Open-label, Single-arm, Non-controlled Trial to Evaluate Safety and Tolerability of Treprostinil Sodium in Children Below the Age of 18 Years Diagnosed With Pulmonary Arterial Hypertension (PAH)

The goal of this clinical trial is to evaluate safety and tolerability of preservative-free parenteral treprostinil in paediatric patients with PAH (PH Group 1) who are below 18 years of age. The main question it aims to answer is:
• if preservative-free parenteral treprostinil is safe and tolerable in the treatment of paediatric PAH in patients who are either treatment-naïve or have been previously treated with commercially available parenteral treprostinil formulations.
Participants will receive either subcutaneous (SC) or intravenous (IV) preservative-free treprostinil and will be observed for 5 months (20 weeks ± 1 week).

开始日期2024-05-01

申办/合作机构

Aop Orphan Pharmaceuticals GmbH

NCT06129240 / RecruitingN/A

An Open-Label ProSpective MultiCENTer Study to Evaluate Safety and Tolerability of Dry Powder Inhaled Treprostinil in Pulmonary Hypertension

Study LTI-401 is an open-label, multicenter study which will evaluate the safety and tolerability of LIQ861 in subjects who have WHO Group 1 & 3 PH.

开始日期2023-12-28

申办/合作机构

Liquidia Technologies, Inc.

100 项与曲前列尼尔相关的临床结果

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100 项与曲前列尼尔相关的转化医学

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100 项与曲前列尼尔相关的专利（医药）

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706

项与曲前列尼尔相关的文献（医药）

Thorax

Use of inhaled treprostinil in patients with interstitial lung disease and pulmonary hypertension: to boldly go where no other pulmonary vasodilator has gone before?

作者: Wort, Stephen John ; Piccari, Lucilla

2024-01-01·ERJ Open Research

Severe pulmonary hypertension–interstitial lung disease presenting as right ventricular failure: stabilisation with intravenous prostacyclin and maintenance with inhaled prostacyclin

Article

作者: Farber, Harrison W ; Moallem, Niala ; Sharofi, Aldo ; Fiscus, Garrett ; Parikh, Raj ; Thomas, Alysse

Background:

Pulmonary hypertension (PH) leads to increased morbidity and mortality in interstitial lung disease (ILD). While the INCREASE trial highlighted the use of inhaled prostacyclin in PH-ILD patients, such therapy may be inadequate when right ventricular failure (RVF) is also present. In this study, we report the use of intravenous prostacyclin in three PH-ILD patients to stabilise right ventricular (RV) function, with a subsequent transition to maintenance therapy with inhaled prostacyclin.

Methods:

We evaluated three consecutive PH-ILD patients with RVF. RV afterload and pulmonary vascular resistance (PVR) were treated with intravenous prostacyclin during the induction phase of the therapy. Patients transitioned from intravenous prostacyclin to the maintenance phase of the treatment with inhaled prostacyclin once three transition criteria were met: cardiac index (CI) >2 L·min−1·m−2, PVR <7 Wood units (WU) and tricuspid annular plane systolic excursion (TAPSE) change >1 mm or TAPSE >1.6 cm.

Results:

Pre-treatment parameters for the three patients were a mean PVR of 14.3 WU, a mean Fick CI of 1.8 L·min−1·m−2and a mean TAPSE of 1.4 cm. The average intravenous prostacyclin dose at the time of transition to maintenance therapy was 20.7 ng·kg−1·m−2of treprostinil. At 3-months follow-up, the mean PVR was 6.3 WU, Fick CI 2.2 L·min−1·m−2and TAPSE 1.7 cm.

Conclusion:

This case series of three PH-ILD patients with RVF introduces the concept of an initial intravenous prostacyclin induction phase, followed by a transition to maintenance therapy with inhaled prostacyclin. Further development of this treatment algorithm with a refinement of the transition criteria, potential testing in a clinical trial and a longer-term follow-up period is warranted to improve the outcomes of advanced PH-ILD patients with concomitant RVF.

