Tryvio (aprocitentan) / J&J, Idorsia - LARVOL DELTA

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

Idorsia reaches an agreement with significant bondholders to restructure its convertible bond debt and to secure funding for future operations (Idorsia Press Release) - "Agreement with Viatris to revise collaboration for selatogrel and cenerimod results in the removal of significant cash requirement for 2025...In a third step of the restructuring, a special purpose vehicle (SPV) will be created. Idorsia intends to transfer to this SPV its rights to selatogrel and cenerimod, and its rights to aprocitentan. A bond exchange offer will be launched by the SPV, where the CB2025 and CB2028 bondholders will be offered the opportunity to exchange their convertible bonds for newly created notes issued by the SPV (SPV Notes)....Any potential net payments for milestones and royalties from selatogrel and cenerimod, as well as any potential net proceeds from a deal for aprocitentan will be used to repay holders of the SPV Notes."

Commercial • Cardiovascular • Lupus

Aprocitentan mitigates doxorubicin-induced cardiotoxicity by inhibiting cuproptosis, oxidative stress, and mitochondrial impairments via the activation of sirtuin 7. (PubMed, Int Immunopharmacol) - "Moreover, aprocitentan administration strikingly reversed DOX-induced and elesclomol-aggravated cellular senescence and mitochondrial injury in cardiomyocytes. More importantly, knock-down of sirtuin 7 (SIRT7) by SIRT7 siRNA blocked the beneficial effects of aprocitentan on DOX-associated cuproptosis, oxidative stress, mitochondrial injury, and senescence in cardiomyocytes. In summary, aprocitentan exerts as a novel therapeutic agent for alleviation of DOX-induced cardiotoxicity through the inhibition of cuproptosis, oxidative stress, cardiac aging and mitochondrial injuries via the activation of SIRT7, offering new possibilities for prevention and treatment of DOX-induced cardiac disorders."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Oncology • CDKN1A • DLAT • EDN1 • SIRT7

Novel pharmacological approaches to lowering blood pressure and managing hypertension. (PubMed, Nat Rev Cardiol) - "Aprocitentan, a dual endothelin receptor antagonist, is the first agent from a novel class of antihypertensive drug to be licensed since 2007 and exemplifies innovative treatments on the horizon...We discuss the limitations of existing therapies and highlight promising new pharmacological approaches to hypertension management. Integrating these novel treatments alongside current pharmaceuticals combined with improved diagnostic and management strategies could substantially reduce the global burden of hypertension and associated cardiovascular disease."

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

A Game Changer for Resistant Hypertension: The Rise of Aprocitentan. (PubMed, J Cardiovasc Pharmacol) - "Indeed, the PRECISION clinical trial demonstrated aprocitentan's superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension."

Journal • Cardiovascular • Hypertension

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

New P1 trial

Efficacy and Safety of Aprocitentan in the Treatment of Hypertension: A Meta-Analysis of Evidence from Randomized Controlled Trials. (PubMed, Rev Cardiovasc Med) - "Aprocitentan significantly reduces blood pressure and has a good safety profile. However, it is worth noting that high doses of aprocitentan (50 mg) did not yield better blood pressure-lowering effects."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

Endothelin receptor antagonists (ERAs) can potentially be used as therapeutic drugs to reduce hypertension caused by small molecule tyrosine kinase inhibitors (TKIs). (PubMed, Front Pharmacol) - "Moreover, studies have demonstrated that ET plays a pivotal role in driving TKIs-induced hypertension. Therefore, this review aims to explore the significance of ET in the pathogenesis of hypertension induced by targeted anti-tumor drugs and investigate the potential therapeutic value of endothelin antagonists in managing hypertension caused by targeted anti-tumor drugs."

Journal • Review • Cardiovascular • Hypertension • Oncology

Aprocitentan for Blood Pressure Reduction in Black Patients. (PubMed, Hypertension) - P3 | "Aprocitentan may represent an important addition to the often difficult-to-control hypertension in Black individuals. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174."

