A Single-Dose, Bioequivalence and Food Effect Bioavailability Study in Healthy Volunteers Comparing the Commercial Lumacaftor 200 mg / Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) to the Lumacaftor 200 mg Film-Coated Tablet Formulation, and the Lumacaftor 200 mg Film-Coated Tablet Formulation in the Fasted to Fed State.

The objective of this study is to assess bioequivalence of lumacaftor from Lumacaftor 200 mg Film-Coated Tablet Formulation (Qanatpharma) versus the reference commercial product, Lumacaftor 200 mg /Ivacaftor 125 mg Combination Film-Coated Tablet (Orkambi®) in the fed state, and food-effect bioavailability of Lumacaftor 200 mg Film-Coated Tablet Formulation (Qanatpharma) in the fasted and fed state in healthy, non-smoking, male and non-pregnant female volunteers, 18 to 55 years of age, inclusive.

开始日期2023-11-17

申办/合作机构-

NCT04581408

/ Completed临床2期IIT

Mutation-specific Therapy for the Long QT Syndrome

Novel therapy for the Long QT Syndrome based on the mechanism of action of the disease-causing mutations
Long QT syndrome type 2 (LQT2) accounts for
35% of all LQTS cases and is difficult to manage, as beta-blockers frequently fail to provide full protection. Most LQT2 patients (pts) have a Class 2 mutation, which implies defective "trafficking".
Lumacaftor (LUM) is a drug developed and currently indicated for the treatment of cystic fibrosis (CF) in patients homozygous for the F508del mutation in the CFTR gene. LUM corrects protein folding and trafficking defects of mutant and misfolded CFTR channels, restoring their cell surface expression. The investigators recently demonstrated that LUM can rescue in vitro the LQTS phenotype observed in human induced pluripotent stem cell- derived cardiomyocytes (hiPSC-CMs) from pts with LQT2 Class 2 mutations (PMID: 29020304) and in these same two patients Orkambi administrated for 7 days at the same dosage approved for cystic fibrosis showed to reduce their QTc (PMID: 30753398).
With the present phase II clinical trial (MAST2) the investigators will enroll 20 LQT2 patients (see inclusion and exclusion criteria) and they will test in vivo the efficacy of Orkambi in shortening their QTc. Patients will be admitted to hospital for a maximum of 7 days (minimum in-hospital stay based on evidence of QTc shortening). Orkambi will be administered at the dose approved for cystic fibrosis and during the entire period continuous ECG monitoring through both telemetry and 12-lead 24-hr Holter monitoring will be performed and QTc length and morphology will be analyzed.

开始日期2021-06-15

申办/合作机构

Istituto Auxologico Italiano

NCT04415268

/ WithdrawnN/AIIT

Combined Effect of CFTR Protein Modulator Drugs and Exercise on Pulmonary Function, Fitness, Sweat Test and Quality of Life in Children With Cystic Fibrosis

This study aims to assess the effects of programmed exercise combined with CFTR protein modulator drugs in the cardiorespiratory fitness, strength, functional capacity and agility in a group of young patients with Cystic Fibrosis.

开始日期2020-06-09

申办/合作机构

Universidad Europea de Madrid SAU

100 项与芦马卡托相关的临床结果

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100 项与芦马卡托相关的转化医学

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100 项与芦马卡托相关的专利（医药）

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项与芦马卡托相关的文献（医药）

2025-06-23·DRUGS IN R&D

Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi^® (Lumacaftor/Ivacaftor) in Healthy Subjects.

Article

作者: Lidington, Darcy ; Papaelias, Alexandra ; Bolz, Steffen-Sebastian

BACKGROUND AND OBJECTIVE:

Lumacaftor is an active ingredient in the US Food and Drug Administration-approved combination medication Orkambi^®, which is used for treating cystic fibrosis. Experimental evidence suggests that lumacaftor can be used as a monotherapy to improve brain perfusion and memory in heart failure. To clinically assess this therapeutic intervention, a formulation with demonstrated bioequivalence to the currently approved combination product is required.

METHODS:

This comparative bioavailability and food-effect study compared lumacaftor pharmacokinetics in healthy patients following: (i) oral administration of lumacaftor (400 mg; Test Product) or Orkambi^® (lumacaftor 400 mg/ivacaftor 250 mg; Reference Product) in the fed state and (ii) oral administration of lumacaftor (400 mg; Test Product) in the fasted to fed state. Plasma lumacaftor concentrations were measured with a standard liquid chromatography with tandem mass spectrometry approach.

RESULTS:

The "Test-to-Reference ratio" of the geometric least-square means for maximum plasma concentration and area under the curve met the Food and Drug Administration-defined criteria for bioequivalence; median times to maximum plasma concentration values were not statistically different. The "Fed to Fasted ratio" of the geometric least-square means for maximum plasma concentration and area under the curve indicated a clear food effect on bioavailability. Lumacaftor exposure was approximately two times higher when administered with fatty foods than when taken in a fasting state. The monosubstance formulation was well tolerated.

CONCLUSIONS:

We conclude that the lumacaftor monosubstance formulation delivers lumacaftor exposure that is not meaningfully different than the currently approved combination product.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT05968612.

