A Single-center, Open-label, Fixed-sequence Trial to Investigate the Effect of Multiple-dose Aprocitentan on the Single-dose Pharmacokinetics of Combined Oral Contraceptives in Healthy Female Participants

The goal of this clinical trial is to learn if drug aprocitentan has an effect on hormonal contraceptives in healthy female volunteers. The main question it aims to answer is:
Does aprocitentan modify the fate of hormonal contraceptives in the body?
Trial participants will:
* Take a single dose of hormonal contraceptives (fixed combination) alone
* Take aprocitentan every day for 2 weeks
* Take a single dose of the same hormonal contraceptives at the same time as the 10th administration of aprocitentan.

开始日期2025-01-18

申办/合作机构

Idorsia Pharmaceuticals Ltd.

NCT05196399

/ Completed临床1期

A Single-center, Open-label, Randomized, Two-way Crossover Phase 1 Study to Compare the Single-dose Pharmacokinetics of Different Tablet Formulations of Aprocitentan in Healthy Subjects

The main purpose is to study the pharmacokinetics of aprocitentan (ACT-132577) using 2 different tablet formulations. The clinical pharmacology data will be used to determine bioequivalence of 2 different tablet formulations.

开始日期2022-02-02

申办/合作机构

Idorsia Pharmaceuticals Ltd.

NCT04252495

/ Completed临床1期

An Open-label Phase 1 Study to Investigate the Effect of Moderate Hepatic Impairment Due to Liver Cirrhosis on the Pharmacokinetics of a Single Dose of 25 mg Aprocitentan

This is a prospective, open-label, single-dose, Phase 1 study, to assess the effect of moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of aprocitentan (ACT-132577).

开始日期2020-06-26

申办/合作机构

Idorsia Pharmaceuticals Ltd.

100 项与 Aprocitentan 相关的临床结果

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100 项与 Aprocitentan 相关的转化医学

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100 项与 Aprocitentan 相关的专利（医药）

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项与 Aprocitentan 相关的文献（医药）

2025-04-01·ANNALS OF PHARMACOTHERAPY

Pressing Update: Aprocitentan for the Treatment of Hypertension

Review

作者: Whitner, Chardae ; Vascimini, Angelina ; St. Onge, Erin ; Huston, Jessica ; Phillips, Bradley

Objective::

This article reviews the published data including the pharmacology, efficacy, and safety of aprocitentan, a novel endothelin receptor antagonist developed to treat hypertension in conjunction with additional agents.

Data sources::

A literature search was conducted from drug discovery until May 2024 through PubMed, MEDLINE, and National Institutes of Health Clinical Trials Registry utilizing the following search terms: Tryvio, aprocitentan, hypertension, resistant hypertension, endothelin receptor antagonist, and ACT-132577.

Study selection and data extraction::

All relevant English-language studies, or studies that could be appropriately translated into English, containing the pharmacology, pharmacokinetics, safety, and efficacy of aprocitentan, were selected for review.

Data synthesis::

In the setting of resistant hypertension, aprocitentan has shown significant reductions in blood pressure in both medical office and 24-hour ambulatory settings at 4 weeks with a sustained effect at 40 weeks. Studies evaluating cardiovascular risk reduction have not been conducted at this time. Fluid retention and edema were the most frequent adverse events reported in clinical studies with aprocitentan. As a class, endothelin receptor antagonists may cause fetal harm; aprocitentan should be used with caution to avoid embryo-fetal toxicity.

Relevance to patient care and clinical practice in comparison to existing drugs::

Owing to the existent barriers for the treatment of resistant hypertension, aprocitentan presents itself as an effective option when added to traditional antihypertensives. This single-strength, once-daily regimen may serve as an appealing option to both patients and prescribers.

Conclusion::

Aprocitentan is a safe and effective medication for the treatment of hypertension when added to other pharmacological therapies.

