. 2.Datroway (datopotamab deruxtecan) approved in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer. AZ Press Release. 17. 01. 2025. 3.Harrison, C. Vertex’s opioid-free drug for acute pain wins FDA approval. Nature Biotechnology. 2025. https://doi.org/10.1038/s41587-025-02590-3 4.Hartman, J. J., et al. Aficamten is a small-molecule cardiac myosin inhibitor designed to treat hypertrophic cardiomyopathy. Nat Cardiovasc Res 3, 1003–1016 (2024). https://doi.org/10.1038/s44161-024-00505-0 5.Press Release: Tolebrutinib designated Breakthrough Therapy by the FDA for non-relapsing secondary progressive multiple sclerosis. Sanofi Press Release. 13. 12. 2024. 6.Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria. Novartis Press Release. 31. 05. 2024. 7.Depemokimab accepted for review by the European Medicines Agency for use in asthma with type 2 inflammation and CRSwNP. GSK Press Release. 28. 01. 2025. 8.Das, J. FDA Approves 5-in-1 Vaccine Against Meningococcal Disease. WebMD. 9.McConaghie, A. et al. 2025’s Biggest New Launches. Scrip. 19. 02. 2025. 智药研习社近期直播预告 扫码领取CPHI & PMEC China 2025展会门票 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~