2025-06-01·AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Lumacaftor inhibits channel activity of rescued F508del cystic fibrosis transmembrane conductance regulator

Article

作者: Rowe, Steven M. ; Thompson, Jake ; Hagedorn, Zachary J. ; Rodriguez-Cruz, Kevin ; Wen, Hui ; Bono, Taylor R. ; McNicholas, Carmel M. ; Phillips, Aubrey J. ; Freeman, Alana J. ; Ali, Judge ; Fu, Lianwu ; Ambrosetti, Adam D. ; Palacio, Hayes ; Wang, X. Robert ; Gilliland, Stephanie D. ; Nguyen, Rodney

Small-molecule correctors bind to F508del cystic fibrosis transmembrane conductance regulator (CFTR) and restore its trafficking to the plasma membrane to function as an anion channel. Despite its high efficacy as a corrector, lumacaftor inhibits the channel opening of rescued F508del CFTR, making it a weak CFTR modulator. The current work highlights the impact of CFTR correctors on the channel activity of rescued F508del CFTR as an important variable in the efficacy of modulator therapy.

2025-06-01·EUROPEAN RESPIRATORY JOURNAL

Relationship between theratyping in nasal epithelial cells and clinical outcomes in people with cystic fibrosis

Article

作者: Shaw, Michelle ; Eckford, Paul D W ; Bear, Christine ; Avolio, Julie ; Gonska, Tanja ; Ratjen, Felix ; Moraes, Theo J ; Gunawardena, Tarini ; Stanojevic, Sanja ; Ouyang, Hong ; Bartlett, Claire

Background:

In people with cystic fibrosis (pwCF), human nasal epithelial cell (HNEC) cultures can be used to assess response to CF transmembrane conductance regulator (CFTR) modulators. However, thresholds of in vitro responses that predict clinical benefit remain poorly understood. In this study we describe the concordance between in vitro response in HNECs and clinical outcomes in pwCF harbouring the F508del variant, treated with either lumacaftor/ivacaftor, tezacaftor/ivacaftor or elexacaftor/tezacaftor/ivacaftor.

Methods:

Response of HNECs to CFTR modulators was assessed by CFTR-mediated chloride current stimulated by forskolin or inhibited by CFTRinh-172 in both pwCF and healthy controls. Clinical response was defined as change in forced expiratory volume in 1 s (FEV1), lung clearance index (LCI), sweat chloride or respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) between baseline and within 3 months after the start of modulator treatment.

Results:

In 58 unique in vitro–clinical pairs, in vitro measures of functional rescue correlated with changes in FEV1, LCI and sweat chloride, but not CFQ-R. The concordance between in vitro response and clinical outcomes was highest when a composite outcome was used. For example, an in vitro response of 10% of healthy controls had positive and negative predictive values of 90.5% and 100%, respectively, for a clinical response in either FEV1, LCI or sweat chloride.

Conclusions:

We identified thresholds of nasal epithelial cell theratype response in pwCF to predict clinical benefit from CFTR modulator therapy. The utility of this therapy testing platform to predict a clinical response improves when multiple clinical outcome measures are combined.

项与芦马卡托相关的新闻（医药）

2025-07-01

·医药观澜

这种“难缠”的肺部疾病夺走了数万人的生活，创新疗法为他们带来“新生”