2025-04-01·HYPERTENSION

Aprocitentan for Blood Pressure Reduction in Black Patients

Article

作者: Andrawis, Nabil S. ; Danaietash, Parisa ; Scott, David ; Schlaich, Markus P. ; Sassi-Sayadi, Mouna ; Clozel, Martine ; Dreier, Roland F. ; Wang, Ji-Guang ; Ferdinand, Keith C. ; Weber, Michael A. ; Narkiewicz, Krzysztof ; Gabra, Nashwa ; Flack, John M.

BACKGROUND::

Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).

METHODS::

Patients with confirmed resistant hypertension were randomized to aprocitentan 12.5 mg, 25 mg, or placebo for 4 weeks (part 1). They subsequently received aprocitentan 25 mg for 32 weeks (part 2) before re-randomization to aprocitentan 25 mg or placebo (part 3).

RESULTS::

Eighty-two patients randomized in the PRECISION study were Black individuals. At week 4, aprocitentan 12.5 and 25 mg reduced office trough systolic BP (−11.3 and −11.9 mm Hg) to a similar degree as placebo (−12.0 mm Hg). Using 24-hour ambulatory BP monitoring, the placebo effect was minimal (−0.7 mm Hg), and aprocitentan reduced systolic BP by 4.0 and 8.6 mm Hg. During part 2, office BP continued to decrease (−16.4 mm Hg at week 36). In part 3, office and ambulatory systolic BP increased on placebo (+9.9 and +8.1 mm Hg, respectively), whereas the BP-lowering effect was maintained with aprocitentan. Aprocitentan markedly reduced albuminuria during the study. The most frequent adverse event was peripheral edema, occurring in 3 patients (10%) receiving aprocitentan 25 mg versus none receiving aprocitentan 12.5 mg or placebo.

CONCLUSIONS::

Aprocitentan reduced BP and albuminuria in Black individuals with resistant hypertension. The BP-lowering efficacy was similar to that of the overall PRECISION population. Aprocitentan may represent an important addition to the often difficult-to-control hypertension in Black individuals.

REGISTRATION::

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03541174.

2025-03-01·Nature Reviews Nephrology

Endothelin receptor antagonists in chronic kidney disease

Review

作者: Kohan, Donald E ; Liew, Adrian ; Dhaun, Neeraj ; Smeijer, J David ; Noronha, Irene L ; Heerspink, Hiddo J L

Endothelin-1 is a potent vasoconstrictor that has diverse physiological functions in the kidney, including in the regulation of blood flow and glomerular filtration, electrolyte homeostasis and endothelial function. Overexpression of endothelin-1 contributes to the pathophysiology of both diabetic and non-diabetic chronic kidney disease (CKD). Selective endothelin receptor antagonists (ERAs) that target the endothelin A (ET_A) receptor have demonstrated benefits in animal models of kidney disease and in clinical trials. In patients with type 2 diabetes and CKD, the selective ET_A ERA, atrasentan, reduced albuminuria and kidney function decline. Concerns about the increased risks of fluid retention and heart failure with ERA use have led to the design of further trials to optimize dosing and patient selection. More recent studies have shown that the dual ET_A receptor and angiotensin receptor blocker, sparsentan, preserved kidney function with minimal fluid retention in patients with IgA nephropathy. Moreover, combined administration of a low dose of the ET_A-selective ERA, zibotentan, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, enhanced albuminuria reduction and mitigated fluid retention in patients with CKD. Notably, sparsentan and aprocitentan have received FDA approval for the treatment of IgA nephropathy and treatment-resistant hypertension, respectively. This Review describes our current understanding of the use of ERAs in patients with CKD to guide their optimal safe and effective use in clinical practice.