Journal • Cardiovascular • Hypertension • Renal Disease

The Drug Update: Recent drug approvals, winter 2025 edition. (PubMed, Nurse Pract) - "In the first half of 2024, the US FDA approved several new drugs that have relevance for those practicing in primary care. This article, the winter 2025 edition of the journal's biannual Drug Update, highlights the following new medications: sotatercept-csrk (Winrevair), aprocitentan (Tryvio), resmetirom (Rezdiffra), berdazimer (Zelsuvmi), ceftobiprole medocaril sodium (Zevtera), sofpironium (Sofdra), and ensifentrine (Ohtuvayre)."

Journal

Novel pharmacologic approaches in resistant hypertension. (PubMed, Wiad Lek) - "Recently, valsartan/sacubitrol and flozins have been increasingly used in resistant hypertension, which have been introduced for the treatment of diseases other than hypertension but can be a supplement to previously used drugs in resistant hypertension...The results to date allow for the consideration of aprocitentan (a drug that inhibits endothelin receptors) or baxdrostat or another new aldosterone synthesis inhibitor in the treatment of resistant hypertension that does not respond to 4 drugs, including spironolactone. Further studies are needed to confirm the efficacy and safety of these new drugs in the treatment of resistant hypertension."

Journal • Review • Cardiovascular • Hypertension

Endothelin receptor antagonists in chronic kidney disease. (PubMed, Nat Rev Nephrol) - "In patients with type 2 diabetes and CKD, the selective ETA ERA, atrasentan, reduced albuminuria and kidney function decline...Moreover, combined administration of a low dose of the ETA-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."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Glomerulonephritis • Heart Failure • Hypertension • IgA Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • EDN1

Aprocitentan A Novel Dual Endothelin Receptor Antagonist for the Treatment of Resistant Hypertension (ASHP 2024) - No abstract available

Cardiovascular • Hypertension

The Pressure Is On for Resistant Hypertension The Use of Tryvio aprocitentan in Resistant Hypertension (ASHP 2024) - No abstract available

Cardiovascular • Hypertension

Blood pressure reduction in diabetic patients with resistant hypertension: results from the aprocitentan PRECISION study (AHA 2024) - "After ≥4 weeks of combination therapy (amlodipine/valsartan/hydrochlorothiazide), patients still hypertensive received single-blind placebo for a run-in period, followed by a 4-week double-blind part (APRO 12.5 mg, 25 mg, or placebo), a 32-week single-blind part (APRO 25 mg) and a 12-week double-blind withdrawal part (APRO 25 mg or placebo). APRO produced clinically relevant and sustained BP reduction in diabetic patients with RHT, consistent with the effect observed in the overall population."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Hypertension • Hypotension • Metabolic Disorders • Nephrology • Renal Disease

Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP (AHA 2024) - "Here we report the efficacy and safety of APRO in patients with increased NT-proBNP. 730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

A major effect of aprocitentan on albuminuria in patients with resistant hypertension (AHA 2024) - "In this analysis, we evaluated the effect of aprocitentan on UACR at both doses according to the baseline (BL) albuminuria (30-300 mg/g and >300mg/g). 730 patients with RHT on a standardized fixed-dose combination of amlodipine/ valsartan/hydrochlorothiazide were randomized to aprocitentan (12.5 mg or 25 mg) or placebo. Aprocitentan produced a major decrease of albuminuria regardless baseline level in patients with RHT. These finding support further research for aprocitentan in CKD patients"

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

Efficacy and safety of aprocitentan in patients with resistant hypertension receiving at least 4 antihypertensive medications including beta (β) blockers (AHA 2024) - "All were switched to a standardized fixed dose triple combination of amlodipine/valsartan/hydrochlorothiazide; and the 456 patients (62.5% of the 730 total) who were on β-blockers at screening continued throughout the study as well. In both subgroups, most events occurred during the first 8 weeks of treatment. The incidence of edema/fluid retention with aprocitentan was comparable with that of the placebo group in both subgroups thereafter.ConclusionsAprocitentan is effective in lowering BP and has a good safety and tolerability profile in patients with resistant hypertension who are taking 4 or more antihypertensive drugs including β-blockers."

Clinical • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hypertension