▎药明康德编者按：囊性纤维化（CF）是一种遗传性疾病，会对患者的肺部、消化系统和身体其他器官造成严重损害，全球约有10万患者深受其害。近年来多款变革性靶向疗法获批上市，深刻改变了CF的治疗现状，为许多患者带来了“新生”。当下，还有超40个创新项目管线进入临床研究，有望为更多患者带来新的希望。作为全球医药创新的赋能者，药明康德长期以来也在为包括囊性纤维化在内的各类疾病疗法开发提供一体化、端到端的CRDMO服务，助力全球合作伙伴加速新药问世。今年4月，素有“诺贝尔奖风向标”之称的加拿大盖尔德纳国际奖授予两位在囊性纤维化研究领域作出突破性贡献的科学家。Michael J. Welsh博士与Paul Negulescu博士凭借其在该遗传疾病分子机制研究及创新药物开发方面的开创性工作获此殊荣。其中，Welsh博士及其研究团队通过系统性研究，首次证实CFTR蛋白的氯离子通道功能，这一发现革新了科学界对囊性纤维化发病机制的认识，为开发靶向治疗奠定了基础。Negulescu博士领导的Vertex Pharmaceuticals研发团队突破技术瓶颈，研发出首个CFTR蛋白折叠校正剂，开创了囊性纤维化靶向治疗的新纪元。囊性纤维化（CF）是一种罕见遗传病，患者肺部最常受到影响，产生的黏液浓稠且黏滞，会堵塞肺部输送空气的管道，引起慢性肺部感染和进行性肺损伤，甚至影响胰腺、肝脏、肾脏等，最终可能导致死亡。该疾病是由于囊性纤维化跨膜传导调节因子（CFTR）基因发生突变、导致CFTR蛋白缺失或功能缺陷引起。图片来源：123RF在“特效药物”面世之前，CF患者不得不日常面对身体上的长期不适，可能每天都要服用抗生素、治疗并发症的酶类药物，以及常备排痰、雾化、呼吸治疗、输液的医疗器械等。所幸，近年来针对性治疗囊性纤维化的CFTR蛋白调节剂疗法获美国FDA批准上市，为许多囊性纤维化患者带来“新生”。这类药物可以改善CFTR基因变异产生的缺陷蛋白的功能，使患者不再依赖其他耗时的治疗方法，并同时摆脱了呼吸道感染的威胁，得以自由呼吸。目前，FDA已经批准多种 CFTR 调节剂或其治疗组合上市，例如艾伐卡托（ivacaftor）、艾伐卡托/芦马卡托（lumacaftor）、艾伐卡托/ tezacaftor，以及三联组合Trikafta（艾伐卡托/tezacaftor/ elexacaftor），这些药物可作用于CFTR蛋白的不同部分，共同产生协同效应。尤其是于2019年获FDA批准上市的Trikafta，该产品成分中的elexacaftor是新一代CFTR蛋白矫正剂，可恢复携带F508del突变的CFTR蛋白的功能。因此Trikafta适用于CFTR基因上至少出现一个F508del基因突变（约90%的患者携带该突变），包括F508del-CFTR最小功能突变（该突变会导致CFTR蛋白极少甚至没有）的患者。因此，这款新药具有治疗90%囊性纤维化患者的潜力。该药物还被行业媒体Evaluate Pharma列为了2024年十大重磅药物之一。2024年底，又一则好消息传来：FDA批准Vertex公司开发的另一款CFTR调节剂组合疗法Alyftrek（vanzacaftor/tezacaftor/deutivacaftor）上市，用于治疗6岁及以上、携带至少一个F508del突变或其他对Alyftrek有反应的CFTR基因突变的囊性纤维化患者，进一步拓展了适用的患者人群。这款三联疗法也被Evaluate Pharma列为潜在重磅疗法之一。这些CFTR调节剂疗法的到来，改善了多数CF患者的生活。尽管如此，但临床上仍然存在未被满足的治疗需求。比如目前的治疗方法不能预防疾病的持续进展；再比如，某些突变患者仍无法从中获益——一些突变导致功能性CFTR蛋白无法产生，使得现有治疗无效。因此，业界正在努力开发新的囊性纤维化治疗药物。通过公开渠道梳理，全球范围内还有超过40个在研疗法处于积极的临床研究阶段，主要包括小分子、mRNA疗法，以及少数寡核苷酸疗法和基因疗法，它们有望在将来为缺乏治疗方案的囊性纤维化患者带来更多治疗选择。解决递送挑战，核酸药物治疗有望突破在现有囊性纤维化临床管线中，核酸类药物备受关注。近年来随着递送技术的突破，核酸类药物在疾病治疗领域大放异彩。目前，多款以CFTR为靶点的mRNA疗法处于囊性纤维化1期或2期临床研究中。比如Vertex Pharmaceuticals与Moderna合作研发的一款mRNA疗法VX-522，试图恢复肺部CFTR蛋白功能，为无法从CFTR调节剂中获益的患者提供治疗选择。具体而言，VX-522把全长CFTR mRNA封装在脂质纳米颗粒（LNP）中，通过吸入的方式输送到肺部。一旦递送到气道中的靶细胞，mRNA就能够产生功能性的CFTR蛋白。该产品目前正处于1/2期临床阶段，还被行业媒体评为“2025上半年值得关注的十大临床试验”。在这一领域，还有一些分子管线取得进展，例如Arcturus Therapeutics的候选mRNA药物ARCT-032于2023年底获FDA授予的孤儿药资格，用于治疗囊性纤维化；ReCode Therapeutics在研的RCT2100于今年3月也获得FDA授予治疗囊性纤维化的孤儿药资格。此外，还有若干反义寡核苷酸（ASO）疗法也在临床阶段探索治疗囊性纤维化的潜力。例如SpliSense公司在研的ASO疗法SPL84，拟开发治疗CFTR基因中携带某剪接突变的患者。Ionis Pharmaceuticals在研的ION-827359——一款旨在降低上皮钠通道（ENaC）蛋白的ASO疗法。研究表明，ENaC的过度活跃与钠吸收增加是囊性纤维化的特征之一。值得一提的是，上述拟开发治疗囊性纤维化的mRNA疗法中，多款使用了脂质纳米颗粒（LNP）递送技术。这是由于，靶向CFTR的核酸类药物只有递送到肺部，才能在肺部发挥治疗作用。