119

项与 Aprocitentan 相关的新闻（医药）

2025-03-17

·GlobeNewswire-Health Care

US FDA removes REMS requirement for TRYVIO (aprocitentan) – minimizing the burden on the healthcare delivery systems and patients

Ad hoc announcement pursuant to Art. 53 LR FDA confirms that prescribers and pharmacists are no longer expected to interact with the REMS Allschwil, Switzerland – March 17, 2025Idorsia Ltd (SIX: IDIA) today announced that – effective immediately – the US FDA has fully released TRYVIO™ (aprocitentan) from its REMS (Risk Evaluation and Mitigation Strategy) requirement. TRYVIO is Idorsia’s dual endothelin receptor antagonist (ERA) indicated for the treatment of systemic hypertension in combination with other antihypertensives to lower blood pressure in patients who are not adequately controlled on other drugs. The US FDA has determined that a REMS is no longer necessary to ensure the benefits of TRYVIO outweigh the risk of embryo-fetal toxicity and that labeling is sufficient for conveying the safety information. The FDA have therefore removed the requirement to minimize the burden on the healthcare delivery system of complying with the REMS. Consequently, Idorsia is also released from the post marketing requirement (PMR) to conduct a worldwide descriptive study that collects prospective and retrospective data in women exposed to TRYVIO during pregnancy and/or lactation as these data are no longer needed. Idorsia no longer has post marketing requirements for TRYVIO. Martine Clozel, Chief Scientific Officer of Idorsia, commented:“As a dual endothelin receptor antagonist (ERA), TRYVIO targets a previously unaddressed but important pathway in systemic hypertension, the endothelin pathway. The FDA decision that a REMS is no longer necessary for TRYVIO reflects the progressive understanding of the risk / benefit of TRYVIO. The decision of the FDA is based on an evaluation of human fetal outcomes after exposure to a drug in the ERA class. This change is very important considering that TRYVIO can be prescribed to a large patient population, who have a high cardiovascular risk and whose hypertension could not be brought under control with the previous classes of medication. This comes on top of the outstanding properties of TRYVIO, the result of over 25 years of optimization in our drug discovery team.” Michael Moye, President and General Manager of Idorsia US, commented:“TRYVIO is the first new antihypertensive working via a new pathway for over 40 years. It is a once-daily tablet, is easy to use for patients and easy to prescribe for physicians. In the absence of clinically relevant drug interactions, it can be safely combined with complex drug regimens and, importantly, can be used by chronic renal failure patients with hypertension without dose modification. On top of existing antihypertensives, aprocitentan has been shown to decrease systolic blood pressure by more than 15 mmHg from baseline at trough, and it is well tolerated over the long term. The release of the REMS is fantastic news as it makes TRYVIO even easier to prescribe. TRYVIO is available to prescribe today, and we are now looking for the best commercial solution to fully launch this important medication that fills a large unmet patient need.” Idorsia will submit revised labeling to the US FDA in accordance with the release of the REMS in the coming weeks. For current information on TRYVIO see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). TRYVIO continues to be commercially available through Walgreens Specialty Pharmacy. For more information visit the following websites: US Healthcare Professionals: www.TRYVIOhcp.com US Patients: www.TRYVIO.com Notes to the editor About aprocitentanAprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ETA and ETB receptors. Aprocitentan is approved as TRYVIO™ in the US for the treatment of systemic hypertension in combination with other antihypertensives and has been commercially available since October 2024. Aprocitentan is approved as JERAYGO™ for the treatment of resistant hypertension in combination with other antihypertensives in the European Union and the UK and marketing authorization applications are under review in Canada, and Switzerland. About IdorsiaIdorsia Ltd is reaching out for more – we have more passion for science, we see more opportunities, and we want to help more patients. The purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve Idorsia into a leading biopharmaceutical company, with a strong scientific core. Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA). For further information, please contactInvestor & Media RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.relations@idorsia.com – media.relations@idorsia.com – www.idorsia.com The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Attachment Press Release PDF