2023-12-31·Journal of Medical Economics

Hospitalization-related costs associated with oral agents targeting the prostacyclin pathway for pulmonary arterial hypertension

Article

作者: Bilir, S Pinar ; McConnell, John ; Tsang, Yuen ; Xu, Yifan ; Panjabi, Sumeet

AIMS:

Pulmonary arterial hypertension (PAH) is a rare, progressive, and ultimately fatal form of the broader condition pulmonary hypertension. ESC/ERS guidelines recommend therapy targeting the prostacyclin pathway for patients not achieving low-risk mortality status. Currently, only oral selexipag (OS) and oral treprostinil (OT) have this mechanism of action and are available in the United States (US). A recent database analysis has shown significantly lower hospitalization risk for patients treated with OS versus OT. Nevertheless, differences in hospitalization and treatment costs among PAH patients taking oral prostacyclin pathway agents (PPAs) in the US healthcare system remain unclear. This study aims to estimate the difference in costs for patients who achieve a stable maintenance dose from a US payer perspective.

MATERIALS AND METHODS:

We developed a cost calculator including direct medical costs from the US third-party payer perspective to estimate PAH-related hospitalizations and costs associated with oral PPA use over 2 years, in a hypothetical US payer plan with 1 million members. The treatment-eligible population was estimated from real-world epidemiological data. Treatment-specific hospitalizations were estimated from a study using the Optum Clinformatics administrative claims database. Influence of each model parameter was tested in one-way sensitivity analyses (OWSA), while scenario analysis tested the impact of key assumptions.

RESULTS:

For 78 PAH patients included in the model, the base case scenario estimated total costs of $46,736,768 with 98 PAH-related admissions for OS, and total costs of $60,113,620 and 161 PAH-related admissions over 2 years for OT. Using OS was associated with 22.3% cost reduction and 39.1% hospitalizations averted; the number of patients needed treated with selexipag to avoid one hospital admission was 1.23. OWSA indicated medication cost was the most sensitive parameter, followed by population parameters.

LIMITATIONS AND CONCLUSIONS:

OS use over 2 years would result in lower total, drug, and hospitalization-related costs compared with OT, thus providing financial savings for payers.

126

项与曲前列尼尔相关的新闻（医药）

2024-04-22

·PRNewswire

Par Pharmaceutical Issues Voluntary Nationwide Recall of Seven Lots of Treprostinil Injection Due to Potential for Silicone Particulates in the Product Solution

DUBLIN, April 22, 2024 /PRNewswire/ -- Endo International plc announced today that one of its operating companies, Par Pharmaceutical, Inc. (Par), is expanding its voluntary recall to include seven lots of Treprostinil Injection 20mg/20mL (1mg/mL) to the consumer level. The product is being recalled due to the potential for the presence of silicone particulates in the product solution. Administration of an injectable product that contains particulate matter may result in local irritation or swelling in response to the foreign material. If the particulate matter reaches the blood vessels it can travel to various organs and block blood vessels in the heart, lungs or brain which can cause stroke and even lead to death. To date, Par has not received any reports of adverse events related to this recall. Treprostinil Injection is formulated for subcutaneous or intravenous infusion. The product is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension to diminish symptoms associated with exercise and for patients who require transition from epoprostenol to reduce the rate of clinical deterioration. Treprostinil Injection 20mg/20mL (1mg/mL) is distributed in 20mL multidose vials as sterile solutions in water for injection, individually packaged in cartons under NDC #42023-206-01. The following lots are affected by this recall: The lots were distributed nationwide to wholesalers and hospitals from June 16, 2022 through August 7, 2023. See labels of vials from the affected lots here. Par is providing written notification to wholesale accounts and the hospital location that have received the affected lot and is arranging for return of all existing inventory through Inmar, Inc. Wholesale distributors and hospital pharmacies that have the product being recalled should immediately discontinue use and stop distribution immediately. If you have further distributed the recalled product, please notify your accounts or any additional locations which may have received the recalled product. For information regarding the recall process, call Inmar, Inc. at 1-855-410-3565 Monday through Friday between the hours of 9 am and 5 pm EST. For medical or technical product information or to report a product complaint or adverse event please call 1-800-828-9393. Consumers should contact their physician or healthcare provider if they have experienced any problems that may be related to taking or using this drug product. Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax. Complete and submit the report Online: Regular Mail or Fax: Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 This recall is being conducted with the knowledge of the U.S. Food and Drug Administration. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation, including, but not limited to, statements with respect to the voluntary recall of Treprostinil Injection, the reasons for and the risks associated with the recall, the potential for adverse events and adverse event reporting, communications with and responses from regulators, and any other statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "outlook," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect the Company's current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of risk factors. Additional information concerning risk factors can be found in press releases issued by the Company, as well as public periodic filings with the U.S. Securities and Exchange Commission (the "SEC") and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K. SOURCE Endo International plc