而mRNA具有负电荷以及生物大分子属性，不能直接作用于细胞或进行注射，因此需要安全高效的递送系统来共同提升治疗效果。在众多mRNA递送系统中，LNP是使用率较高、且备受关注的递送系统。近年来的研究发现，通过调整构成LNP的脂质分子的类型和比例，能够诱导LNP被肝脏以外的器官或组织吸收。在这一领域，药明康德作为全球医药创新的赋能者，多年来持续建立相关技术和能力，以更好地满足合作伙伴的mRNA类药物研发需求。公开资料显示，药明康德DMPK不仅建立了针对mRNA药物递送系统的常规LC-MS/MS分析方法，能够快速完成递送系统化合物的分析并解决遇到的问题；还建立了一套完整的测定5'帽加帽率的高分辨色谱分析方法，能够系统评估mRNA药物的加帽率；另外针对mRNA药物的分析，建立了高通量、智能化分析平台，包含QIAcube HT 高通量核酸提取仪、KingFisher全自动核酸提取仪、QIAgility自动化PCR体系构建、QuantStudio™ 7 Flex，能够快速完成大批量的样品分析，缩短项目分析周期。同时，药明康德DMPK专业的核酸分析团队能够从专业的角度完成客户的问题、引物设计、项目方法开发等，旨在最大程度满足客户的项目分析需求，加速新药研发。新机制涌现，更多管线展现潜力在CF临床管线中，创新小分子占多数。其中，大多数管线的靶点仍然聚焦CFTR，但也涌现出一些新的作用机制。比如，cystetic Medicines利用两性霉素B（amphotericin B）——一种能在细胞中独立形成离子通道的天然小分子，使其作为一个分子假体（molecular prosthetic），从而替代CFTR蛋白行使CFTR的离子通道功能，以期为目前无法从CFTR调节剂中获益的囊性纤维化患者带来新疗法。这种新型治疗方式此前被《自然》杂志报道。再如，Sionna Therapeutics正在开发使CFTR功能正常化的小分子新药组合，其方法是通过直接稳定CFTR的核苷酸结合结构域1（NBD1），使CFTR功能尽可能恢复到接近正常。目前，该公司正在开发多个小分子或组合疗法，通过改善或纠正CFTR功能来治疗囊性纤维化。在CF临床管线中，还有基因疗法方向的探索。比如Spirovant Sciences公司正在开发的AAV增强平台旨在将CFTR基因的全功能拷贝引入呼吸系统的靶细胞，以解决囊性纤维化的根本原因。囊性纤维化是纤维化类疾病类型之一。作为创新的赋能者，药明康德长期以来也在为此类疾病创新疗法的开发提供各种服务，通过一体化、端到端的CRDMO业务模式，从早期药物发现和研究（R）、开发（D）到生产（M）都能为合作伙伴提供支持，助力更多突破性疗法造福病患。根据公开信息，在过去3年中，药明康德纤维化药物开发一体化平台助力全球合作伙伴向美国FDA/中国NMPA提交了超过40个纤维化药物相关的IND申请；药明康德测试业务平台的药性评价部也能为包括CFTR蛋白调节剂在内的各类药物的体内、体外药物代谢与药代动力学（DMPK）研究提供支持。在这个科学创新不断涌现的时代，希望产业创新生态圈继续携手，将新药理念变为现实，加速创新疗法问世，让更多患者能够享受更美好的生命。参考资料：[1] Sionna Therapeutics Announces Presentation of Preclinical Data that Demonstrate Proprietary Dual Combination Therapies Enable Full CFTR Correction in CFHBE Model. Retrieved June 06, 2025. From https://www.globenewswire.com/news-release/2025/06/06/3095237/0/en/Sionna-Therapeutics-Announces-Presentation-of-Preclinical-Data-that-Demonstrate-Proprietary-Dual-Combination-Therapies-Enable-Full-CFTR-Correction-in-CFHBE-Model.html[2] cystetic Medicines官网. From https://cysteticmedicines.com/[3]ReCode Therapeutics Receives U.S. FDA Orphan Drug Designation for RCT2100 for the Treatment of Cystic Fibrosis.Retrieved March 25, 2025. From https://recodetx.com/recode-therapeutics-receives-u-s-fda-orphan-drug-designation-for-rct2100-for-the-treatment-of-cystic-fibrosis/[4]Kumar, S., Tana, A., & Shankar, A. (2014). Cystic fibrosis—What are the prospects for a cure?. European journal of internal medicine, 25(9), 803-807.版权说明：本文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。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：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。