上市批准

2025-03-12

·抗体圈

难成药蓝海，重磅炸弹+1

心血管领域有望再迎来一个重磅炸弹。 3月11日，Mineralys Therapeutics宣布Lorundrostat治疗不受控制或耐药性高血压的关键性3期临床Launch-HTN和关键性2期临床Advance-HTN均达到主要临床终点。 Lorundrostat是一款口服、高选择性醛固酮合成酶（ALDOS）抑制剂，主要定位于高血压患者的三、四线治疗，即未控制、耐药性的难治性高血压人群。众所周知，高血压是导致心血管疾病的重要危险因素之一，而长期无法良好控制的高血压人群显然是更高危的人群，Lorundrostat的成药不仅为Mineralys打开了宽阔的市场，同时也给难治性高血压人群提供一个全新的治疗方案。 01 “小众”难治性高血压市场？全球高血压患者规模庞大，仅以中美两国为例，据《中国心血管健康与疾病报告2022》显示中国成人高血压患者约为2.45亿人，据美国心脏协会（AHA）数据显示2015-2018年期间国约有1.215亿成年人患有高血压。高血压的发生与多种因素相关，包括RAAS激活、肾脏排泄功能障碍、血管内皮损害、胰岛素抵抗和家族遗传等。目前，降血压药物种类较多，大致可以分为利尿剂、β受体阻滞剂、钙离子通道阻滞剂、血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体阻断剂等，其中沙坦类、钙离子通道阻滞剂是国内临床应用最广的降压药物。如何定义难治性高血压（RHTN）呢？2008年美国心脏学会认为：同时使用3种不同作用机制降压药物，血压仍在目标水平以上，需要4种或以上降压药物才能使血压达标者为难治性高血压。从治疗达标率角度看，WHO数据显示，2019年全球高血压控制率21%，中国高血压控制率16%；据AHA数据，美国成人高血压控制率22.5%。数据维度来说，全球有近80%患者血压未得到有效控制控制，其中又可分为假性难治性高血压和难治性高血压。根据AHA统计，美国1.2亿高血压患者，RHTN比例为10%；建投医药数据显示，2023年中国RHTN患者约4800万人，占高血压患者总数的15%；如此看来，RHTN创新治疗药物潜在市场空间巨大。高血压难以控制与多种因素有关，一般高血压起始治疗采用两联药物治疗，根据能否控制达标进行三联、四联的加码，但因为降压药本身有一定副作用（有研究表明副作用是30%高血压患者药物不依从原因），加上数联药物治疗患者依从性有所降低；另外，RHTN也与RAAS失调、遗传等因素相关。这里就不得不提肾素-血管紧张素-醛固酮系统（RAAS），RAAS被激活时血管紧张素原（AGT）裂解生成血管紧张素I（Ang I），随后Ang I会在血管紧张素转换酶（ACE）转化为生血管紧张素II（Ang II），Ang II是一种血管收缩剂，它刺激醛固酮从肾上腺释放，醛固酮促进肾脏中的钠和水潴留，导致血容量和血压增加。前文提到Lorundrostat便可以高选择抑制醛固酮，从而达到为RHTN患者控制血压的目的。另外，一项美国的研究显示：在慢性肾脏病伴高血压的患者中表观难治性高血压的比例更高，可达30%以上。 02 Lorundrostat成色几何？前面提到了Mineralys Therapeutics的ALDOS抑制剂Lorundrostat的相关作用机制和对应市场，接下来我们从两大临床Launch-HTN、Advance-HTN分析药物的疗效。 Launch-HTN研究入组了1083位难治性和控制不良的高血压患者，旨在探索Lorundrostat与2-5种现有高血压药物联合治疗的疗效和安全性，主要终点为第6周自动化诊室血压测量（AOBP）收缩血压与基线的变化。（AOBP指患者在独立空间安静接受自动化电子血压测量仪自动测量3～5次血压，自动求取血压平均值）受试者随机分配到三个组，分别是安慰剂组、Lorundrostat 50mg每日一次组、Lorundrostat 50mg每日一次且据需要在第6周调整至100mg每日一次组。临床结果显示，第6周时50mg组的收缩压绝对降低值为16.9mmHg，经安慰剂调整后的降低值为9.1mmHg（p<0.0001）；第12周时50mg组的收缩压绝对降低值为19.0mmHg，经安慰剂调整后的降低值为11.7mmHg（p<0.0001）。安全性方面，Lorundrostat表现相当出色。50mg组、50至100mg组严重不良事件（SAEs）发生率分别为0.7%和2.4%，导致停药的治疗相关不良事件（TEAEs）发生率分别为1.5%和2.6%，安慰剂组SAEs、TEAEs发生率分别为3.3%、1.9%。此外，大家关注的高钾血症（血清钾>6.0 mmol/L）的发生率在50mg组和50至100mg组分别为1.1%和1.5%。 