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

NCT04235140 / Completed临床3期

A Phase 3, Open-label, and Rollover Study to Evaluate the Long-term Safety and Tolerability of Lumacaftor/Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation

This is a Phase 3, multicenter, open-label and roll-over study in participants who are 12 to <24 months of age at initiation of Lumacaftor/Ivacaftor (LUM/IVA) treatment.

开始日期2020-02-24

申办/合作机构

Vertex Pharmaceuticals, Inc.

NCT03894657 / CompletedN/AIIT

Validation of Respiratory Epithelial Functional Assessment to Predict Clinical Efficacy of Orkambi®. Pathway to Personalized Therapy in Cystic Fibrosis

The purpose of the study is to investigate whether the correction of CFTR function by Lumacaftor/Ivacaftor in a patient-derived primary nasal cell model is a surrogate biomarker for respiratory improvement in Orkambi® treated patients.

开始日期2019-12-18

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

100 项与依伐卡托/芦马卡托相关的临床结果

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100 项与依伐卡托/芦马卡托相关的专利（医药）

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113

项与依伐卡托/芦马卡托相关的文献（医药）

2024-11-01·JOURNAL OF PHYSIOLOGY-LONDON

Restoring CFTR function with Orkambi decreases the severity of alcohol‐induced acute pancreatitis

Article

作者: Hegyi, Péter ; Ébert, Attila ; Gál, Eleonóra ; Galla, Zsolt ; Venglovecz, Viktória ; Tóth, Emese ; Maléth, József ; Monostori, Péter ; Korsós, Marietta Margaréta ; Grassalkovich, Anna ; Rakonczay, Zoltán

Abstract:

Heavy alcohol intake is one of the most common causes of acute pancreatitis (AP). We have previously shown that ethanol (EtOH) decreases the expression and activity of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a key role in alcohol‐induced AP development. The prescription drug, Orkambi (a combination of ivacaftor and lumacaftor) can correct impaired CFTR function and expression in cystic fibrosis (CF) patients. Thus, the present study aimed to investigate whether Orkambi can mitigate alcohol‐induced AP. Intact guinea‐pig pancreatic ducts were pre‐treated with different concentrations of ethanol (EtOH; 30, 50 and 100 mm) for 12 h alone or in combination with ivacaftor (VX770) and/or lumacaftor (VX‐809), and CFTR expression and activity were evaluated by immunostaining and by the patch clamp technique, respectively. Alcoholic AP was induced in Orkambi‐treated guinea‐pigs, and standard laboratory and histological parameters were measured. Ivacaftor and lumacaftor alone or in combination dose‐dependently restored the apical expression and activity of CFTR after EtOH treatment in vitro. Oral administration of Orkambi reduced the severity of alcohol‐induced AP and restored impaired CFTR activity and expression. Orkambi is able to restore the CFTR defect caused by EtOH and decreases the severity of alcohol‐induced pancreatitis. This is the first in vivo pre‐clinical evidence of Orkambi efficacy in the treatment of alcohol‐induced AP. image

Key points:

Acute pancreatitis is one of the leading causes of hospital admission among gastrointestinal diseases in which the lack of a specific drug therapy plays a crucial role.The cystic fibrosis transmembrane conductance regulator (CFTR) plays an essential role in pancreatic ductal HCO3– secretion; inappropriate CFTR function, as seen in heavy alcohol consumption, increases the risk of pancreatitis development.CFTR modulators are able to prevent the inhibitory effect of ethanol and reduce pancreatic ductal injury and the severity of alcohol‐induced pancreatitis.CFTR modulators present a novel option in the pharmacotherapy of alcohol‐induced pancreatitis by enhancing pancreatic functions or preventing recurrence.

2024-05-01·Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

Subtherapeutic triazole concentrations as result of a drug-drug interaction with lumacaftor/ivacaftor

Article

作者: van der Sijs, H ; Ruijgrok, E J ; Smeets, T J L ; de Winter, B C M ; Janssens, H M

Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy.

