endothelin 1

TRYVIO (aprocitentan) in the US and JERAYGO in Europe present significant market potential as novel therapies for patients with hypertension inadequately controlled by existing treatments. TRYVIO, approved by the FDA in March 2024 and commercially available since October 2024, targets systemic hypertension in adults not adequately controlled on other drugs. LAS VEGAS, April 17, 2025 /PRNewswire/ -- DelveInsight's " TRYVIO/JERAYGO Market Size, Forecast, and Market Insight Report" highlights the details around TRYVIO/JERAYGO, a dual endothelin receptor antagonist. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TRYVIO/JERAYGO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Idorsia Pharmaceuticals' TRYVIO/JERAYGO (aprocitentan) Overview TRYVIO is a once-daily oral medication that acts as a dual endothelin receptor antagonist, blocking the binding of endothelin-1 (ET-1) to both ETA and ETB receptors. This mechanism makes it particularly effective for reducing blood pressure in adults whose hypertension remains uncontrolled with other treatments. TRYVIO also has a low risk of drug-drug interactions. The active ingredient, aprocitentan, is marketed as TRYVIO in the United States, while in the European Union and the UK, it is available under the brand name JERAYGO. Marketing applications are currently under review in Canada and Switzerland. Notably, TRYVIO is the first oral antihypertensive in a new therapeutic class to receive approval in nearly four decades. Learn more about TRYVIO/JERAYGO projected market size for resistant hypertension @ TRYVIO/JERAYGO Market Potential Resistant hypertension is defined as blood pressure that remains above target levels despite the concurrent use of three antihypertensive agents of different classes, ideally including a diuretic, at optimal doses. This condition affects approximately 10-20% of the hypertensive population and is associated with a higher risk of cardiovascular events, stroke, and renal complications. The pathophysiology is often multifactorial, involving factors such as obesity, high salt intake, secondary hypertension causes, and medication nonadherence. Managing resistant hypertension is challenging due to its complex etiology, requiring a more personalized and multidisciplinary approach. The current treatment paradigm includes intensifying lifestyle interventions, ensuring optimal diuretic use, and exploring secondary causes. In recent years, device-based therapies such as renal denervation and baroreceptor activation therapy have emerged as potential options for select patients, although uptake has been cautious due to mixed clinical trial results. Pharmaceutical innovation has been relatively limited, but there is renewed interest in novel drug classes such as aldosterone synthase inhibitors, endothelin receptor antagonists, and dual-acting agents. The future market outlook is positive, driven by an aging global population, increasing prevalence of obesity and diabetes, and heightened awareness of cardiovascular risk. We expect the resistant hypertension market to grow steadily, with significant commercial opportunity for both drug developers and medtech innovators offering targeted, evidence-based solutions. Discover more about the resistant hypertension market in detail @ Resistant Hypertension Market Report Emerging Competitors of TRYVIO/JERAYGO Some of the competing emerging key players include AstraZeneca (Baxdrostat), Mineralys Therapeutics (Lorundrostat), Tenax Therapeutics (TNX-103), and others. In March 2025, Tenax Therapeutics, Inc. announced that the FDA had completed its review of the company's revised Phase 3 development strategy for TNX-103 (oral levosimendan). This included approval of an amendment to expand patient enrollment and enhance the statistical power of the ongoing Phase III LEVEL trial, as well as the protocol for LEVEL-2, Tenax's second registrational Phase III study. The company stated that it now plans to enroll 230 patients in the LEVEL study, boosting the study's statistical power to over 95%. LEVEL-2, a global trial, is expected to launch in 2025. In March 2025, Mineralys Therapeutics, Inc. reported comprehensive results from the Phase II Advance-HTN trial, one of two key studies assessing lorundrostat in patients with confirmed uncontrolled hypertension (uHTN) or resistant hypertension (rHTN). In this trial, the 50 mg dose of lorundrostat achieved an absolute reduction of 15.4 mmHg in blood pressure and a placebo-adjusted reduction of 7.9 mmHg at week 12. The treatment also showed a favorable safety and tolerability profile, with only minor changes observed in potassium, sodium, and eGFR levels, and a low rate of treatment discontinuation. To know more about the number of competing drugs in development, visit @ TRYVIO/JERAYGO Market Positioning Compared to Other Drugs Key Milestones of TRYVIO/JERAYGO In March 2025, Idorsia announced that the US FDA had fully released TRYVIO from its REMS (Risk Evaluation and Mitigation Strategy) requirement. 