Tryvio (aprocitentan) / Idorsia - LARVOL DELTA

Current Knowledge About Aprocitentan in Hypertension. (PubMed, Int J Mol Sci) - "Moreover, ACT was compatible with other antihypertensive agents, demonstrating synergistic or additive effects in some cases. Since HT is frequently associated with comorbidities and ACT targets a different pathway than the existing antihypertensive drugs, ACT may play a pivotal role in the management of resistant hypertension."

Journal • Review • Cardiovascular • Genetic Disorders • Hypertension • Obesity

Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension. (PubMed, Hypertension) - P3 | "Aprocitentan may confer considerable cardiovascular and kidney-protective benefits in these difficult-to-treat patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

The antihypertensive agent ACT-132577 alleviates cuproptosis and pressure-overload-induced vascular remodelling by modulation of the NEDD4-LCTR1-copper signaling. (PubMed, FEBS J) - "More importantly, knocking down NEDD4L significantly abolished the effects of ACT-132577 on cuproptosis and VSMC phenotypic transition. In conclusion, ACT-132577 plays a crucial role in cuproptosis and aortic remodelling by modulation of the NEDD4L-CTR1-copper signaling, providing a novel perspective on its therapeutic potential in mitigating pressure overload-induced vascular remodelling."

Journal • Cardiovascular • Hypertension • Targeted Protein Degradation • ACTA2 • DLAT • MMP2 • MMP9 • NEDD4 • PDGFB • UBR5

The use of predictive, preventive, and personalized medical approaches to optimize hypertension management. (PubMed, EPMA J) - "The 3PM framework leverages AI-driven integration of multi-omics, retinal imaging like ViT models, and hemodynamic profiling for risk prediction and treatment response forecasting; genetic profiling such as MTHFR, UMOD variants, urinary proteomics (CKD273 classifier), and microbiome-guided nutrition for early intervention; and pharmacogenomics, digital phenotyping like smartphone-guided dosing, and novel therapies such as aprocitentan and finerenone for personalized efficacy. Specific findings include aprocitentan reducing systolic BP by -15.3 mmHg in resistant hypertension, UMOD-guided torasemide use lowering BP by 8.5 mmHg in carriers, and microbiome-based nutrition reducing systolic BP by 14% in hyperglycemic patients...3PM transforms hypertension management by enabling proactive, individualized care. However, rigorous validation, affordable diagnostics, pragmatic trials, and equitable access are essential to bridge translational gaps and..."

Journal • Review • Cardiovascular • Diabetes • Hypertension • MTHFR

Aprocitentan in Resistant Hypertension: Mechanistic Insights, Clinical Evidence, and Future Directions. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "Aprocitentan could potentially prove useful in the future for vascular disease, heart failure, and diabetic nephropathy. Clarifying its potential role in the future to treat hypertension and cardiorenal disease will only be discernible through longer-term trials on cardiovascular endpoints and cost-effectiveness."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hypertension • Hypotension • Metabolic Disorders • Nephrology • Renal Disease

Is Aprocitentan's Effect on Albuminuria Merely Due to Lowered BP? Subgroup Analysis of the PRECISION Trial (KIDNEY WEEK 2025) - P3 | "The low correlation between change in SiSBP and change in UACR suggests that APRO’s effect on UACR is at least partly independent of its effect on blood pressure. Table: Placebo-corrected changes in SiSBP and UACR (baseline to Week 4) with aprocitentan 12.5 mg and 25 mg in subgroups with renal impairment"

Cardiovascular • Chronic Kidney Disease • Hypertension • Renal Disease

Which Veterans Cannot Resist Aprocitentan? (KIDNEY WEEK 2025) - "Aprocitentan is currently non-formulary at the VA, but these data suggest a significant proportion of veterans with hypertension would be candidates to have it prescribed. Eligibility criteria for Aprocitentan"

Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Effects of aprocitentan on prognostically relevant ambulatory blood pressure-derived variables in resistant hypertension. (PubMed, J Hypertens) - "In addition to a significant and sustained day and night-time ambulatory BP reduction, aprocitentan was associated with a higher proportion of patients experiencing dipping pattern normalization and more pronounced BP load reduction, indicating prognostic relevance. Increased arterial stiffness or salt sensitivity did not alter the BP response to aprocitentan, suggesting additional clinical benefit."