上市批准临床研究

2025-06-23

·医药观澜

从"致命诅咒"到医学奇迹：创新疗法已获批上市，纪念囊性纤维化的百年抗争

编者按：当前，罕见病药物研发仍面临诸多挑战，需要整个生物医药生态圈协同创新。作为行业创新的重要推动者，药明康德凭借其一体化、端到端的CRDMO平台，通过技术创新、高效协同和全流程服务，持续为合作伙伴的罕见病新药研发提供关键支持。在这一过程中，药明康德也见证了全球医药行业为罕见病患者带来突破性疗法的持续努力。本文将聚焦囊性纤维化治疗领域的代表性突破，展现医药界为攻克这一罕见病所付出的不懈探索.图片来源：123RF一个17岁少年与疾病的抗争“有段时间，我的日子糟透了。”17岁的新西兰少年在在一次访谈中坦诚道。作为校篮球队队长，他本该享受青春最灿烂的时光，但命运给了他一个残酷的考验——囊性纤维化。这种特殊的罕见疾病像无形的枷锁，逐渐侵蚀着他的肺部、胰腺等功能。金黄色葡萄球菌在体液中滋生，胰腺炎发作时，剧痛甚至让他只能蜷缩在床上，只能靠止痛药勉强支撑。“曾有一段时间，我几乎认为自己再也没有机会站在球场上，做那个热爱篮球、充满梦想的自己了。”他回忆道。2019年，医学的曙光降临——Trikafta(elexacaftor/tezacaftor/ivacaftor)三联疗法的问世，让这位少年的命运发生了翻天覆地的变化：卧床不起的日子一去不复返，曾被病魔禁锢的他也重新回到了心爱的球场上。少年的故事见证了医学领域的又一奇迹，从囊性纤维化基因的发现，到CFTR调节剂的研发突破，这是众多基础研究、医药研发者的共同努力最终凝结成的救命的硕果。全球目前约有10万人正遭受着囊性纤维化的困扰。而该疗法有望治疗全球约九成的囊性纤维化患者，帮助他们降低疾病严重程度，减少粘液造成的各类器官损伤，并显著改善肺部功能。破解"致命诅咒"：囊性纤维化的百年探索18世纪，在欧洲流传着一个可怕的传说：若刚出生婴儿额头带有特殊咸味，便难逃早夭的命运。这个被称为"咸味诅咒"的现象，实则是人类最早对囊性纤维化的模糊认知。直到1938年，美国病理学家Dorothy Andersen博士才首次科学描述了这种疾病，他发现患者胰管呈现囊状并伴随广泛的纤维化现象。诊断技术的突破发生在1948年纽约的一个酷暑。Paul di Sant’Agnese医生注意到，中暑患儿中囊性纤维化患者的汗液盐分异常偏高。这一发现不仅解开了"咸味诅咒"之谜，更催生了经过不断改进并沿用至今的汗液检测法，极大改善了诊断体验。真正的治疗突破始于对疾病机制的深入探索。上世纪80年代，加州大学圣地亚哥分校的Paul Quinton教授发现患者汗腺细胞的氯离子通道存在异常。随后，徐立之教授和Francis Collins教授合作锁定了致病基因——CFTR基因以及引发囊性纤维化最常见的突变F508del。这些关键发现为靶向药物研发指明了方向，最终催生了2019年改变“游戏规则”的Trikafta三联疗法。图片来源：123RF为“沉船”上的患者打造“救生艇”"我感觉自己就像在一艘正在沉没的船上，而其他救生艇都已离开。"一位囊性纤维化患者的这番话，深深刺痛了Fredrick Van Goor博士的心。作为Vertex Pharmaceuticals囊性纤维化研究项目的负责人，他研发囊性纤维化疗法二十多年，并参与了数百次与患者的交谈。而患者的这句话令他记忆犹新，成为他十多年如一日坚持研发突破性疗法，为患者打造全新“救生艇”的精神动力。21世纪初，囊性纤维化的治疗仍停留在“治标”层面：物理治疗清除粘液、抗生素控制感染。面对CFTR基因突变导致的根本性问题，彼时业界还束手无策。2001年，Vertex公司收购了Aurora Biosciences——该公司与囊性纤维化基金会正在合作寻找可能改善缺陷CFTR基因产生的异常蛋白功能的化合物。之后，Vertex公司接手继续推进囊性纤维化的研究，Fredrick博士也接受了这个被许多人视为“不可能完成的任务”——通过一种分子来逆转特定突变对蛋白的影响，这在当时还是一个巨大的难题。但他带领团队迎难而上。他们首先系统分析了CFTR突变的类型：有些阻止蛋白合成，有些妨碍蛋白转运至细胞膜，还有些使膜上的蛋白功能失常。这些突变都会破坏氯离子转运过程，造成盐分吸收异常。最为常见的F508del突变（约90%的患者携带该突变）更是"双重打击"——既阻碍蛋白转运又影响蛋白发挥功能。面对这种复杂性，研究团队意识到：需要设计研发组合药物，最好能同时解决转运和功能两个问题：一种发挥校正剂作用，引导突变蛋白前往细胞膜，另一种帮助蛋白到达位置后稳定发挥作用。研究团队采取了“分步突破”的策略。2012年，靶向药物ivacaftor(Kalydeco)获批，用于治疗携带至少一个G551D突变的囊性纤维化患者。