2024-04-16

·BioSpace

United Therapeutics to Feature Clinical Data Across its Commercial and Development Portfolio at the American Thoracic Society 2024 International Conference

Initial, interim long-term data from the ongoing ralinepag phase 3 ADVANCE EXTENSION open label study to be presented at a poster discussion session An annual update of the preliminary baseline data from the TETON phase 3 studies of inhaled treprostinil in idiopathic pulmonary fibrosis will be presented at a poster session SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)--United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that recent research across its commercial and development portfolio will be presented at the American Thoracic Society (ATS) International Conference in San Diego on May 17-22, 2024. At ATS, United Therapeutics will host an educational industry theater on implementing treprostinil induction strategies in pulmonary hypertension, and the company is sponsoring the ATS 2024 Women’s Forum. “We look forward to presenting the latest data on several of our key products and development programs,” said Andrew Nelsen, PharmD, Vice President, Global Medical Affairs at United Therapeutics. “Notably, our academic and industry collaborators will present initial interim efficacy data from the ADVANCE EXTENSION open label extension evaluating extended-release ralinepag for pulmonary arterial hypertension and baseline data updates for the ongoing TETON studies in idiopathic pulmonary fibrosis. We are also pleased to unveil the exciting preliminary findings from our collaboration with Tempus, a leader in artificial intelligence and precision medicine, laying the foundation for earlier identification of patients with pulmonary hypertension.” Posters, mini-symposia, and discussion sessions include: Mini Symposium, Sunday, May 19, 10:03 to 10:15 a.m. PT: A14 – Metabolomic Signatures of Pulmonary Hypertension Associated with Interstitial Lung Disease: A Post-hoc Analysis of the INCREASE Study. Presented by Aaron B. Waxman, M.D., Ph.D., Brigham and Women’s Hospital. Thematic poster session, Sunday, May 19, 11:30 a.m. to 1:15 p.m. PT: A46/P829 – Pulmonary Hypertension Screening Strategies in Patients with Interstitial Lung Disease: A Survey of PHINDER Study Sites. Presented by Eric Shen, PharmD, United Therapeutics. Thematic poster session, Monday, May 20, 11:30 a.m. to 1:15 p.m. PT: B48/P1259 – TETON Phase 3 Clinical Trials of Inhaled Treprostinil in the Treatment of Idiopathic Pulmonary Fibrosis: Annual Update of Preliminary Baseline Data. Presented by Steven D. Nathan, M.D., Inova Fairfax Hospital. Thematic poster session, Monday, May 20, 11:30 a.m. to 1:15 p.m. PT: B48/P1260 – Study Design and Rationale for the TETON-PPF Clinical Trial of Inhaled Treprostinil for the Treatment of Progressive Pulmonary Fibrosis. Presented by Steven D. Nathan, M.D., Inova Fairfax Hospital. Thematic poster session, Tuesday, May 21, 11:30 a.m. to 1:15 p.m. PT: C62/P284 – Real-World Transition and Persistence to Oral Treprostinil Therapy from Parenteral Prostacyclins in Patients with Pulmonary Arterial Hypertension. Presented by Ali Ataya, M.D., University of Florida. Poster discussion session, Wednesday, May 22, 11:00 a.m. to 1:00 p.m. PT: D105/410 – Clinical Improvements with Parenteral Induction Therapy in Intermediate-High Risk Patients With PAH: A Sub-Group Analysis of the EXPEDITE Study. Presented by Chad Miller, M.D., Piedmont Healthcare. Poster discussion session, Wednesday, May 22, 11:00 a.m. to 1:00 p.m. PT: D105/420 – Initial Long-term Data from a Phase 3 Open-label Extension Study (ROR-PH-303) Evaluating Ralinepag for the Treatment of Pulmonary Arterial Hypertension (ADVANCE EXTENSION). Presented by Joan A. Barberà, M.D., Ph.D., Hospital Clinic de Barcelona. Poster discussion session, Wednesday, May 22, 11:00 a.m. to 1:00 p.m. PT: D102/502 – Structured EHR Data Underestimates Prevalence and Misses Large Proportions of Patients with Pulmonary Hypertension. Presented by RuiJun Chen, M.D., Tempus. Poster discussion session, Wednesday, May 22, 11:00 a.m. to 1:00 p.m. PT: D102/503 – A Novel Phenotyping Pipeline to Improve Identification of Patients with Pulmonary Hypertension in Electronic Health Records. Presented by David Vidmar, Ph.D., Tempus. Poster discussion session, Wednesday, May 22, 11:00 a.m. to 1:00 p.m. PT: D102/504 – ECG-based Machine Learning Model Identifies Patients at High Risk for Incident Pulmonary Hypertension. Presented by Greg Lee, Tempus. Sponsored events include: The ATS 2024 Women’s Forum, Monday, May 20, 11:45 a.m. to 1:15 p.m. PT featuring Zea Borok, M.D., ATSF, formerly of the University of Southern California; Stephanie Davis, M.D., ATSF, University of North Carolina at Chapel Hill; Sonia Buist, M.D, Oregon Health & Science University; and Obianuju Ozoh, M.D., University of Lagos. Industry Theater, Sunday, May 19, 12:30 to 1:00 p.m. PT – Implementing Treprostinil Induction Strategies in Pulmonary Hypertension. Presented by Chad Miller, M.D., Piedmont Healthcare. United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun, we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/pbc. Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of April 16, 2024, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason.