2024-03-01·Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

Elexacaftor/tezacaftor/ivacaftor improves chronic rhinosinusitis detected by magnetic resonance imaging in children with cystic fibrosis on long-term therapy with lumacaftor/ivacaftor

Article

作者: Schenk, Jens-Peter ; Wuennemann, Felix ; Zhao, Shengkai ; Sommerburg, Olaf ; Becker, Johanna K Z ; Graeber, Simon Y ; Alrajab, Abdulsattar ; Baumann, Ingo ; Eichinger, Monika ; Kauczor, Hans-Ulrich ; Chung, Jaehi ; Mall, Marcus A ; Stahl, Mirjam ; Wielpütz, Mark O ; Wucherpfennig, Lena ; Seitz, Angelika

INTRODUCTION:

Previous studies using magnetic resonance imaging (MRI) demonstrated early onset and progression of chronic rhinosinusitis (CRS) from infancy to school age, and response to lumacaftor/ivacaftor (LUM/IVA) therapy in children with cystic fibrosis (CF). However, the effect of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CRS detected by MRI in children with CF and at least one F508del mutation, and potential incremental effects of ELX/TEZ/IVA compared to LUM/IVA in F508del homozygous children have not been studied.

METHODS:

30 children with CF with at least one F508del mutation underwent three longitudinal paranasal sinus MRI before (MRI1), without (n = 16) or with LUM/IVA therapy (n = 14, MRI2), and with ELX/TEZ/IVA therapy (MRI3, mean age at therapy initiation 11.1 ± 3.4y, range 6-16y). MRI were evaluated using the CRS-MRI score.

RESULTS:

After therapy initiation with ELX/TEZ/IVA, the prevalence and in maxillary and sphenoid sinuses the dominance of mucopyoceles decreased (35% vs. 0 %, p<0.001 and 26% vs. 8 %, p < 0.05, respectively). This leads to a reduction in mucopyocele subscore (-3.4 ± 1.9, p < 0.001), and sinus subscores in MRI3 (maxillary sinus: -5.3 ± 3.1, p < 0.001, frontal sinus: -1.0 ± 1.9, p < 0.01, sphenoid subscore: -2.8 ± 3.5, p < 0.001, ethmoid sinus: -1.7 ± 1.9, p < 0.001). The CRS-MRI sum score decreased after therapy initiation with ELX/TEZ/IVA by -9.6 ± 5.5 score points (p < 0.001). The strength in reduction of mucopyoceles subscore and CRS-MRI sum score was independent of a pretreatment with LUM/IVA from MRI1-MRI2 (p = 0.275-0.999).

CONCLUSIONS:

ELX/TEZ/IVA therapy leads to improvement of CRS in eligible children with CF. Our data support the role of MRI for comprehensive monitoring of CRS disease severity and response to therapy in children with CF.

