Daridorexant hydrochloride

Aprocitentan, on top of background therapy, showed clinically meaningful and durable blood pressure (BP) reduction and a decrease in proteinuria in Black patients with confirmed resistant hypertension Allschwil, Switzerland – April 9, 2025 Idorsia Ltd (SIX: IDIA) today announced the publication of "Aprocitentan for Blood Pressure Reduction in Black Patients” in the April edition of Hypertension1. The publication reports preplanned analyses of the efficacy, tolerability and safety of aprocitentan – Idorsia’s once-daily, orally active, dual endothelin receptor antagonist – in the subgroup of African American patients enrolled in the Phase 3 PRECISION study2 in patients with confirmed resistant hypertension. Aprocitentan, when added to a combination of at least three antihypertensive drugs (four in more than 50% of patients), produced clinically meaningful and sustained blood pressure reductions.1 Aprocitentan also markedly decreased proteinuria in the patients with proteinuria at baseline.1 As reported by the authors, aprocitentan was safe and well tolerated, even in those Black patients with chronic kidney disease.1 Hypertension is the leading modifiable cause of early mortality and cardiovascular disease worldwide, impacting an estimated 1.3 billion people globally.3 Approximately 10% of these people have uncontrolled BP, despite receiving at least three antihypertensive medications from different classes, at optimal doses.4,5 Compared with adults whose hypertension is well controlled, adults with uncontrolled hypertension have much greater risk of heart attack, stroke, end-stage renal disease and death.6 Black hypertensive individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk.7,8,9 The endothelin (ET) pathway has been implicated in the pathogenesis of hypertension and is activated in patients prone to developing resistant hypertension,10,11 such as Black or African American patients12, patients with obesity13 or obstructive sleep apnea,14 and in comorbid conditions frequently associated with resistant hypertension such as diabetes15,16 and chronic kidney disease.17,18 Prof. Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA Professor, Tulane University School of Medicine, Tulane Heart & Vascular Institute, US, co-author of the publication and investigator in the PRECISION study, commented: “Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. This is possibly related to the activated endothelin system seen in patients prone to developing resistant hypertension and this may explain why existing therapies that do not target the endothelin system have not shown optimal improvement for Black patients. Now, for the first time, we have an approved treatment targeting the endothelin system that may help fulfil an unmet need in Black patients with resistant hypertension.” The publication is accompanied by an Editorial entitled “Endothelin Antagonism: A New Era for Resistant Hypertension?”19 from Gavin B. Chapman and Neeraj Dhaun of Edinburgh Kidney, University/BHF Centre for Cardiovascular Science, The Queen’s Medical Research Institute, University of Edinburgh, United Kingdom and Department of Renal Medicine, Royal Infirmary of Edinburgh, United Kingdom (G.B.C., N.D.). The Editorial recognizes that the approval of aprocitentan in the US and Europe represents the first new antihypertensive to be approved in over two decades and the first via a new pathway in almost four decades. In closing, the authors conclude “Given the broad beneficial effects ET receptor antagonism has on a range of cardiovascular risk factors, it may not be long before clinicians reach for these drugs above other, more established antihypertensive medications.”19 Prof. John M. Flack, MD, MPH, FAHA, MACP, CHS, Sergio Rabinovich Endowed Chair of Internal Medicine, Chair Departments of Medicine and Population Science and Policy, Southern Illinois University School of Medicine, Lead author of the publication and investigator in the PRECISION study, commented: “The salt-sensitive, low-renin, hypertension often seen in Black patients makes their hypertension difficult to control and increases their cardiovascular risk. In fact, Black adults with hypertension less often achieve the guideline recommended BP goals, leading to an estimated 400,000 strokes, heart attacks and other cardiovascular events that could be prevented over 10 years if blood pressure control could be achieved. In PRECISION, the effect of aprocitentan for these patients was striking and I agree with the Editorial in suggesting that we are entering a new “era” for resistant hypertension, as with aprocitentan, the dual endothelin receptor antagonist or “ERA”, we can now tackle this important pathway.” Aprocitentan is approved as TRYVIO™ in the US 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, and has been commercially available since October 2024.20 Aprocitentan is approved as JERAYGO™ for the treatment of resistant hypertension in combination with other antihypertensives in the European Union21 and the UK and marketing authorization applications are under review in Canada and Switzerland. Notes to the editor About Prof. Ferdinand Keith C. Ferdinand, MD, FACC, FAHA, FASH, FNLA began his medical career with a BA in biology from the University of New Orleans. He then went on to earn an MD from Howard University