它能修复G551D突变导致的通道开放缺陷。虽然G551D突变患者占比不高，但这一突破证明了治疗囊性纤维化不再是幻想。随后，团队转向更普遍的F508del突变。他们开发了校正剂lumacaftor——它可以作为有效的校正剂引导突变蛋白前往细胞膜，与ivacaftor联用形成Orkambi疗法，既能让CFTR蛋白前往细胞膜，也能稳定打开并发挥跨膜通道的功能，这就很好地解决了F508del突变患者会面临的两大问题。在后续研究中，Fredrick团队继续优化改进：用tezacaftor替换lumacaftor，并加入第二种校正剂elexacaftor。最终，革命性的三联疗法Trikafta在2019年问世。两种校正剂作用于CFTR蛋白的不同部分，共同产生协同效应。这种组合在改善F508del突变CFTR功能方面非常有效，可以惠及仅携带一个F508del突变的患者。时任Vertex公司首席执行官的Jeffrey Leiden博士在采访中表示，这是一款具有治疗90%囊性纤维化患者潜力的突破性疗法。从古老的传说到现代靶向治疗，人类对囊性纤维化认知的每一次突破都凝聚着科研人员的智慧与坚持。Trikafta的成功是囊性纤维化治疗的重大突破和里程碑，也映射出全球科学家、医药产业界对攻克疾病的坚定决心。破局“罕治”困境：创新生态助力罕见病药物研发囊性纤维化是众多罕见病类型之一，其治疗突破也是罕见病药物研发中令人鼓舞的范例之一。根据世界卫生组织统计，全球约有6000多种罕见病，患者总数超3亿人。然而令人遗憾的现实是，目前仅不到5%的罕见病拥有有效的治疗方法。新药研发向来充满挑战：平均需要26亿美元投入和十余年时间，且超过90%的候选药物会在临床试验阶段失败。这种"高投入、高风险、低成功率"的困境在罕见病领域尤为突出——患者群体规模有限，使得研发成本更高、周期更长。破解这一难题，需要全球生物医药生态圈的协同合作和共同努力。作为创新的赋能者、客户信赖的合作伙伴以及全球健康产业的贡献者，药明康德多年来也通过其独特的CRDMO业务模式，持续助力全球合作伙伴加速开发罕见病创新药开发。面对创新药研发的多种挑战，药明康德一体化、端到端的CRDMO模式有助于为合作伙伴大幅缩短新药研发时间，降低研发成本，让包括罕见病在内的各类疾病药物研发更高效、更易行。在全球各界的共同努力下，我们期待更多创新疗法问世，让罕见病不再"罕治"，为患者带来新希望。参考资料：[1] A Trikafta Success Story. Retrieved April 28, 2025 from https://www.cfnz.org.nz/news-and-events/latest-news/a-trikafta-success-story/[2] Life-Changing Cystic Fibrosis Treatment Wins $3-Million Breakthrough Prize. Retrieved April 28, 2025 from https://www.scientificamerican.com/article/life-changing-cystic-fibrosis-treatment-wins-3-million-breakthrough-prize/[3] Cystic fibrosis drugs target the malformed proteins at the root of the disease. Retrieved April 28, 2025 from https://www.nature.com/articles/d41586-020-02106-w[4] Cystic Fibrosis: Sam's Story. Retrieved April 28, 2025 from https://www.hopkinsmedicine.org/health/conditions-and-diseases/cystic-fibrosis/patient-story-sam[5] Ratjen, F., Bell, S., Rowe, S. et al. Cystic fibrosis. Nat Rev Dis Primers 1, 15010 (2015). https://doi.org/10.1038/nrdp.2015.10版权说明：本文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。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：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。