Advance-HTN这项关键二期更像是为Lorundrostat验证疗效排除干扰性的因素，其设置了一个优化治疗背景：采用两种降压药物治疗患者以及3-5种降压药患者在入组筛选前需要停用现有药物并采取标准治疗方案治疗（具体可详见前文欧洲高血压联合用药流程图），入组患者分别分配到安慰机组、Lorundrostat 50mg每日一次组、Lorundrostat 50mg每日一次并在第4周可根据预定义标准调整至100mg组。该研究的主要终点为24小时动态血压监测（ABPM）评估的收缩压变化，治疗12周后相比安慰剂的平均降低值。初步的临床结果显示，在第12周时50mg组的安慰剂调整后收缩压降低值为7.9mmHg，具有高度统计学意义，其他预先设定的终点指标与Launch-HTN研究中观察到的结果一致；并且Lorundrostat治疗组具备良好安全性与耐受性，50mg组和50至100mg组高钾血症的发生率在分别为5.3%和7.4%。 Lorundrostat这两项关键临床，足以证明其在未控制、难治性高血压患者带来极高的临床益处，显然其将成为三线、四线高血压患者的治疗选择，按Mineralys公司口径其辐射的患者至少在2000万人。另外，Lorundrostat除了未控制或难治性高血压适应症，Mineralys还在探索其在慢性肾病（CKD）和阻塞性睡眠呼吸暂停综合征（OSA），其中CKD的顶线数据将在2025年二季度公布，早前同靶点药物BI 690517已经验证可显著降低CKD患者蛋白尿且转化为肾脏保护功能的效果，这也让市场投资者对Lorundrostat的CKD验证性数据有着非常大期待。对于Lorundrostat的销售潜力，瑞银预计其耐药性高血压领域的峰值有望达到20亿美元。 03 赛道争霸：阿斯利康、Idorsia还是Alnylam？盯着这块“肥美”市场的公司不在少数。 Lorundrostat公布顶线结果后，投资者将视角转向同属于醛固酮合成酶抑制剂阿斯利康的Baxdrostat，其将在2025H2公布三期临床的最终结果。同为醛固酮合成酶抑制剂，Lorundrostat与Baxdrostat差异重点大概在对靶点的选择性和半衰期层面，体外试验中对ALDOS的选择性分别是皮质醇合成酶的374倍和>100倍，两者半衰期则分别为10-12小时、25-31小时。从Baxdrostat疗效数据来看，针对难治性高血压患者的二期BrigHTN研究中，接受2mg治疗的患者经安慰剂调整后降低11.0mmHg的诊室收缩压（SBP）。非头对头数据比较下，Baxdrostat与Lorundrostat降压效果看起来相近，不过Baxdrostat二期样本量较小（ 2mg组患者67人），未来仍需考察其三期临床数据含量。阿斯利康对于Baxdrostat未来商业化前景寄予厚望，据公司估算美国和欧洲五国共有3700万难治性高血压患者病情未得到有效控制，叠加慢性肾病相关高血压和原发性醛固酮增多症等适应症，公司预计Baxdrostat年销售峰值超过50亿美元。 Lorundrostat另一同适应症竞争对手则是瑞士药企Idorsia的Aprocitentan，Aprocitentan是一款双内皮素受体拮抗剂，2024年获FDA批准用于难治性高血压，通过双重阻断内皮素受体降低血压。在一项730名难治性高血压患者临床三期中，在第4周时Aprocitentan 12.5 mg、Aprocitentan 25 mg组与安慰剂组的差异分别为-3.8mmHg 和-3.7mmHg。我们看到，Aprocitentan的降血压疗效在在研药物横向非头对头数据对比下显然疗效稍显不足，但其依旧获得了FDA的批准。 Lorundrostat最大的竞争对手，大概率是Alnylam的靶向血管紧张素原（AGT）的RNAi疗法Zilebesiran。从机制上看，其可以在上游就抑制肝脏中AGT的合成，导致AGT蛋白的持续减少，最终导致具有血管收缩作用的血管紧张素II水平持续下降‌。 Zilebesiran在轻中度高血压二期临床KARDIA-2已经获得成功，其作为标准治疗的附加疗法，与抗高血压药物联用可额外降低高达1mmHg的24小时平均收缩压；另外，Alnylam也启动了KARDIA-3研究，评估Zilebesiran在2-4种降压治疗仍血压控制欠佳且合并心血管高危因素或进展性慢性肾脏病的高血压患者中的疗效。不过，未来Zilebesiran也有可能作为Lorundrostat联用的“差异化组合”，期待日后的药物竞争格局的演变。结语：纵观难治性高血压的已商业化、后期临床创新管线，不仅可以发现这个领域存在较大的未满足临床需求，同时未来几年内马上会有更佳效果和安全性的迭代药物即将上市，这显然会打开赛道的市场空间。从中短期的进度来看，Lorundrostat的三期成功使得Mineralys在与阿斯利康的竞争中占得先机，同时我们也看好未来其获批在欧美的放量进程，更期待有国产创新药物加入战团。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