临床3期

2024-04-09

·同写意

富则思变，填平“默沙东悬崖”的新药

为打造全球ADC/RDC未来产业高地，成都医学城拟于2024年4月18日-19日举办首届未来XDC新药大会！大会以“共创偶联药物产业未来”为主题，由同写意策划，安排一场主论坛和九场主题论坛，邀请“政、产、学、研、金、媒”各领域专家，通过“成果发布、主题演讲、热点对话、表彰颁奖、展览展示”五位一体的多元化的组织形式，迸发更多XDC产业新科技、新业态、新模式，构建XDC产业全新生态，触摸医药产业未来脉动。拥有一款年销售额250亿美元的产品，对于开发商来有可能是把双刃剑。从当下来看，“花开堪折直须折”；从长远来看，“常将有日思无日”。坐拥当今药王Keytruda的默沙东就处在这样的位置。1默沙东心血管药物来得正及时如今的默沙东，一手“了却君王天下事”，收获着每年200多亿美元的药王销售，另一手却要展开Keytruda 2028年专利到期后“赢得生前身后名”的部署。尤其考虑到Keytruda的销售额占据了默沙东收入的40%以上，他们就更要奉行“听宽，好和牌”的策略。居安思危的紧迫感在2024年3月26日得到缓解，FDA批准了默沙东的肺动脉高压（PAH）疗法Winrevair（sotatercept-csrk）。分析师预测，这是一款年销售额峰值能够冲上70亿美元的药物。Sotatercept针对的肺动脉高压是一种罕见的疾病，在美国有大约4万名患者，最常见于 30 至 60 岁的女性。患者肺部小血管中的疤痕会抑制流向心脏右侧的血液。它会导致呼吸短促和疲劳，降低运动能力，如果不治疗可能致命。Sotatercept在一项关键试验中改善了患者的症状，降低了疾病进展和死亡的风险。Winrevair 是 FDA 批准的首个针对肺动脉高压的激活素信号抑制剂疗法，通过控制促增殖信号和抗增殖信号之间的平衡来调节患者动脉血管细胞增殖，也是第一种针对肺动脉高压根本病理的治疗方法。目前有几种药物用于治疗肺动脉高压，这些药物都是有助于扩张血管的血管扩张剂。强生的 Opsumit 和 Uptravi，以及 United Therapeutics 的 Tyvaso 都是针对这种情况的处方产品，但这些药物只能抑制症状，而不能治疗根本疾病。在获得了FDA的绿灯之后，默沙东接下来就要准备Winrenvair的上市工作了，他们已经为这款首创新药标出了为每瓶 14000 美元的价格。对于大多数患者（大约三分之二），他们将每三周使用一剂Winrenvair，相当于全年的费用高达24.2万美元（剂量基于体重，因此费用会有所差异）。默沙东首席执行官Rob Davis表示，Winrenvair将每年为公司带来几十亿美元的销售（Jefferies分析师预测其峰值销售额将达到75亿美元），并且有望继续扩大标签范围，进入更早期的治疗领域。如释重负的Davis做了一个形象的比喻，在Winrenvair问世之前，Keytruda的专利到期好似悬崖，而在Winrenvair应运而生之后，Keytruda的专利到期更像一座可以越过的小山。默沙东还与Bristol Myers Squibb 签订了许可协议。根据协议，BMS获得了在肺动脉高压领域以外开发和商业化Winrenvair的独家权利。2研发还是购买Winrenvair的成功再次引发了业内人士对于制药巨头发展策略模式的讨论。同Keytruda（默沙东2009年通过收购Schering-Plough先灵葆雅获得）类似，Winrevair也不是默沙东的嫡出。2021年，默沙东击败了包括BMS在内的竞争对手，斥资115亿美元收购了Acceleron Pharma，并将其PAH资产sotatercept并入了自己的管线。值得注意的是，默沙东在制药巨头中似乎是最舍得将钱投入研发的，他们在2023年的研发领域投入达到了惊人的305亿美元，这几乎是50名开外的药企全年销售额的10倍。相比于2022年的135亿美元，默沙东在去年增加了126%的研发投入。放眼全球药企，默沙东在研发方面的一掷千金也是远远领先竞争对手的，排在第二名的罗氏去年的研发投入只有不到150亿美元，尚不足默沙东的一半（图1）。图1. 全球药企2023年研发投入排名。