上市批准突破性疗法

2024-12-19

·PRNewswire

A Success Story: Digital Opinion Leader Analysis for Cystic Fibrosis Treatments | DelveInsight

A case study on how a pharmaceutical company specializing in cystic fibrosis treatments turned to DelveInsight for comprehensive analysis and insights into the digital cystic fibrosis landscape in the UK. DelveInsight identified key Digital Opinion Leaders (DOLs) and synthesized their opinions, enabling the client to strategically leverage these insights for drug development, marketing, and patient advocacy, ensuring a competitive edge in the cystic fibrosis market. LAS VEGAS, Dec. 19, 2024 /PRNewswire/ -- DelveInsight, a leader in healthcare competitive intelligence and consulting company, published a success study on Digital Opinion Leader (DOL) Analysis in the Cystic Fibrosis Market . A pharmaceutical company specializing in cystic fibrosis treatments approached DelveInsight to conduct an in-depth analysis of DOLs in the UK. The client sought to identify key digital influencers and understand their perspectives on cystic fibrosis treatments, leveraging these insights to inform drug development, marketing strategies, and patient advocacy efforts. Cystic fibrosis is a life-limiting autosomal recessive genetic disorder that primarily affects the lungs and digestive system, caused by mutations in the CFTR gene. According to DelveInsight's latest Cystic Fibrosis Market and Epidem Forecast Report, the estimated total diagnosed prevalent cases of cystic fibrosis in the 7MM in 2023 were ~68K cases. The UK had the highest number of diagnosed cystic fibrosis cases, with nearly 11K, followed by France with 7.5K and Germany with 7K. In the EU4 and the UK, the cystic fibrosis market size was nearly USD 7 billion, accounting for almost 39.4% of the total 7MM market size in 2023. This is expected to increase significantly by 2034. Download the Sample Report to Explore Future Trends in the Cystic Fibrosis Market In the field of cystic fibrosis, DOLs play a significant role in shaping perceptions and influencing the direction of treatment, policy, and patient care. These are influential healthcare professionals or researchers who have an active online presence and contribute to discussions, research, and advocacy. For pharmaceutical companies developing cystic fibrosis treatments, understanding the DOL landscape is crucial for gaining insights into market dynamics and stakeholder perceptions and identifying strategic opportunities for drug development, marketing, and patient advocacy. Several medications have been approved to manage cystic fibrosis, with therapies targeting the CFTR protein to correct its defects. One of the most groundbreaking treatments is TRIKAFTA, a combination of elexacaftor, tezacaftor, and ivacaftor, which has revolutionized cystic fibrosis treatment by improving lung function in patients with specific genetic mutations. Other notable drugs include SYMDEKO (tezacaftor/ivacaftor) and ORKAMBI (lumacaftor/ivacaftor), which also target the CFTR protein. These therapies aim to address the root cause of the disease, improving symptoms and quality of life for patients. However, despite these advancements, the current treatment landscape still faces challenges, such as variability in treatment efficacy and accessibility to newer therapies for certain patient populations. The pipeline for cystic fibrosis treatments continues to evolve, with several promising drugs in the cystic fibrosis pipeline. Ensifentrine (Verona Pharmaceuticals) is a dual inhibitor of the enzymes responsible for inflammation and mucus production in the lungs, showing potential as an add-on therapy for patients with CF. VX-121/TEZ/VX-561 (Vertex Pharmaceuticals) is another exciting treatment, combining triple therapy to enhance CFTR function and improve lung function. LAU-7b (Laurent Pharmaceuticals Inc.) aims to restore CFTR function and reduce inflammation. Lonodelestat (Pari Pharma GmbH) is being investigated for its ability to reduce neutrophil elastase and inflammation in the lungs of CF patients. These drugs, if successful, could significantly improve treatment options and outcomes for CF patients. Several companies are at the forefront of developing treatments for cystic fibrosis. Eloxx Pharmaceuticals, Inc. focuses on treatments that aim to restore protein function in CF patients with specific genetic mutations. Vertex Pharmaceuticals is a leader in the CF market, with therapies like TRIKAFTA and ongoing pipeline developments. Santhera Pharmaceuticals is exploring potential treatments to address pulmonary issues in CF patients. DelveInsight helped the client by curating insights from the digital cystic fibrosis landscape and analyzing the opinions of key digital influencers. By identifying and analyzing these DOLs, DelveInsight provided actionable insights and strategic recommendations for the client. The company gained a deeper understanding of the market dynamics, stakeholder perceptions, and the evolving digital landscape surrounding cystic fibrosis. These insights were invaluable for informing drug development strategies, understanding the gaps, patient burden,, and patient advocacy initiatives. Armed with comprehensive information on DOLs and their impact, the client was better equipped to make informed decisions, enhance patient engagement, and improve the overall market approach for cystic fibrosis treatments. Our client approached us with multiple objectives: Understand the DOL Landscape in the UK for cystic fibrosis. Identify Key Digital Opinion Leaders influencing discussions about cystic fibrosis. Analyze the Opinions of DOLs on treatment options and emerging therapies. Leverage Insights to refine drug development, marketing strategies, and patient advocacy efforts. Outcome of DelveInsight's Digital Opinion Leader Analysis: We identified and profiled key digital opinion leaders (DOLs) in the UK cystic fibrosis community, focusing on those with strong online presence, high engagement, and CF expertise. Through content analysis, we gained insights into opinions, trends, and key areas like treatment, patient care, advocacy, and research within the CF community. We mapped the CF digital ecosystem, highlighting connections and interactions between DOLs and stakeholders revealing network dynamics and engagement patterns. We assessed the impact of DOLs using metrics like follower count, engagement rate, and content virality, helping clients prioritize engagement strategies and collaborations. DelveInsight specializes in comprehensive Key Opinion Leader (KOL) and Digital Opinion Leader (DOL) opinion analysis, offering deep insights into industry trends, expert perspectives, and influencer dynamics. Our expertise enables clients to identify and understand the nerve of the trends by providing analysis through the most impactful thought leaders and digital influencers. By leveraging our tailored strategies and data-driven approaches, we help businesses strengthen their approach, refine decision-making, and amplify their market impact. Connect with us today to explore how we can support your specific needs and discuss opportunities for strategic engagement. Request a Proposal Now ! Why Choose DelveInsight? DelveInsight offers comprehensive expertise in the respiratory disease domain, providing in-depth market research, consulting services, and pipeline analysis tailored to the evolving needs of the industry. With a sharp focus on respiratory conditions, DelveInsight delivers robust reports covering emerging therapies, market trends, competitive landscapes, and unmet needs. DelveInsight's respiratory-specific solutions empower stakeholders to make data-driven decisions, optimize their R&D efforts, and seize growth opportunities in the dynamic and rapidly advancing respiratory disease market. Market Assessment Services in the Genetic Disorders Segment, DelveInsight, provide a 360-degree view of the market landscape. Our expertise includes epidemiology-based market forecasts up to 2034, offering precise insights into current and future market share uptake of emerging therapies. These forecasts, combined with detailed analyses of emerging trends, competitive dynamics of the pipeline therapies, and unmet needs, enable stakeholders to strategize effectively and identify growth opportunities. Whether it's the pipeline analysis, pricing strategies, or competitive benchmarking, DelveInsight delivers actionable intelligence tailored to your goals. Contact us Today to discuss how our services can drive success in your endeavors within the genetic disorder market. Competitive Intelligence Services Tailored to Genetic Disorder Domain: DelveInsight's competitive intelligence services provide real-time, accurate insights across the different therapeutic domains and genetic disorders being one of our fortes, providing detailed insights into advancements across rare and inherited conditions such as cystic fibrosis, Duchenne muscular dystrophy, and sickle cell anemia etc to name a few. Our services analyze competitors' pipelines, clinical trial progress, gene and cell therapy innovations, and market entry strategies, as well as regulatory updates and patent landscapes specific to genetic disorders. This intelligence enables stakeholders to identify emerging threats, uncover growth opportunities, and develop targeted strategies to remain competitive in this evolving therapeutic area. Connect with us today to explore how we can help you succeed in the genetic disorders market. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform , PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准

100 项与芦马卡托相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10134	芦马卡托	R07AX30	DB09280