College of Medicine in Washington, DC, an internship at the US Public Health Hospital in New Orleans, an internal medicine residency and cardiology fellowship at LSU Medical Center and a cardiology fellowship at Howard University Hospital, Washington, D.C. After years of doing clinical work, research and teaching at Xavier University, LSU, Baylor College of Medicine, and Emory University, Dr. Ferdinand returned to New Orleans as a Professor of Clinical Medicine at the Tulane University Heart and Vascular Institute. Dr. Ferdinand has been heavily involved in many national organizations concerned with public health, including the Association of Black Cardiologists, of which he was the former Chair and Chief Science Officer, the American Society of Hypertension, of which he was a board member, and the Healthy Heart Community Prevention Program, a cardiovascular risk program targeting African American and other high-risk populations. He is the immediate-past Chair of the National Forum for Heart Disease and Stroke Prevention, which provides the leadership and encouragement for collaboration among over 65 organizations. Dr. Ferdinand focuses largely on cardiac risk factor evaluation and control, especially hypertension and hyperlipidemia, including communities of racial and ethnic minorities. He has had over 100 manuscripts published and has a strong media presence. His passion for patient-care is highlighted in his commitment to non-profit work and community service. In 2015 he was inducted into the Association of University Cardiologists. Prof. Ferdinand serves as a consultant to Idorsia. About Prof. Flack John M. Flack, M.D., M.P.H., F.A.H.A., M.A.C.P., an Alpha Omega Alpha (AOA) graduate of the University of Oklahoma School of Medicine, is the Sergio Rabinovich Endowed Chair of Internal Medicine and the Professor and Chair of the Department of Medicine at Southern Illinois University School of Medicine. He is also Chief of the Hypertension Section. He is a board-certified Internal Medicine specialist and an internationally renowned hypertension specialist/cardiovascular epidemiologist with widely recognized clinical/research expertise in hypertension in African Americans, resistant/refractory hypertension, device-based therapies for hypertension and racial cardiovascular health disparities. Dr. Flack is the current President of the American Hypertension Specialist Certification Program. He has published over 210 peer-reviewed manuscripts and book chapters and is an Associate Editor for the American Journal of Hypertension. He maintains an active clinical practice in complex hypertension at SIU where he teaches and mentors medical students and residents and undertakes innovative, cutting-edge research. Dr. Flack has received numerous awards including the Distinguished Research Award (1993) from the International Society on Hypertension in Blacks (ISHIB), the Daniel D. Savage Memorial Scientific Award (1998) from the Association of Black Cardiologist (ABC), the F. Dewey Dodrill Award for Excellence (2007) from the American Heart Association (AHA), the Detroit News Michiganian of the Year (2009), and the University of Oklahoma Academic Physician of the Year (2012). Also, he has been repeatedly named to Top Doctor, Best Doctor, and Super Doctor lists. Previously, he served a stint as a voting member of the FDA Cardio-Renal Advisory Board. Dr. Flack was recently conferred the status of Master by the American College of Physicians (ACP); he also is a current member of the ACP Board of Regents. Prof. Flack serves as a consultant to Idorsia. References 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

Daridorexant, Idorsia’s dual orexin receptor antagonist, shows consistent efficacy across both insomnia- and nocturia-related endpoints in a placebo-controlled study in patients with chronic insomnia and nocturia In this study, daridorexant was safe and well tolerated, consistent with the well-documented safety profile observed in the Phase 3 studies in chronic insomnia. The data from the Phase 4 study is published in the Journal of Sleep Research On World Sleep Day, Idorsia unites with the World Sleep Society in the call to make sleep health a priority March 14, 2025 Idorsia Ltd (SIX: IDIA) today announced the publication of “A randomized cross-over trial of daridorexant for the treatment of chronic insomnia and nocturia” in the Journal of Sleep Research. The new data provides evidence of the benefit of Idorsia’s dual orexin receptor antagonist, daridorexant (QUVIVIQ™), at a daily dose of 50 mg, in patients aged >=55 years with chronic insomnia and comorbid nocturia, with efficacy data on symptoms of both conditions, improvement in daytime functioning, and a good safety and tolerability profile.1 Chronic insomnia is defined as difficulty initiating and/or maintaining sleep at least three times a week for a minimum of three months and a significant negative impact on daytime functioning. Nocturia is waking during the night due to the need to urinate. Insomnia and nocturia frequently co-exist, particularly in older patients, and each may contribute to poor sleep quality, impaired daytime functioning and low quality of life. Katharina Lederer, MD, Advanced-Sleep-Research GmbH (ASR) in Berlin, Germany, and the coordinating investigator in the study, commented: “In patients needing to frequently