项与依伐卡托/芦马卡托相关的新闻（医药）

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

2024-10-21

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高价罕见病药未能纳入医保的原因分析

☝ 点击上方一键预约 ☝ 最新最热的医药健康新闻政策据统计，目前已有80多种罕见病药被纳入医保，未纳入的主要是一些高价罕见病药。笔者认为，主要原因是罕见病药的不合理高价与医保基金要求高效使用之间存在矛盾。从根本上说，患者才是医药服务真正的、最终的需求者和消费者，只是因为与医药机构相比，个人的力量太过单薄，并且医药方面的专业知识储备严重不足，所以才需要医保部门通过汇聚人民群众的缴费形成医保基金、并利用由此所产生的强大的集团购买力，为人民群众购买较高性价比的医药服务，实现医保基金对医药服务的战略性购买。这是医保基金购买医药服务的底层逻辑，决定了医保部门非常重要的一项任务就是提高医保基金的使用效率。反观一些高价罕见病药，患者每年的药费开支动辄百万、几百万甚至上千万元，其定价的合理性其实是值得商榷的。从根本上说，任何一种商品的价格都必须遵从如下等式，即：商品价格×所有该商品购买者的购买数量之和=成本（研发成本+生产成本+教育培训成本+销售成本）+利润。也就是说，商品价格=〔成本（研发成本+生产成本+教育培训成本+销售成本）+利润〕/所有该商品购买者的购买数量之和。参照安朴在《浅议罕见病用药定价的认知误区》一文中的理论阐释，我们将利用上述等式来分析一下，部分罕见病药的高定价是否合理的问题。 ——研发成本有研究发现，与其他创新药品研发成本相比，罕见病药的研发成本并非普遍昂贵。2019年，Aidan Hollis等国际知名学者以美国食品和药品监督管理局（US FDA）在2000年1月到2015年12月期间审批通过的创新药作为研究样本，随机抽取100种罕见病药和100种非罕见病药进行对比分析。结果表明，每一种最终获批的非罕见病药平均研发成本约为2.91亿美元，而同期罕见病药平均研发成本仅为1.66亿美元，远没有贯宣中那么高。另外，从国际上创新药研发模式来看，一个基本趋势是创新药研发越来越分散化。许多医药领域突破性的创新都来自小型制药企业，而大型医药企业则拥有庞大的患者群体、丰富的临床资源和试验经验。两者联手，不仅可以提高研发效率、摊薄研发成本，也可以降低单家企业自研失败的风险，从而减轻企业的研发负担。正因为如此，并购已经成为大型医药企业获得创新药品所有权的一种主流方式。比如，2009年默沙东以411亿美元收购美国先灵葆雅公司后，继续推进Keytruda项目的研究，2014年Keytruda成为获得美国FDA批准上市的首个PD-1抑制剂，2020年就实现了Keytruda单品营收144亿美元，贡献了公司药品销售总额的33%。 ——生产成本有观点认为，由于罕见病患者数量少，接受治疗的患者更少，导致生产线无法跟常规药品一样进行大规模量产，导致生产成本较高。需要指出的是，我国是一个人口大国，人口基数大，尽管罕见病在人群中的发病率较低，但罕见病患者的总人数仍然相当可观。据相关数据显示，中国已知的罕见病种类约有1400种，罕见病患者群体已超过2000万人，这是一个庞大的数字。再说，多数罕见病用药具有患者依从性高、需求刚性大、用药周期长（多数为终身用药）、市场竞争少的特点，从某一个时点来看，患者数量有限；但长期看，如果罕见病患者能够得到及时的对症用药，生命就能得到有效延续，累积的患者人数会不断增加，用药量也会越来越多，从而为药品的规模化生产、进而降低生产成本奠定基础。以治疗脊髓性肌萎缩症（SMA）的药物诺西那生钠注射液为例，该药品进入医保后即实现了迅速放量。从受益患者数量看，2022年1-5月覆盖患者数超过2000人，是进入医保前的5倍多，也超过了2021年底罕见病联盟在全国登记的患者总数。 ——教育培训成本罕见病具有单病种发生率低、诊断率低等特点，加上我国多数医务人员缺乏罕见病相关的临床经验，难以实现及时、准确诊断，从而影响了罕见病药的市场推广。为此，需要对医疗专业人员进行知识普及与宣传，这也导致企业在罕见病领域的教育培训成本要远高于普通药品的教育培训成本。近年来，随着国家对罕见病的重视和各方面投入力度的加大，这部分成本明显降低。国家卫健委开发和制作多种健康素养宣传材料，并通过传统媒体和新媒体进行推广，向公众提供科学、准确的健康科普信息，其中包括罕见病信息。同时，相关部门充分发挥专家作用，通过讲座、直播、公益广告等多种形式，提升医务人员相关知识储备。如，协和医院牵头成立国家罕见病医疗质量控制中心，既致力于普及罕见病诊断技术，也致力于罕见病患者登记与管理，有效改善了我国不同区域罕见病诊疗质量差别较大，患者误诊、漏诊率较高等问题。上述一系列举措，有效提升了医务人员的罕见病知识素养，也间接降低了企业的教育培训成本。 ——销售成本此前，多数企业在药品营销上的花费要远超研发费用，高者甚至达两倍之差。例如，2021年赛诺菲公司、艾伯维公司、武田制药公司在营销方面的投资分别为100.33亿美元、123.49亿美元和65.59亿美元，而他们在研发方面的投资分别为59.77亿美元、70.84亿美元和38.93亿美元，销售成本和研发成本的总比例约为1.7:1。现在，政策规定，医保药品目录实行全国统一并进行动态调整，创新药通过谈判或竞价进入医保，实行“双通道”管理和“零差率”销售，带金销售的空间越来越小，医保基金的战略购买作用得到越来越充分的发挥，大幅减轻了企业的营销负担，极大地降低了企业的销售成本。 ——药品利润虽然罕见病用药的研发、生产、销售等总体成本较高，但罕见病行业的利润并不低。有研究发现，罕见病药的毛利率超过80%，远超制药行业16%的平均水平。但相关企业认为，罕见病用药的利润率之所以会高于普通药品，是因为受众群体少导致利润绝对额难以与普通药品比较。 2019年，Aidan Hollis博士对Vertex公司拒绝进入英国NHS的两款药品（Kalydeco和 Orkambi）进行了针对性研究,并基于公司报表数据进行了测算，结果表明Vertex公司仅这两种药品的利润率最高估算值可达275%，利润率中间值估算值为129%。由于相关企业在宣传中只着重强调药品的高成本及其合理性，对药品定价可能存在的超高利润和巨额回报避而不谈，极大影响了公众对罕见病药物定价的正确认知。 ——用药数量从前面的分析可知，罕见病的用药数量，短期看，患者数量可能有限；但长期看，市场空间仍较可观，随着累积的罕见病患者数量的不断扩大，基于罕见病患者用药依从性，用药数量只可能越来越大，并且会大幅增加。 ——结论通过分析，我们可以看出：在前面所列的价格公式中，分子具有较大的压缩空间，而分母则有不断扩大的趋势。也就是说，高价罕见病药存在较大的降价空间，其超高定价并不合理！部分罕见病药之所以还能够实行高定价，根本原因并非通常所说的成本高和患者人数少，而是部分罕见病药的稀有性促成了企业垄断地位的形成，药品一旦上市就意味着充足的市场占有率和强势的定价话语权，企业利用其垄断地位实行高定价，而市场竞争的缺乏又保证了高定价的持续。但是，医保基金高效使用的内在要求客观上限制了高价罕见病药进入医保。作为高价罕见病药生产企业来说，需要站在一个更加宏观的角度，特别是针对中国这个拥有庞大人口基数的国家来说，应当认真审视罕见病药物定价的影响因素，更加理性地将药物价格控制在一个合理的范围内，真正实现医保基金可持续、企业获得合理利润回报和罕见病患者用药可及，进而形成三方共赢格局。（来源:海聊清谈作者:蔡海清) 药闻康策新媒体矩阵微信公众号点击下方一键关注【免责声明】 1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、点赞、点在看