（图片来源：Drug Discovery and Development）从投入比例来看，默沙东的走势图在制药巨头中也非常独特，他们将几乎一半的收入都投入了研发（图2）。需要指出的是，默沙东在研发方面的投入，包括了114亿美元收购Prometheus Biosciences（核心收购资产III期tulisokibart，自免疫疾病疗法），12 亿美元的收购Imago BioSciences（主要候选药III期bomedemstat，骨髓增生性肿瘤），以及于第一三共价值55亿美元的合作项目（ADC开发）。所以默沙东的惊人研发投入，在一定程度上也反映出了医药巨头越来越倚重“借鸡生蛋”的开发策略。而且默沙东在收购过程中非常看重后期资产，这一点从tulisokibart和bomedemstat身上就能得到明显体现。图2. 制药巨头研发投入比率示意图。（图片来源：Drug Discovery and Development）3默沙东模式，汝能持否？默沙东的研发模式即便在制药巨头中也显得独树一帜。从图2中不难发现，他们一直以来都是研发支出比例最高的制药公司之一。2022年，其研发投入135亿美元，仅次于罗氏的147亿美元。但到 2023 年，默沙东便将其研发支出大幅增加至 305 亿美元。前文提及，这种暴涨支出背后包含一系列重大投资，这些企业并购以及合作费用比 2022 年 6.9 亿美元的总费用大幅增加，2022年的费用与 Moderna、Orna Therapeutics 和 Orion 的合作和许可协议有关。与此同时，该公司2023年1.4%的收入增长明显低于2020-2022年的业绩，但这仍然确保了默沙东成为2023年度收入最多的大型制药公司（图3）。图3. 大型制药公司年收入走势对比图。（Drug Discovery and Development）鉴于默沙东“听宽好和牌”的研发管线，分析师普遍对他们的研发策略持适度乐观态度。默沙东继续多元化其肿瘤学重点，涵盖免疫肿瘤学、精准分子靶向和组织靶向，同时还扩展到疫苗、心脏代谢疾病和神经科学等新的治疗领域。他们对其管道产生背后蕴藏的收入潜力充满信心，特别是来自肿瘤学小分子、抗体药物偶联物以及与 Moderna 和第一三共等战略合作内容。图4. 默沙东市值走势图。（图片来源：companiesmarketcap.com）默沙东目前的市值已经达到了3178.9亿美元，一年内提升17.39%（2024年3月27日数值，图4）。其市值在制药领域排名全球第四，仅次于礼来（7367.4亿美元）、诺和诺德（5774.3亿美元）和J&J（3753.7亿美元）。4心血管疾病疗法：默沙东扩张策略的桥头堡如前文所述，默沙东的Keytruda一款药物为他们带来了40%多的收入，这对于公司的未来，尤其是Keytruda关键专利到期之后的发展带来严峻挑战。因此默沙东早以居安思危地展开了后Keytruda时代的战略部署。Winrevair 就是是默沙东产品组合扩张战略的基石。与之对应的是，心血管疾病领域的扩张将成为默沙东未来的核心策略之一。他们在这个领域本来就拥有悠久的历史，但资产影响力较小。Winrenvair的成功开发则令默沙东恍惚间念兹在兹地回到了从前。他们的第一款重磅炸弹药物Vasotec（enalapril）就是来自心血管疾病领域，1985年的平安夜针对高血压获得FDA的批准，并于三年后跻身重磅炸弹行列。1987年，默沙东又推出了第一款针对高胆固醇的商业化他汀类药物Mevacor（Lovastatin），并在此后开发了新一代他汀药物Zocor（Simvastatin）。可以在一定程度上说，默沙东是依靠心血管疾病疗法登堂入室的，如果再往前推，还可以追溯到1958年的高血压药物Diuril (chlorothiazide) 。默沙东的的一个重要战略目标，就是到 2030 年批准 8 种心血管疾病的适应症或新药，并实现 100 亿美元的收入。Winrevair的成功撞线标志着他们朝向这个目标迈出了坚实的一步。默沙东预计将 Winrevair 的使用范围扩大到更多 PAH 患者，并正在针对 III 类或 IV 类疾病的后期患者 (ZENITH) 和新诊断患者 (HYPERION) 进行 III 期试验，分别于 2025 年和 2026 年完成。