visit the bathroom during the night, insomnia is very common and a significant burden for patients. The results that have been generated in this study are remarkable. Not only have we seen consistent efficacy after a short treatment period and across the insomnia measures – including increasing total sleep time and an impressive effect on insomnia severity – but also there was a great effect on their nocturia. What’s more, patients also experienced improved next-day functioning and consequently reported significantly higher satisfaction after treatment with daridorexant versus placebo. I hope that the ability to affect both comorbidities will encourage a more joined-up thinking for specialists of both conditions to adequately treat these patients.” José Emilio Batista, MD, Director of the Urology Department in Teknon Medical Center, Spain, and an investigator in the study, commented: “Many people visit the toilet during the night, go straight back to sleep and think nothing more of it. For these people, it is difficult to understand the impact that nocturia can have. The patients enrolled in this study are waking 3, 4 and sometimes 5 or more times during the night to use the toilet, so quite severe nocturia symptoms. When combined with insomnia, the patients are badly affected by the disruption, with many not able to function well the next day. The results in the study show that the patients are able to sleep longer before the first visit to the toilet and need to go fewer times, these are certainly clinically meaningful results.” In total, 60 patients – equally split between male and female patients – aged 55 or older with insomnia and comorbid nocturia participated in this multi-national, multi-center, double-blind, randomized, placebo-controlled, 2-way cross-over study. The study consisted of 2 treatment periods of 4 weeks each, separated by a 2-3-week washout period. In the study, daridorexant 50 mg significantly improved subjective total sleep time (sTST) from baseline to Week 4 of treatment (primary endpoint) and other measures of sleep and daytime functioning. Insomnia Severity Index (ISI) score was reduced, with one and a half as many patients treated with daridorexant vs placebo improving by ≥6 units, the threshold of clinical relevance. The impact of insomnia on patients’ daytime functioning was measured daily using the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Improvements in sTST, quality and depth of sleep, and daytime functioning were seen as early as Week 1 of treatment and were maintained throughout the treatment period.1 Treatment with daridorexant 50 mg also reduced the number of nocturnal voids (nighttime visits to the toilet) from baseline to Week 4 and improved other nocturia-related symptoms, such as an increase in time to first void. A short time to first void is associated with increased daytime dysfunction and decreased sleep quality, quantity and/or sleep efficiency.1 Daridorexant 50 mg in patients with chronic insomnia and comorbid nocturia was safe and well tolerated1, consistent with the well-documented safety profile observed in the Phase 3 studies in chronic insomnia2. No serious AEs/AEs leading to discontinuation were reported in the study. Importantly, in terms of adverse events of special interest, there were no urinary incontinences, and no falls observed in patients treated with daridorexant.1 Antonio Olivieri, MD, Chief Medical Officer & Head of Global Medical Affairs, commented: “We already have incredibly strong and robust data demonstrating that daridorexant is an effective treatment of insomnia disorder with an optimal duration of action and a well-documented safety profile. Nonetheless, I am very impressed with the study results because here we see that daridorexant has a positive effect on both insomnia and nocturia endpoints. After a short treatment period, patients reported a significant improvement on the quality of their nights’ sleep and importantly, also on their days. I am very proud that Idorsia is leading the way in building evidence on the burden of insomnia and furthering the science of sleep.” World Sleep Day Today marks World Sleep Day, a significant annual awareness event within the global sleep community. Sleep is one of the three key pillars of health, alongside healthy diet and exercise, and lays the foundation to our physical, mental, and social well-being. Sleep disorders such as insomnia can lead to a lack of quality, restorative sleep. When people experience problems falling or staying asleep for at least three days a week, for at least three months with significant impact on their daytime activities, their insomnia is defined as chronic. Despite 6-10% of adults living with chronic insomnia, the condition is often not recognized, and the negative impact underestimated. Benjamin Limal, President of Europe and Canada region, commented: “All of us at Idorsia are proud supporters of World Sleep Day, and we are united with the World Sleep Society in the call to action to make sleep health a priority. We support patients, advocates and the medical community in elevating the conversation around sleep and emphasizing the significant, and often hidden, impact chronic sleep disorders have on individuals and society.” To access information and resources for people living with chronic insomnia, including a guide to help discuss