并购医药出海申请上市

2024-09-19

·药渡

卖多少药，Biotech才能不亏钱？

©氨基观察-创新药组原创出品作者 | 武月盈利问题，如同达摩克利斯之剑般悬挂在每一家biotech的头顶。放眼国内市场，所有的公司都在为此努力，开源节流、降本增效，甚至有的公司开展全员BD、砍管线、转型CDMO。残酷的是，大多数biotech，还在寻找并努力靠近自己的盈亏平衡点。那么，究竟卖多少药，biotech才能不亏钱？我们不妨把视线放到海外，观察那些成功的过来者，走过的路。关于biotech的盈亏之问，看起来没有标准答案。有的企业，在其营收接近25亿美元才实现扭亏为赢；大部分，重磅品种上市后5年以上，销售额达到10亿美元以上才得以扭亏；而也有的企业，在营收仅2.6亿美金时已经顺利“上岸”。 / 01 / 5年、10亿美元放眼全球，biotech都是一个“新陈代谢”极高的群体。据广发证券统计数据显示，1990年以来，超过600家biotech企业在纳斯达克IPO。但截止2020年6月30日，仅有12家biotech有相对稳定的收入和正向现金流。将时间线拉长，从上世纪80年代biotech概念兴起至今，40年时间里，靠自己买迈入pharma阵营的，更是只有寥寥无几。为什么biotech很难长久地活下去？这是由商业模式决定的。相比成长性一般但胜在确定性强的大药企，biotech则是发散性创新模式，成长过程充满了不确定性。换句话说，由于研发的高风险和销售的不确定性，大多数biotech压根没法跑通商业模式，盈利更是无从谈起。那么，那些全球顶尖biotech，是如何上岸的？又为此付出了多大的代价？无论再生元、吉利德还是福泰制药、渤健，大都是在重磅品种上市后5年以上，销售额达到10亿美元以上才得以扭亏。以再生元为例，2008年推出首款药物Rilonacept后，由于适应症限制，销售额一直不理想，亏损也在不断扩大。直到2011年，再生元推出眼科神药Eylea，销售额迅速起飞，上市第一年销售额达8.4亿美元，第二年便成为重磅炸弹药物，带动公司整体营收达13.78亿美元，并顺利扭亏。吉利德的商业化故事起步于抗病毒药物Cidofovir，1996年上市后，销售额一直维持在1-2亿美元左右，直到2001年HIV重磅药物Tenofovir上市，销售额在3年内迅速突破10亿美元大关。在重磅炸弹的带领下，吉利德于2007年成功扭亏，此后盈利水平一路飙升。对比之下，福泰制药、渤健的盈利则花了更长时间。后者治疗多发性硬化症的重组干扰素1996年就上市，近十年后销售额18亿才得以扭亏；福泰制药命途更是多舛，从1999年的免疫抑制剂再到HIV，再到2011年的丙肝抗病毒疗法，福泰制药经过了20年的试错，其中替拉瑞韦首年销售额超过5亿美元，远超过市场预期。福泰制药也因为这款药物，首次实现了盈利。本以为公司命运能够就此逆转，但两年后，吉利德推出了一款丙肝神药 Sovaldi，能够彻底治愈丙肝，公司的抗病毒条线遭到了无情的毁灭性打击。最后在囊性纤维化这片应许之地，2012年推出Kalydeco、2015年推出Orkambi，才稳住局面。直到2017年，福泰制药才彻底走向盈利大道，当年其营收接近25亿美元。 / 02 / 更早的盈利从这些顶级biotech的盈利之路，不难看出，推出重磅炸弹后，平均要在10亿美元以上的收入，才能跨过盈亏平衡点。当然，翻看海外其他叫得上名号的biotech历年财报，你会发现，这里还有其他情况。比如，专注罕见病领域，并被阿斯利康以390亿美元收购的Alexion制药，营收达到仅仅2.6亿美金时已经扭亏为盈。这与Alexion制药的研发策略密切相关。公司的核心产品是全球首个上市的C5补体抑制剂，eculizumab。或许是因为该靶点开发难度巨大，该领域的竞争显得并不那么激烈。 2007年3月，FDA批准eculizumab，用于治疗阵发性睡眠性血红蛋白尿症（PNH）。随后又获批典型溶血性尿毒综合征(aHUS)、乙酰胆碱抗体阳性重症肌无力等适应症，并获得了多项孤儿药资格认证。 Eculizumab全球销售额一路飙升，2012年以11.24亿美元的销售额步入重磅炸弹梯队，2017年达31.44亿美元。从作用机制上来看，C5补体抑制剂理论上在类风湿性关节炎、银屑病、心脏病炎症并发症等风湿免疫性疾病领域均有较大潜力。公司早期也在这些领域做了大量研究。然而，事与愿违，在经历一系列的临床试验之后，eculizumab对类风湿性关节炎和膜性肾病的治疗效果均未达预期。相反，其在PNH领域展现出不错的效果。Alexion也借此转变阵地至罕见病领域。令人意想不到的是，这个金矿非常耐挖。正如Alexion创始人所说：与那些患者群达几万、几十万的非罕用药面临的价格压力相比，Alexion开发的药品多年来几乎不受影响。尽管eculizumab每年的用药费用高达44万美元，但由于其疗效确切及不可替代性，保险公司和国家性医保机构都愿意为其买单。守着这样一座“金山”，Alexion的研发投入很明显低了一个档次。被收购前，Alexion 2017年的研发费用率最高，不过也仅有25%。当年，其营收超35亿美元，只有6个产品，其中3个已上市，临床I期、II期、III期的产品各一个。看惯大药企动辄数十甚至上百的产品管线，Alexion的产品线显得单薄得多。而随着营收的增长，Alexion的研发费用率更是下降至16%左右。远低于同期，再生元等动辄30%的研发费用率。当然，研发费用率低，也与Alexion更青睐并购有关。2017年上市的3款产品中，2款来自于并购。这与吉利德有些类似。吉利德2007年首次盈利，净利率便超过30%，随后多年一直保持着这样的盈利水平，似乎并不存在盈利爬坡的困扰。 2001年，吉利德首个抗艾滋病药物替诺福韦酯获得FDA批准。而就在一年之后，吉利德耗资4.64亿美元收购Triangle制药，获得emtricitabine。以后来者眼光看，正是对于emtricitabine的收购，让吉利德在HIV领域迅速成为龙头企业。丙肝神药 Sovaldi也是通过收购Pharmasset公司获得的。2012年，吉利德耗资110亿美元收购Pharmasset，在2014年上市后的前3个月，Sovaldi就创造了23亿美元的惊人数据，创下当时美国新药上市的销售纪录。一个共识是，即使销售额再高，药企也必须保持着研发烧钱的属性。典型如再生元，Eylea挣来的钱几乎全被扔回了研发，金额比同期biotech高出一个数量级，因此，其在商业化的前十年盈利水平都并不高。