AHA会议临床结果临床2期临床1期临床3期

2025-03-10

·Endpoints

Mineralys’ Phase 3 blood pressure pill data support potential FDA approval

Topline pivotal data suggest that Mineralys Therapeutics’ experimental hypertension pill is a good prospect not only for approval but also for widespread adoption as a treatment for patients whose condition has not responded to other drugs. The company’s stock $MLYS rose 52% in early trading. The Phase 3 Launch-HTN trial signed up over 1,000 adults whose high blood pressure was uncontrolled despite taking two to five background antihypertensive medications. Two doses of Mineralys’ lorundrostat were tested: One group received the aldosterone synthase inhibitor at 50 mg once daily, and another group at a 50 mg-daily dose titrated up to 100 mg per day, as needed, at week six. After six weeks, pooled data from patients in both lorundrostat arms showed a blood pressure reduction of 9.1 mmHg more than those with a placebo (p<0.0001), the company said Monday. After a further six weeks, the placebo-adjusted blood pressure drop in the 50 mg-only group had deepened to 11.7 mmHg, which was also significant. However, patients who had their doses titrated up to 100 mg per day had a lesser blood pressure reduction at the 12-week point — just 8.4 mmHg on a placebo-adjusted basis (p<0.0016). Mineralys also said that “equivalent” systolic blood pressure cuts were seen in subjects with uncontrolled hypertension, who were on two antihypertensive medications, and in those with resistant hypertension, who were taking three to five drugs. Treatment emergent serious adverse events (SAEs) were seen in 2.2% of patients in the 50 mg and 0.7% in the 50 mg with optional escalation to 100 mg arms, respectively, Mineralys said, versus 3% with placebo. One subject in the 50 mg arm had an SAE that was related to lorundrostat. The 9.1 mmHg benefit over placebo on the primary endpoint meets Stifel analysts’ “upside” case. In a Feb. 24 note, the analysts wrote that a benefit of between 8 and 10 mmHg would not only be approvable, but should secure broad insurance coverage for lorundrostat as a fourth-line hypertension therapy. Lorundrostat appears to be a better prospect than the last drug approved for resistant hypertension. Idorsia’s endothelin receptor antagonist Tryvio reached the US a year ago on the strength of a 3.8 mmHg reduction. But this was seen with the lower dose in its pivotal trial; the higher dose was not approved because of safety concerns. Tryvio’s label carries a black box warning of embryo-fetal toxicity. Idorsia’s efforts to sign up a partner for Tryvio fell through last month, leaving the company in a difficult financial position. Mineralys also released data from a Phase 2 study called Advance-HTN in patients taking an optimized background treatment of two or three antihypertensive drugs. This study also hit its primary endpoint, yielding a placebo-adjusted reduction in systolic BP of 7.9 mmHg at three months with a 50 mg dose of lorundrostat. Blood pressure was measured slightly differently here, using a 24-hour average, whereas Phase 3 patients’ blood pressure was measured in their doctors’ offices. Office blood pressure measurements tend to be slightly higher than ambulatory measurements because of the so-called white coat syndrome . The company said that efficacy in the dose-escalation cohort and safety and tolerability data “mirrored the pattern” seen in Launch-HTN. Further data from Advance-HTN will be presented on March 29 at the American College of Cardiology’s annual meeting. Editor’s note: This article has been updated with Mineralys’ the latest stock move.