symptoms with a doctor, visit World Sleep Day 2025. Daridorexant is Idorsia’s dual orexin receptor antagonist (DORA) which blocks the binding of the wake-promoting orexin neuropeptides. Rather than inducing sleep through broad inhibition of brain activity, daridorexant only blocks the activation of orexin receptors and reduces the overactive wake drive shown in individuals with chronic insomnia. Daridorexant is commercially available as QUVIVIQ in the US, Germany, Italy, Switzerland, Spain, the UK, Canada, Austria, France, Sweden, and Japan, and is approved throughout the EU, and in Hong Kong. In total, 60 patients – equally split between male and female patients – aged 55 or older with insomnia and comorbid nocturia participated in this multi-national, multi-center, double-blind, randomized, placebo-controlled, 2-way cross-over study. The study consisted of 2 treatment periods of 4 weeks each, separated by a 2-3-week washout period. The primary objective of the study was to assess the efficacy of daridorexant 50 mg daily on insomnia by measuring subjective total sleep time (sTST) by the Sleep Diary Questionnaire (SDQ). Other sleep-related endpoints included the overall rating of the insomnia severity by the Insomnia Severity Index© (ISI©), and SDQ-derived variables like quality of sleep visual analog scale (VAS), depth of sleep VAS, daytime alertness VAS, daily ability to function VAS, and number of awakenings. The secondary objective was to assess the efficacy of daridorexant on nocturia by evaluating the number of nocturnal voids, the time to the first nocturnal void, each voiding volume (nighttime and daytime) including total volume, lower urinary tract symptoms (LUTS) sub-score using the International Consultation on Incontinence Questionnaire (ICIQ) -MLUTS and -FLUTS for male and female subjects, and quality of life relative to nocturia, assessed by ICIQ Nocturia Quality of Life (ICIQ-NQoL). Other endpoints included a change in daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire score, IDSIQ). Other objectives focused on patient’s overall assessment ratings of their condition and symptoms, as well as patients’ safety using various questionnaires. Insomnia is defined as a combination of dissatisfaction with sleep and a significant negative impact on daytime functioning. Dissatisfaction with sleep refers to the difficulty to initiate and/or maintain sleep on at least three nights per week for at least three months, despite adequate opportunity to sleep.3 Insomnia is a condition of overactive wake signaling and studies have shown that areas of the brain associated with wakefulness remain more active during sleep in patients with insomnia. Insomnia is a common problem with a prevalence of approximately 10% worldwide. On this basis, and assuming a US adult population of around 250 million, there are approximately 25 million adults in the US who suffer from insomnia. Insomnia as a disorder is quite different from a brief period of poor sleep, and it can take its toll on both physical and mental health. It is a persistent condition with a negative impact on daytime functioning. Idorsia’s research has shown that poor-quality sleep can affect many aspects of daily life, including the ability to concentrate, mood, and energy levels. The goals of managing insomnia are to improve sleep quality and quantity, as well as daytime functioning. Current recommended treatment of insomnia includes sleep hygiene recommendations, cognitive behavioral therapy and pharmacotherapy. Nocturia is waking during the night due to the need to urinate and is considered clinically relevant if someone needs to urinate at least twice each night. It is one of the main causes of sleep disruption, including frequent awakenings with patients having difficulties returning to sleep.4 Already two or more voids per nights have been associated with significant burden for the patients and were linked to next day impairments. Nocturia is a predictor for insomnia, with an increased number of voids per night associated with worsened sleep quality and quality of life.5,6,7 Insomnia is common in patients suffering from frequent night-time voiding and should be adequately treated. There is a high unmet medical need to identify effective and safe treatments targeting the frequent sleep complaints in this patient population. References Lederer K et al. Journal of Sleep Research. 2025. doi: 10.1111/jsr.70002 Mignot E et al. Lancet Neurol. 2022;21(2):125-139. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed., Text Revision. American Psychiatric Publishing. 2022. Ancoli-Israel S, Bliwise DL, Nørgaard JP. The effect of nocturia on sleep. Sleep Med Rev. 2011;15(2):91-97. doi:10.1016/j.smrv.2010.03.002 Asplund R, Aberg H. Health of the elderly with regard to sleep and nocturnal micturition. Scand J Prim Health Care. 1992 Jun; 10(2):98-104. Bliwise DL, Foley DJ, Vitiello MV, Ansari FP, Ancoli-Israel S, Walsh JK. Nocturia and disturbed sleep in the elderly. Sleep Med. 2009 May; 10(5):540-8. Yu HJ, Chen FY, Huang PC, Chen TH, Chie WC, Liu CY. Impact of nocturia on symptom-specific quality of life among community-dwelling adults aged 40 years and older. Urology. 2006 Apr; 67(4):713-8 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. The content above comes from the network. if any infringement, please contact us to modify.