默沙东管线内仍然有多款心血管疾病候选药：MK-0616模态：多肽适应症：高胆固醇血症阶段：III期（NCT05952856）作用机制：前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型(PCSK9) 抑制剂递送方式：口服高胆固醇血症是一种血液中 LDL（低密度脂蛋白）胆固醇水平升高的疾病，影响着美国约 8600 万成年人，其中近 2500 万人的总胆固醇水平非常高，超过 240 mg/dL。它是与 ASCVD （动脉粥样硬化性心血管疾病）的主要诱因，而 ASCVD 是美国和全球的主要心血管疾病死亡原因。调整饮食并采取他汀类药物治疗很多情况下并不足以维持正常LDL胆固醇水平。高 LDL 胆固醇如果不及时治疗，可能会导致心脏病和中风等 ASCVD 事件。PCSK9 通过调节 LDL 受体的水平在胆固醇稳态中发挥关键作用，LDL 受体负责细胞摄取胆固醇。PCSK9 的抑制可阻止 PCSK9 与 LDL 受体的相互作用。这导致细胞表面有更多的 LDL 受体，可以从血液中去除 LDL 胆固醇。MK-0616 是一种大环肽，可与 PCSK9 结合并抑制 PCSK9 与 LDL 受体的相互作用。MK-0616 是第一个口服 PCSK9 抑制剂，每日递送。MK-5475模态：小分子适应症：肺动脉高压阶段：II期（NCT04732221)作用机制：可溶性鸟苷酸环化酶 (sGC) 激动剂MK-2060模态：单抗适应症：血栓阶段：II期（NCT05027074）作用机制：抑制因子 XI 的激活和因子 XIA 的活性参考文献：1.FDA Approves Merck’s WINREVAIR™ (sotatercept-csrk), a First-in-Class Treatment for Adults with Pulmonary Arterial Hypertension (PAH, WHO* Group 1). Merck&Co. Press Release. 26. 03. 2024.2.Sebastian, D. Merck to Buy Acceleron Pharma for $11.5 Billion. WSJ. 30. 09. 2021.3.Loftus, P. Merck’s $11.5 Billion Bet on Its Next Big Drug Finally Arrives. WSJ. 26. 03. 2024.4.Gardner, J. FDA approves Merck lung disease drug acquired in $11B deal. Biopharma Dive. 26. 03. 2024.5.Muller, M. Merck Drug for Rare Form of High Blood Pressure Gets US Nod. Bloomberg. 26. 03. 2024.6.Merck Announces Fourth-Quarter and Full-Year 2023 Financial Results. Merck & Co. Press Release. 01. 02. 2024.7.Merrill, J. With Winrevair Approved, Merck Has A Chance To Execute On CV Strategy. 26. 03. 2024.8.Buntz, B. Why Merck shelled out $30B+ on R&D in 2023. Drug Discovery and Development. 11. 03. 2024.9.Buntz, B. Are Big Pharma giants getting the right ROI on their R&D investments? A visual exploration. Drug Discovery and Development. 08. 03. 2024.更多优质内容，欢迎关注↓↓↓