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
囊性纤维化	临床3期	捷克	Vertex Pharmaceuticals, Inc.	2013-05-01
囊性纤维化	临床3期	爱尔兰	Vertex Pharmaceuticals, Inc.	2013-05-01
囊性纤维化	临床3期	意大利	Vertex Pharmaceuticals, Inc.	2013-05-01
肝损伤	临床1期	捷克	Vertex Pharmaceuticals, Inc.	2013-06-01
肝损伤	临床1期	斯洛伐克	Vertex Pharmaceuticals, Inc.	2013-06-01
斯塔加特病	临床前	美国	Johns Hopkins University School of Advanced International	2018-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ESGCT2023	N/A	囊性纤维化	-	VX809 (Normal Human Bronchial Epithelial (NHBE) cells)	窪遞淵憲襯鑰鑰鏇網觸(積醖鏇鏇壓範簾襯醖遞) = approximately 2 to 2.5 times 獵顧鏇鑰鹽糧壓醖餘壓 (鹹艱衊築衊簾鬱選廠選 )	-	2023-10-24
				VX809 (Cystic Fibrosis Bronchial Epithelial (CFBE) cells)
NCT03601637 (CTgov)	临床3期	囊性纤维化	61	IVA+LUM (Part B: LUM/IVA)	鏇鏇獵簾壓顧鬱顧觸襯 = 壓觸壓憲選鑰膚餘膚廠憲蓋壓鏇鬱鹽淵選製構 (積鏇夢醖製築構範構鹽, 鏇鬱鏇構繭壓築膚範願 ~ 遞糧遞觸鑰衊積淵壓鹹) 更多	-	2023-01-06
				IVA+LUM (Part A: LUM/IVA)	鑰鬱艱鹽醖艱糧鑰鏇糧 = 鹹窪淵襯構鑰繭餘獵積觸膚構鹽願夢鏇遞鏇製 (窪衊醖製願憲艱糧製顧, 窪廠範選鹽繭築獵製膚 ~ 鏇鑰顧衊憲觸網壓廠鬱) 更多
NCT02514473 (CTgov)	临床3期	囊性纤维化	206	Placebo (Placebo)	獵鏇衊觸鹽夢餘構鹽積(選廠襯網築廠廠蓋選艱) = 鹽夢鏇構遞顧艱淵廠廠網蓋構壓夢餘獵築窪鹽 (壓網鏇願鬱鹹壓鬱觸壓, 0.13) 更多	-	2017-10-23
				VX-770+VX-809 (LUM/IVA)	獵鏇衊觸鹽夢餘構鹽積(選廠襯網築廠廠蓋選艱) = 觸製廠簾襯餘壓顧遞鹹網蓋構壓夢餘獵築窪鹽 (壓網鏇願鬱鹹壓鬱觸壓, 0.13) 更多
NCT02514473 (Pubmed \| Lancet Respir Med) 人工标引	临床3期	囊性纤维化 F508del	204	lumacaftor+ ivacaftor	鹽糧窪鹽構鹽積壓鑰廠(醖齋齋製鹽夢獵範積選): difference = -1.09 (95% CI, -1.43 ~ -0.75), P-Value = <0.0001 更多	积极	2017-07-01
				Placebo
NCT01897233 (Pubmed \| Pediatrics \| Am J Respir Crit Care Med) 人工标引	临床3期	囊性纤维化 F508del mutation	58	Lumacaftor/Ivacaftor	憲窪遞繭鹹壓鹹餘淵網(鹹鬱觸獵築淵鹹顧醖獵) = 願構壓鹽製範簾觸鹹壓積選鑰獵夢顧鏇襯網艱 (膚繭膚襯餘選選窪築製 ) 更多	积极	2017-04-01
NCT01225211 (Pubmed)	临床2期	囊性纤维化	126	Lumacaftor/Ivacaftor	顧鹽製範蓋淵鏇憲蓋繭(糧餘鑰蓋廠鏇鹹淵範糧) = 願選築壓淵鏇醖襯餘廠鏇範範顧繭選積願憲膚 (憲構廠壓簾製膚齋顧鏇 ) 更多	-	2017-02-01
				Placebo	顧鹽製範蓋淵鏇憲蓋繭(糧餘鑰蓋廠鏇鹹淵範糧) = 顧襯鏇築網鑰繭鑰鹹範鏇範範顧繭選積願憲膚 (憲構廠壓簾製膚齋顧鏇 ) 更多
NCT00865904 (CTgov)	临床2期	囊性纤维化	93	Placebo (Placebo)	襯廠蓋構壓糧網積鏇壓 = 壓鑰餘糧繭鬱窪鹽獵夢糧顧糧廠鏇積夢願鹹齋 (範醖鹹構繭餘鑰夢衊蓋, 鹽壓膚製醖艱窪壓積蓋 ~ 憲膚窪構獵餘簾網齋廠) 更多	-	2015-08-28
				VX-809 (VX-809, 25 mg)	襯廠蓋構壓糧網積鏇壓 = 鹽窪醖艱顧糧淵鹹窪夢糧顧糧廠鏇積夢願鹹齋 (範醖鹹構繭餘鑰夢衊蓋, 窪廠鏇夢艱廠壓簾製衊 ~ 憲艱淵鑰顧齋艱壓獵淵) 更多
NCT01225211 (Pubmed \| Lancet Respir Med)	临床2期	囊性纤维化	312	Lumacaftor 200 mg + Ivacaftor 150 mg	鹹廠構願蓋網壓鬱艱鏇(淵鹽觸製齋鹹鹹夢築餘) = 艱醖廠製觸膚憲齋網遞廠築鑰鏇鹹構艱窪觸醖 (憲選獵膚衊壓壓構獵鹹 )	-	2014-07-01