临床结果临床3期临床2期

100 项与 Aprocitentan 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11441	-	-	DB15059

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
难治性高血压	欧盟	Idorsia Ltd.	2024-07-01
难治性高血压	冰岛	Idorsia Ltd.	2024-07-01
难治性高血压	列支敦士登	Idorsia Ltd.	2024-07-01
难治性高血压	挪威	Idorsia Ltd.	2024-07-01
高血压	美国	Idorsia Pharmaceuticals Ltd.	2024-03-19

未上市

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
原发性高血压	申请上市	加拿大	Idorsia Pharmaceuticals Ltd.	2025-01-01
慢性肾病	临床3期	-	Idorsia Pharmaceuticals Ltd.	2020-01-01
慢性肾病	临床3期	-	Janssen Biotech, Inc.	2020-01-01
肝硬化	临床1期	德国	Idorsia Pharmaceuticals Ltd.	2020-06-26
肝硬化	临床1期	波兰	Idorsia Pharmaceuticals Ltd.	2020-06-26
肝损伤	临床1期	德国	Idorsia Pharmaceuticals Ltd.	2020-06-26
肝损伤	临床1期	波兰	Idorsia Pharmaceuticals Ltd.	2020-06-26
肾功能不全	临床1期	捷克	Idorsia Pharmaceuticals Ltd.	2017-06-03

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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