Journal • Cardiovascular • Hypertension

Clinical Evaluation of QTc Interval Prolongation With the Dual Endothelin Receptor Antagonist Aprocitentan. (PubMed, J Cardiovasc Pharmacol Ther) - "The predicted upper bound of the 2-sided 90% ΔΔQTcF confidence interval exceeded the 10 ms threshold of regulatory concern at 16.10 µg/mL, which was close to the geometric mean maximum concentration (ie, 16.77 µg/mL) obtained with a 100 mg supratherapeutic dose.ConclusionsAt the highest therapeutic dose of 25 mg, there was no clinically significant prolongation of QTc. The risk of QT prolongation with therapeutic doses of aprocitentan is considered low."

Clinical • Journal • Cardiovascular • Hypertension • Hypotension

In brief: Embryotoxicity REMS removal for endothelin receptor antagonists. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Unveiling the Carbonic Anhydrase Inhibitory Profile of Aprocitentan: Kinetic and Structural Characterization. (PubMed, ACS Med Chem Lett) - "These findings highlight a previously unrecognized dual mechanism of action for aprocitentan involving not only endothelin receptor antagonism but also CA inhibition. The combined effect may enhance its antihypertensive efficacy and suggests new avenues for therapeutic exploration in resistant hypertension."

Journal • Cardiovascular • Hypertension

Aprocitentan: a new horizon in the treatment of hypertension. (PubMed, Expert Opin Pharmacother) - "However, a lack of long-term data necessitates future investigation regarding safety. Aprocitentan may represent a novel therapeutic alternative to treat patients with RH and CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Structure-Property Relationships Reported for the New Drugs Approved in 2024. (PubMed, Mini Rev Med Chem) - "The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structureproperty relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution."

Journal

Aprocitentan: The First Endothelin Receptor Antagonist for Resistant Hypertension. (PubMed, Am J Ther) - "Aprocitentan is a novel endothelin receptor antagonist approved for the treatment of resistant hypertension. It is a welcome development in the arsenal to fight against resistant hypertension for those with difficulty to manage with conventionally available antihypertensive medications."

Clinical • Journal • Cardiovascular • Hypertension • UGT1A1

Endothelin antagonists for hypertension: has their time finally arrived? (PubMed, Clin Sci (Lond)) - "Following a successful trial in resistant hypertension, a novel antihypertensive agent has been approved in Europe and in the U.S.A.: the dual ETAR/ETBR antagonist aprocitentan, which was recently approved for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Thus, the time has finally arrived for ET antagonists in hypertension."

Journal • Review • Cardiovascular • Hypertension • Hypotension

Endothelin Receptor Antagonists for the Treatment of Hypertension: Recent Data from Clinical Trials and Implementation Approach. (PubMed, Curr Cardiol Rep) - "Aprocitentan was well tolerated and the risk of fluid retention can be mitigated by close clinical monitoring and titration of diuretic therapy. Aprocitentan presents a novel treatment option for resistant hypertension, with particular efficacy noted in patient cohorts who have historically been challenging to achieve blood pressure targets in."

Journal • Review • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease

Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo. (PubMed, Drug Des Devel Ther) - "The metabolite ACT-132577 exhibited substantial increases in t1/2, Tmax, and Cmax. Furthermore, molecular docking revealed that the metabolic inhibition of macitentan by imperatorin and curcumin occurred through binding to the site on CYP3A4. However, further investigation is necessary to ascertain whether this phenomenon will occur in humans."