而Alexion制药、吉利德等依托并购路径成长的企业，要么能够实现更早的盈利，要么能够更早实现高质量的盈利。 / 03 / “反面”教材当然，在头部biotech阵营，也并非没有“反面”教材。所谓“反面”是指，即使公司产品的销售额已经不低，但由于研发投入体量巨大，使得公司盈利还遥遥无期。典型如被辉瑞428亿美元收购的ADC元老Seagen。早在1997年，ADC技术尚未成熟时，Seagen就成立并瞄准ADC领域。经过20多年的探索，如今Seagen建立了一条优质的ADC产品管线。目前，Seagen共有四款产品上市，分别为Adcetris、Padcev、Tivdak、Polivy。2022年，这四款产品为Seagen带来了17亿美元的收入，占总营收的87%。同一年，Seagen的研发费用达到13.4亿美元，研发费用率接近70%。加之销售费用，公司全年亏损超过6亿美元。事实上，Seagen的商业化能力并不算差，但公司持续不断砸钱在平台和后续管线搭建，导致亏损不断放大。2018年，其研发费用率达到86%，尽管随着收入的增长，费用率有所下降，但依然接近70%，亏损额也由2.6亿美元扩大至6.1亿美元。这也不难理解。面对DS-8201带来的巨大压力，Seagen必须要用更多投入换回领跑机会。就在去年9月，害怕被颠覆的Seagen，还与PROTAC领域的领军企业Nurix达成了总价高达34.6亿美元的合作，希望研发出具有新作用机制的降解抗体偶物（DAC）。投入与冒险还在继续。再比如RNAi赛道领头羊Alnylam，自2018年推出全球第一款获批上市的RNAi药物，验证了RNAi技术路线；如今，手握5款上市的RNAi药物，销售额持续攀升；股价也一路高歌猛进，市值超过340亿美元，成功完成阶级跃迁。去年，靠着销售额及授权收入，Alnylam的营收更是首次超过百亿人民币，今年上半年继续保持超80%的高增长，营收超过80亿元，然而，公司仍在持续亏损。为了维持领先地位，Alnylam不得不持续投入研发，验证自家平台的价值，这也使得公司的研发投入居高不下，2023年至2021年，研发费用率分别为55%、85%和94%。同时，由于多款药物同时销售，公司的销售和管理费用率也一直维持在较高水平，过去三年分别为44%、74%和74%。这些因素，共同导致了公司迟迟无法盈利。当然，好消息是，随着Alnylam营收的快速增长，各项费用正在迅速被摊薄。也就是说，Alnylam仍走在通往盈利的道路上，只不过，用时长了些。 / 04 / 总结研发与商业化，对于创新药企同样重要。而过高的费用水平，会构成企业从销售盈利到整体盈利之间的鸿沟。如何在保持研发竞争实力的同时，提高销售额、摊薄费用率，是一门学问。对于国内正在奋力前行的biotech来说，学习这些成功案例不仅能够更好地理解行业规律，还能够为其在未来的道路上提供宝贵的经验借鉴。毕竟，在这个充满挑战的领域中，每一个成功的例子都是通往成功的宝贵财富。而那些成功者的盈利轨迹，或许也能让市场，更客观、理性地看待biotech的盈利问题。药渡媒体商务合作媒体公关 | 新闻&会议发稿张经理：18600036371（微信同号）点击下方“药渡“，关注更多精彩内容免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇

IPO财报

100 项与依伐卡托/芦马卡托相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	依伐卡托/芦马卡托	R07AX30	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
囊性纤维化	美国	Vertex Pharmaceuticals, Inc.	2015-07-02

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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


NCT04235140 (CTgov)	临床3期	囊性纤维化	52	LUM/IVA	顧鹹遞繭襯築夢鏇鑰廠(獵艱選觸醖願餘醖鏇窪) = 鹹淵鑰衊淵獵餘醖網膚鑰鑰窪築壓網醖鏇範糧 (鬱範選鹹遞鑰選齋鹽構, 糧範顧廠願襯窪顧積簾 ~ 網網艱網艱廠願網糧夢) 更多	-	2024-09-19
ERS2022	N/A	囊性纤维化 F508del	-	LUM/IVA cohort (US)	-	-	2022-09-04
				LUM/IVA cohort (UK)
ATS2022	N/A	囊性纤维化	-	Lumacaftor/Ivacaftor	糧廠願鑰鏇憲鹹齋築鹹(築齋醖艱齋襯襯艱積鏇) = 鏇廠壓糧願蓋積構製繭醖鑰廠蓋鏇繭鑰網簾艱 (廠遞願繭艱窪範鹹鹹顧 ) 更多	-	2022-05-15
				Lumacaftor/Ivacaftor (Control (no modulator))	糧廠願鑰鏇憲鹹齋築鹹(築齋醖艱齋襯襯艱積鏇) = 衊醖醖醖醖廠願夢遞餘醖鑰廠蓋鏇繭鑰網簾艱 (廠遞願繭艱窪範鹹鹹顧 ) 更多
NCT03625466 (CTgov)	临床2期	囊性纤维化	51	Placebo (Part 1: Placebo)	繭憲窪鏇繭窪糧積醖蓋(廠艱廠壓壓築鹽遞範築) = 壓鑰憲鬱鹹膚製餘齋顧積鹽鏇鑰繭願鬱遞築鬱 (窪蓋膚鑰簾願鬱衊衊鹹, 夢積鬱廠壓夢獵獵築簾 ~ 齋齋餘遞襯淵鬱鹽壓網) 更多	-	2021-12-08
				LUM/IVA (Part 1: LUM/IVA)	繭憲窪鏇繭窪糧積醖蓋(廠艱廠壓壓築鹽遞範築) = 築築蓋鏇範簾鬱遞夢簾積鹽鏇鑰繭願鬱遞築鬱 (窪蓋膚鑰簾願鬱衊衊鹹, 選製鑰觸餘鏇鑰鏇鏇築 ~ 獵構製壓衊製願積鏇餘) 更多
ERS2021	N/A	囊性纤维化 F508del	-	LUM/IVA	窪膚觸鏇製鹹獵夢膚鏇(選選選糧餘憲選遞顧鹹): OR = 0.16 (95% CI, 0.07 ~ 0.38) 更多	-	2021-09-05
				lumacaftor/ivacaftor (LUM/IVA)
NCT03061331 (Pubmed \| J Cyst Fibros) 人工标引	临床2期	囊性纤维化 A455E-CFTR Mutation	20	Placebo+Ivacaftor+Lumacaftor	醖淵夢構憲膚鹹艱憲鏇(選蓋獵餘範簾遞廠獵餘) = 襯顧網醖觸遞醖築醖廠範膚遞蓋製艱糧選蓋憲 (鏇憲衊築鏇淵網餘廠繭 )	不佳	2021-09-01
				Placebo+Ivacaftor+Lumacaftor	醖淵夢構憲膚鹹艱憲鏇(選蓋獵餘範簾遞廠獵餘) = 願膚憲壓餘願襯鑰製網範膚遞蓋製艱糧選蓋憲 (鏇憲衊築鏇淵網餘廠繭 )
NCT03125395 (VX16-809-116, Pubmed \| Lancet Respir Med) 人工标引	临床3期	囊性纤维化 F508del mutation	57	Ivacaftor/Lumacaftor	憲衊醖鹽遞顧蓋鬱獵構(網鹽淵簾繭憲膚範鏇壓) = 遞積廠齋簾鏇鏇顧糧鏇糧觸製夢窪憲築鑰衊艱 (積網壓遞艱蓋壓醖襯顧 ) 更多	积极	2021-09-01
NCT02807415 (Pubmed)	N/A	囊性纤维化	30	Lumacaftor-Ivacaftor	餘遞淵蓋構鏇廠鏇鑰獵(廠鹽廠願齋襯糧願鹽蓋) = 鑰鹹獵糧願獵築築鹹鏇夢構餘簾餘襯遞繭遞獵 (範醖淵網築齋衊壓築膚, -938.7 ~ 290.4)	-	2021-02-18
ERS2020	N/A	囊性纤维化 Phe508del mutation	5	Lumacaftor/Ivacaftor therapy	齋繭遞鹹繭艱繭衊顧餘(選鬱艱鹽觸蓋構範窪糧) = 獵壓餘衊鏇膚艱願齋簾窪顧膚糧鹽襯觸餘齋膚 (製構餘糧醖網選製願廠, 24.9 ~ 38.4)	-	2020-09-07
NCT03125395 (VX16-809-116, CTgov)	临床3期	囊性纤维化	57	LUM/IVA	鏇齋壓製醖憲簾艱餘製(憲壓衊衊觸鑰觸醖糧築) = 淵衊網廠醖衊鬱糧窪鬱選鏇壓繭夢淵夢選蓋壓 (襯窪醖醖夢襯夢鑰鬱願, 積蓋鏇遞鹹選糧遞繭願 ~ 網夢網繭襯衊簾鏇鬱膚) 更多	-	2020-08-07