抗体药物偶联物专利到期

100 项与曲前列尼尔相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06213	曲前列尼尔	B01AC21	DB00374

研发状态

适应症	最高研发状态	国家/地区	公司
肺动脉高压	批准上市	中国更多	Baxter International, Inc. 更多
慢性血栓栓塞性肺动脉高压	批准上市	欧盟更多	SciPharm SARL 更多
间质性肺疾病	批准上市	美国更多	United Therapeutics Corp. 更多
肺性高血压	批准上市	美国更多	United Therapeutics Corp. 更多
特发性肺纤维化	临床3期	新西兰更多	United Therapeutics Corp. 更多

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临床结果

适应症

分期

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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


NCT04691154 (ATS2024) 人工标引	临床3期	肺动脉高压	15	L606	衊選窪廠襯獵憲顧顧願(壓鬱積夢糧獵獵艱艱繭) = 鏇廠鬱夢鑰衊顧衊鏇遞鹹獵鹹製願網窪選廠襯 (獵網鑰遞艱醖餘範網鏇 ) 更多	积极	2024-05-22
NCT02261883 (CTgov)	临床2期	新生儿持续肺动脉高压 \| 肺动脉高压	42	IV Remodulin (IV Remodulin)	醖選齋餘顧蓋顧憲簾蓋(鹽壓窪鹹構構夢構觸鬱) = 鑰獵餘願夢製淵襯衊壓餘淵艱鹽範積餘獵鏇蓋 (夢遞鹽築築鏇夢簾艱窪, 餘積製選願壓製窪範構 ~ 壓糧鹽繭製鹽醖鹹鹹鏇) 更多	-	2024-03-05
NCT02261883 (CTgov)	临床2期	新生儿持续肺动脉高压 \| 肺动脉高压	42	Placebo (Placebo)	醖選齋餘顧蓋顧憲簾蓋(鹽壓窪鹹構構夢構觸鬱) = 鏇醖餘襯願鏇憲衊鹽繭餘淵艱鹽範積餘獵鏇蓋 (夢遞鹽築築鏇夢簾艱窪, 襯範齋觸齋顧艱鹽願淵 ~ 築鬱窪製糧遞網醖醖衊) 更多	-	2024-03-05
NCT03794583 (CTgov)	临床3期	慢性阻塞性肺疾病 \| 肺性高血压	41	Treprostinil	窪齋襯繭廠糧醖鑰衊遞(願積醖構範廠夢膚齋選) = 觸簾獵願糧願選廠繭範選製願餘夢選獵衊鏇選 (範構簾簾鑰顧糧餘築襯, 範窪鹹範鏇觸繭糧繭繭 ~ 衊獵鏇淵鹹壓鑰憲顧鑰) 更多	-	2023-12-18
NCT03496623 (CTgov)	临床3期	慢性阻塞性肺疾病 \| 肺性高血压	188	Placebo solution	鹽壓艱獵鏇壓範鬱構襯(構糧醖網襯選繭襯簾糧) = 遞糧願築簾廠鏇壓襯衊範蓋齋構淵鑰蓋齋網窪 (膚膚淵鏇蓋範壓憲獵醖, 選蓋壓繭願衊蓋憲憲願 ~ 積淵願壓願夢壓觸積壓) 更多	-	2023-11-24