Journal • Preclinical • CYP3A4

Idorsia announces financial results for the first quarter 2025 – QUVIVIQ taking off in Europe and TRYVIO REMS removal increases the value of this outstanding asset (GlobeNewswire) - "QUVIVIQ (daridorexant): Strong performance and accelerating sales in Q1 2025 with total Idorsia-led net sales of CHF 25 m; QUVIVIQ EUCAN: Demand grew by 50% from Q4 2024 to Q1 2025, strongly driven by reimbursed markets. Overall, more than 10 million nights of sleep prescribed in Q1 2025...QUVIVIQ net sales of around CHF 110 m....In March 2025, the US FDA fully released TRYVIO from its REMS (Risk Evaluation and Mitigation Strategy) requirement to minimize the burden on the healthcare delivery system of complying with the REMS. 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. As a result, a rapid transition from specialty pharmacy to a wide retail pharmacy distribution model is underway."

FDA event • Sales • Cardiovascular • Hypertension • Insomnia

Revolutionizing hypertension treatment: aprocitentan's dual action against resistant hypertension. (PubMed, Expert Rev Hematol) - No abstract available

Journal • Cardiovascular • Hypertension

Aprocitentan for Treatment-Resistant Hypertension: Pharmacology Concepts and Clinical Insights. (PubMed, J Cardiovasc Pharmacol) - "Animal study data from past endothelin receptor antagonists showed this class of agents may lead to birth defects and was the basis for aprocitentan's black-box warning. Overall, clinical trial data supports aprocitentan's use as an effective agent for the TRH, but clinicians will need to individualize patient treatment selection and consider the safest and most efficacious options currently available."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1

Aprocitentan in hypertension management: clinical efficacy, safety, and future prospects. (PubMed, Ann Med Surg (Lond)) - "However, Aprocitentan's use is associated with safety concerns, such as hepatotoxicity, fluid retention, and embryo-fetal toxicity, necessitating careful monitoring. Aprocitentan represents a significant advancement in HTN management, offering a new therapeutic option for patients with uncontrolled HTN, although vigilant monitoring and informed decision-making are essential to mitigate potential risks and ensure optimal outcomes."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatology • Hypertension • Renal Disease • EDN1

US FDA approves an updated label for TRYVIO (aprocitentan) removing the REMS requirement (GlobeNewswire) - "Idorsia Ltd...announced that the US Food & Drug Administration (FDA), after having released TRYVIO from its REMS (Risk Evaluation and Mitigation Strategy) requirement (announced on March 17, 2025), has now approved the updated label for TRYVIO (aprocitentan)...The FDA determined that a REMS was 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....As shown in the Phase 3 PRECISION study, TRYVIO decreased systolic blood pressure by more than 15 mmHg from baseline in patients with confirmed resistant hypertensive despite treatment with a combination of antihypertensives."

FDA approval • Hypertension

EFFECT OF APROCITENTAN ON BLOOD PRESSURE AND ALBUMINURIA IN PATIENTS WITH RESISTANT HYPERTENSION TREATED WITH SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT2I) - JI-Guang Wang (ACC 2025) - "This suggests aprocitentan was equally effective in lowering SBP irrespective of concomitant SGLT2i therapy, whereas a more pronounced effect on albuminuria reduction was observed in patients already receiving SGLT2i for diabetes. The limitations of this analysis include a low number of patients and lack of SGLT2i only group."

Clinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease

A Drug-drug Interaction Trial in Healthy Female Participants to Investigate the Effect of Aprocitentan on Combined Hormonal Contraceptives (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Idorsia Pharmaceuticals Ltd. | Not yet recruiting ➔ Completed

Trial completion

Idorsia announces financial results for 2024 (GlobeNewswire) - "QUVIVIQ (daridorexant): Outstanding launch dynamic in France, and a strong performance in Germany accelerate sales in 2024 – Total Idorsia-led net sales of CHF 61 million in 2024; TRYVIO (aprocitentan): Commercially available in the US since October 2024; JERAYGO (aprocitentan): Approved in European Union in June 2024 and the UK in January 2025 – marketing authorization application under review in Switzerland and Canada."

Commercial • Filing • Cardiovascular • Hypertension • Sleep Disorder