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. In January 2025, Medicines and Healthcare Products Regulatory Agency (MHRA) approved JERAYGO to treat hypertension (high blood pressure) in adults whose blood pressure cannot be adequately controlled by at least three other medicines (also known as resistant hypertension), in the UK. In July 2024, Idorsia received approval from the European Commission for JERAYGO for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure control. In March 2024, Idorsia announced that the US Food and Drug Administration (FDA) has approved TRYVIO 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. The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food. It was made commercially available in the US in October 2024. Discover how TRYVIO/JERAYGO is shaping the resistant hypertension treatment landscape @ TRYVIO/JERAYGO Medication TRYVIO/JERAYGO Market Dynamics TRYVIO (also marketed as JERAYGO in select markets) is a promising therapeutic entrant in the treatment landscape for resistant hypertension, representing a novel mechanism of action targeting the aldosterone pathway. As a selective aldosterone synthase inhibitor, TRYVIO addresses a key pathophysiological driver in resistant hypertension—aldosterone excess—offering a more targeted approach compared to traditional mineralocorticoid receptor antagonists (MRAs) like spironolactone or eplerenone. This differentiation positions TRYVIO as an important alternative for patients who are intolerant to MRAs or who do not achieve adequate blood pressure control despite existing therapies. TRYVIO's entry comes at a time when the hypertension market is seeing renewed attention toward personalized, mechanism-based treatments. Early clinical trial data have demonstrated meaningful reductions in systolic blood pressure with a favorable safety and tolerability profile. This has led to increasing interest among specialists in cardiology and nephrology. TRYVIO's potential to be used alongside existing antihypertensive agents without significant drug-drug interactions is a key advantage. However, uptake may be moderated in the short term by p hysician familiarity with MRAs, payer scrutiny on pricing, and the need for broader real-world data to confirm long-term efficacy and safety. From a regulatory standpoint, TRYVIO/JERAYGO has gained approvals in several major markets, including the U.S. and EU, with regulatory filings underway in Asia-Pacific regions. Payers are cautiously optimistic, with reimbursement being granted in many geographies based on unmet needs and pharmacoeconomic models projecting reductions in cardiovascular events and hospitalizations. That said, its premium pricing compared to generics necessitates the generation of robust health economic data to support its value proposition, especially in cost-sensitive healthcare systems. Looking ahead, TRYVIO is well-positioned to capture a substantial share of the resistant hypertension market, particularly as guidelines begin to incorporate newer therapeutic classes. We forecast steady growth driven by expanding physician adoption, increasing diagnosis of resistant hypertension, and potential label expansion into related indications such as heart failure with preserved ejection fraction (HFpEF). Strategic partnerships, post-marketing surveillance, and long-term outcome studies will be critical in shaping TRYVIO's competitive edge and sustaining momentum in a crowded but evolving treatment landscape. Dive deeper to get more insight into TRYVIO/JERAYGO's strengths & weaknesses relative to competitors @ TRYVIO/JERAYGO Market Drug Report Table of Contents Related Reports Resistant Hypertension Pipeline Resistant Hypertension Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key resistant hypertension companies, including Idorsia Ltd, Janssen Biotech, Quantum Genomics SA, CinCor Pharma, Ionis Pharmaceuticals, and Vifor Pharma, among others. Hypertension Market Hypertension Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key hypertension companies such as Mineralys Therapeutics Inc., CinCor Pharma, among others. Hypertension Pipeline Hypertension Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key hypertension companies, including Gossamer Bio, Addpharma Inc., Insmed Incorporated, Alnylam Pharmaceuticals, 35Pharma Inc, Pfizer, Pharmosa Biopharm Inc., Guangzhou Magpie Pharmaceuticals Co., Ltd., Suzhou Sanegene Bio Inc., JW Pharmaceutical, among others. Treatment-Resistant Hypertension Market Treatment-Resistant Hypertension Market Insight, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key TRD companies such as Ionis Pharmaceuticals, KBP Biosciences, among others. 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

Allschwil, Switzerland – April 9, 2025 Idorsia Ltd (SIX: IDIA) today 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). 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 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. Michael Moye, President and General Manager of Idorsia US, commented: “The fact that the FDA has expedited the approval of the updated TRYVIO label to remove the REMS requirements is, I believe, a testament to the importance of TRYVIO. 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. The durable efficacy was achieved with a good safety and tolerability profile. Decreasing BP to such an extent in these high cardiovascular risk patients is known to markedly decrease the risk of fatal and non-fatal cardiovascular events, such as strokes and myocardial infarctions. Idorsia will now work with a sense of urgency to make TRYVIO available in retail pharmacies and simplify the administration for prescribers, distributors, and ultimately for patients." For the updated TRYVIO labeling, please see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). TRYVIO is 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 aprocitentan Aprocitentan 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 Idorsia Idorsia 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 contact: Investor & Media Relations Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil +41 58 844 10 10 investor.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

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