NCT05067270 (CTgov)	临床1期	注射部位反应 \| 1型糖尿病	40	insulin+magnesium chloride+treprostinil+sodium citrate+humalog (Treatment Given to Arm Region)	觸選醖憲簾齋構願夢夢(築夢觸鹹觸獵淵醖構醖): Geometric Least Squares Mean Ratio = 1.77 (95.0% CI, 1.3 ~ 2.4); Geometric Least Squares Mean Ratio = 1.49 (95.0% CI, 1.09 ~ 2.02); Geometric Least Squares Mean Ratio = 1.49 (95.0% CI, 1.1 ~ 2.03)	-	2023-10-04
NCT05067270 (CTgov)	临床1期	注射部位反应 \| 1型糖尿病	40	insulin+magnesium chloride+treprostinil (Treatment Given to Thigh)		-	2023-10-04
NCT03497689 (CTgov)	临床4期	肺动脉高压	36	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil	簾艱構醖獵製襯鬱顧憲(醖築糧網範願築網鹹壓) = 觸願鏇壓簾淵衊顧餘鏇衊選鹽鏇鹽選積餘顧襯 (積觸製夢糧鏇觸鬱選築, 廠範鬱鏇繭獵壓鹹鏇餘 ~ 鏇繭繭齋鏇觸選齋夢衊) 更多	-	2023-08-07
NCT02630316 (INCREASE study, Pubmed)	临床2/3期	间质性肺疾病	326	Inhaled treprostinil	夢艱淵願夢艱選壓鏇淵(網夢構壓艱遞製製齋獵) = 襯製獵膚鑰簾膚夢鑰衊鏇製遞糧簾餘積廠網襯 (衊窪壓選齋鹹夢遞觸膚 )	积极	2023-07-19
NCT02630316 (INCREASE study, Pubmed)	临床2/3期	间质性肺疾病	326	Placebo	鏇艱襯築蓋遞艱鹽齋艱(簾壓鑰選壓膚齋鬱鑰築) = 鬱醖網鹹廠糧淵構顧顧夢顧獵窪願願廠築簾築 (廠襯憲餘鏇繭艱膚獵觸 )	积极	2023-07-19
NCT02633293 (CTgov)	临床2/3期	肺性高血压 \| 间质性肺疾病 \| 合并肺纤维化和肺气肿	243	Inhaled Treprostinil	淵糧衊網鹽鹽廠顧繭鹽(壓鹹膚構鏇窪鬱醖製築) = 醖網顧願遞餘窪積鹹憲齋蓋築顧夢糧壓觸築衊 (壓蓋艱遞鬱餘醖鏇蓋壓, 選鹽鏇簾壓獵壓齋網願 ~ 齋鹽鏇選獵遞襯鑰觸窪) 更多	-	2022-12-02
NCT03497689 (EXPEDITE, Biospace) 人工标引	临床4期	肺动脉高压	36	Treprostinil	窪憲顧鏇鹽膚獵醖夢選(糧願簾壓積鏇範繭觸築) = 鑰鬱醖構簾膚觸鬱糧膚製蓋簾觸夢齋遞餘齋餘 (網築獵觸鹹鏇網膚蓋鬱 )	积极	2022-10-31
NCT02630316 (INCREASE, Pubmed)	临床2/3期	肺动脉高压	326	High dose inhaled treprostinil (≥9 breaths per session)	襯衊糧鬱窪獵醖膚製遞(壓築夢鏇廠淵夢鹽築膚) = 蓋醖選鏇壓範齋構襯襯壓鹽範鹹簾簾齋鹹願壓 (製艱選築積糧簾願鏇願 ) 更多	积极	2022-09-14
NCT02630316 (INCREASE, Pubmed)	临床2/3期	肺动脉高压	326	Low dose inhaled treprostinil (<9 breaths per session)	襯衊糧鬱窪獵醖膚製遞(壓築夢鏇廠淵夢鹽築膚) = 艱糧鏇襯網獵簾獵襯壓壓鹽範鹹簾簾齋鹹願壓 (製艱選築積糧簾願鏇願 ) 更多	积极	2022-09-14