NCT03541174 (PRECISION, Pubmed \| Hypertension)	临床3期	低血压	-	Aprocitentan 12.5 mg	構範齋淵顧窪觸餘艱壓(襯鬱範壓蓋淵壓願憲繭) = 窪鏇範鏇壓糧襯鑰膚網鑰蓋構願簾觸觸鏇艱遞 (襯顧觸築鑰醖範遞網廠 )	积极	2025-04-01
				Aprocitentan 25 mg	構範齋淵顧窪觸餘艱壓(襯鬱範壓蓋淵壓願憲繭) = 獵願淵築簾鏇選獵餘鹽鑰蓋構願簾觸觸鏇艱遞 (襯顧觸築鑰醖範遞網廠 )
PRECISION (ESH2024)	临床3期	难治性高血压	-	Aprocitentan 12.5 mg	衊憲繭選鑰鹹鬱鬱簾選(構淵齋製蓋醖選淵繭憲) = 艱顧壓憲鑰艱鹹鑰廠願築繭襯鏇餘窪醖餘繭醖 (顧窪網夢淵遞範鏇構網 )	积极	2024-05-01
				Aprocitentan 25 mg	衊憲繭選鑰鹹鬱鬱簾選(構淵齋製蓋醖選淵繭憲) = 鏇淵觸築觸廠範廠醖遞築繭襯鏇餘窪醖餘繭醖 (顧窪網夢淵遞範鏇構網 ) 更多
PRECISION (ESH2024)	临床3期	难治性高血压	93	Aprocitentan 12.5 mg	獵夢鹽選願壓選簾鹽餘(鏇廠範糧網範膚製蓋窪) = 壓願製範顧鹽齋淵襯積選夢選餘積簾鑰餘廠淵 (選廠積廠繭顧窪廠襯夢 ) 更多	积极	2024-05-01
				Aprocitentan 25 mg	獵夢鹽選願壓選簾鹽餘(鏇廠範糧網範膚製蓋窪) = 蓋範鑰膚艱膚獵鏇遞鏇選夢選餘積簾鑰餘廠淵 (選廠積廠繭顧窪廠襯夢 ) 更多
NCT03541174 (FDA) 人工标引	临床3期	高血压	-	Aprocitentan (12.5 mg)	壓網糧鬱艱範積壓廠遞(網顧範餘襯膚糧遞夢壓) = 蓋艱鹽襯衊餘鹽願繭願選鹹遞蓋顧膚簾鏇蓋窪 (壓壓夢齋齋願繭積廠構, −17.5 ~ −13.3) 更多	优效	2024-03-19
				Placebo	壓網糧鬱艱範積壓廠遞(網顧範餘襯膚糧遞夢壓) = 築鏇鏇鹽夢夢範網築選選鹹遞蓋顧膚簾鏇蓋窪 (壓壓夢齋齋願繭積廠構, −13.7 ~ −9.5) 更多
PRECISION (ESH2023)	临床3期	难治性高血压	730	Aprocitentan 12.5 mg	餘網觸鹽齋觸鏇衊願繭(積鹽顧夢簾觸襯積顧選) = 繭夢積鑰膚製醖網鏇憲鏇簾築餘選淵齋鬱蓋獵 (網窪構糧積鬱顧網壓積 )	积极	2023-06-01
				Aprocitentan 25 mg	餘網觸鹽齋觸鏇衊願繭(積鹽顧夢簾觸襯積顧選) = 鏇觸醖醖廠網鹹糧憲襯鏇簾築餘選淵齋鬱蓋獵 (網窪構糧積鬱顧網壓積 )
NCT03541174 (PRECISION, CTgov)	临床3期	难治性高血压	730	Aprocitentan 12.5 mg (Aprocitentan 12.5 mg in Part 1 (Double-blind))	醖衊齋艱醖築築廠艱鹹(膚選繭鬱遞顧顧齋窪簾) = 鑰獵範餘範選鹽鹹範選廠鏇製構憲選範憲構鏇 (顧構壓簾鹽膚夢窪淵顧, 膚構醖鹹窪鏇遞鏇選遞 ~ 襯鏇觸築淵蓋鹹遞製夢) 更多	-	2023-03-21
				Aprocitentan 25 mg (Aprocitentan 25 mg in Part 1 (Double-blind))	醖衊齋艱醖築築廠艱鹹(膚選繭鬱遞顧顧齋窪簾) = 鏇糧廠鏇膚顧鬱選築製廠鏇製構憲選範憲構鏇 (顧構壓簾鹽膚夢窪淵顧, 糧範廠獵觸鹽願網構選 ~ 窪構觸簾窪顧觸觸醖鏇) 更多
NCT02603809 (CTgov)	临床2期	原发性高血压	1,659	Placebo (Placebo)	膚廠製壓築顧醖蓋壓築(襯選築窪構觸鬱憲膚構) = 範艱廠簾鬱壓壓壓簾窪鏇願糧鹽觸選衊蓋築遞 (構膚獵鑰壓積遞齋獵壓, 5.4) 更多	-	2020-04-13
				Aprocitentan 5 mg (Aprocitentan 5 mg)	膚廠製壓築顧醖蓋壓築(襯選築窪構觸鬱憲膚構) = 鹹觸糧齋鏇壓襯齋鹽簾鏇願糧鹽觸選衊蓋築遞 (構膚獵鑰壓積遞齋獵壓, 5.5) 更多
NCT02603809 (ESC2019)	临床2期	高血压	490	Aprocitentan 5 mg	糧窪鬱積蓋選鑰構製願(構鹽醖壓繭簾鹹壓衊糧) = 製齋鬱廠蓋衊網襯獵夢襯鏇蓋鹹餘積憲鹹蓋積 (構願壓遞衊繭網鬱鏇獵 ) 更多	-	2019-08-31
				Aprocitentan 10 mg	糧窪鬱積蓋選鑰構製願(構鹽醖壓繭簾鹹壓衊糧) = 範壓齋選鹽範網鏇壓衊襯鏇蓋鹹餘積憲鹹蓋積 (構願壓遞衊繭網鬱鏇獵 ) 更多