Idorsia Pharmaceuticals U.S. Inc. announced today that the US Food and Drug Administration (FDA) has approved TRYVIO™ (aprocitentan) 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.
| Ad hoc announcement pursuant to Art. 53 LR
RADNOR, Pa., March 20, 2024 /PRNewswire/ -- Idorsia Pharmaceuticals US Inc. announced today that the US Food and Drug Administration (FDA) has approved TRYVIO™ (aprocitentan) 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.1 Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.1 The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food.1
Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia commented: TRYVIO (aprocitentan) is an endothelin receptor antagonist that inhibits the binding of endothelin (ET)-1 to ETA and ETB receptors.1,2 The effects of ET-1 bear many similarities with the pathophysiology of hypertension,3 and ET-1 is a major driver of aldosterone production.4 Until the approval of TRYVIO, no systemic antihypertensive medications targeted the ET pathway,5 as approved antihypertensive therapies focus on the regulation of salt and water (diuretics), antagonism of the renin–angiotensin–aldosterone (RAAS) system, reduction of influx of extracellular calcium into the cell (calcium channel blockers), sympatholytic activity (beta blockers, central alpha-agonist agents), or non-selective vasodilatory effects.6,7 TRYVIO was evaluated as a monotherapy in a Phase 2 study in patients with hypertension,8 and as an add-on therapy in a Phase 3 study called PRECISION in patients with confirmed resistant hypertension.9 In PRECISION, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4, with a sustained effect at week 40.10 Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented: Michael A. Weber, MD, Professor of Medicine, Division of Cardiovascular Medicine State University of New York, and an investigator in the PRECISION study commented: Phase 3 clinical study1,9,10 Following the 4-week placebo run-in period, 730 patients were randomized equally to aprocitentan at either 12.5 mg, 25 mg, or placebo once daily during the initial 4-week double-blind (DB) treatment period (part 1). At the end of 4 weeks, all patients entered the single-blind treatment period (part 2) where they received 25 mg aprocitentan once daily for 32 weeks. At the end of the 32 weeks, patients were re-randomized to receive either 25 mg aprocitentan or placebo, once daily, during a 12-week DB-withdrawal period (part 3). The primary efficacy endpoint was the change in sitting SBP (SiSBP) from baseline to Week 4 during part 1, measured at trough by unattended automated office blood pressure (uAOBP). The key secondary endpoint was the change in SiSBP measured at trough by uAOBP from Week 36 (i.e., prior to randomized withdrawal to 25 mg aprocitentan or placebo in part 3) to Week 40. Patients had a mean age of 62 years (range 24 to 84 years) and 60% were male. Patients were White (83%), African American (11%) or Asian (5%). Approximately 10% were Hispanic. The mean body mass index (BMI) was 34 kg/m2 (range 18 to 64 kg/m2). At baseline, 19% of patients had an eGFR 30–59 mL/min/1.73 m2 and 3% had an eGFR 15–29 mL/min/1.73 m2. At baseline, 24% of patients had a urine albumin-to-creatinine ratio (UACR) of 30–300 mg/g and 13% had a UACR >300 mg/g. Approximately 54% of patients had a medical history of diabetes mellitus, 31% ischemic heart disease, and 20% congestive heart failure. At baseline, 63% of patients reported taking four or more antihypertensive medications. TRYVIO 12.5 mg was statistically superior to placebo in reducing SiSBP at Week 4 (part 1). The treatment effect was consistent for sitting diastolic BP (SiDBP). The persistence of the BP-lowering effect of TRYVIO was demonstrated in part 3 of the trial, in which patients on aprocitentan were re-randomized to placebo or 25 mg aprocitentan following a period during which all patients were treated with 25 mg. In patients re-randomized to placebo, the mean SiSBP increased, whereas in patients re-randomized to 25 mg aprocitentan the mean effect on SiSBP was maintained and was statistically superior to placebo at Week 40. The treatment effect was consistent for SiDBP. Most of the BP-lowering effect occurred within the first two weeks of treatment with TRYVIO. TRYVIO is not approved for use at a 25 mg dose. The efficacy for the 25 mg aprocitentan dose as measured in the primary end point of change in sitting SBP (SiSBP) from baseline to Week 4 in part 1, was similar to the 12.5 mg dose and thus aprocitentan 12.5 mg is the approved dose. TRYVIO’s BP-lowering effect appeared consistent among subgroups defined by age, sex, race, BMI, baseline eGFR, baseline UACR, medical history of diabetes, and between BP measurement methodologies (uAOBP and ambulatory BP measurements). The most frequently reported adverse reactions to TRYVIO during the 4-week double-blind placebo-controlled treatment period (part 1) of the PRECISION study were edema/fluid retention and anemia. During the initial 4-week double-blind placebo-controlled treatment period (part 1), 0.8% of patients experienced an adverse reaction of hypersensitivity (i.e., rash, erythema, allergic edema) on TRYVIO compared to no reports in patients treated with placebo. One patient experienced allergic dermatitis requiring hospitalization while receiving aprocitentan 25 mg. TRYVIO is contraindicated in patients who are hypersensitive to aprocitentan or any of its excipients. Use of TRYVIO is contraindicated in pregnancy. Lowering BP reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. There are no controlled trials demonstrating reduction of risk of these events with TRYVIO. Alberto Gimona, MD and Head of Global Clinical Development of Idorsia, commented: Tosh Butt, President and General Manager of Idorsia US commented: The team at Idorsia has been working on the research and development of endothelin receptor antagonists for more than 30 years, successfully bringing three other molecules from this class to patients in different indications. ET-1, via its receptors (ETA and ETB), mediates a variety of deleterious effects such as vasoconstriction, fibrosis, cell proliferation, and inflammation. In hypertension, ET-1 can cause endothelial dysfunction, vascular hypertrophy and remodeling, sympathetic activation, and increased aldosterone synthesis.1 Martine Clozel, MD and Chief Scientific Officer of Idorsia, concluded: TRYVIO REMS Important Safety Information TRYVIO may cause serious side effects, including:
People can only receive TRYVIO through a restricted program called the TRYVIO REMS. If you are a person who can become pregnant, your healthcare provider will talk to you about pregnancy testing recommendations and the need to use acceptable birth control, the benefits and risks of TRYVIO, and the need to report suspected pregnancy right away to your healthcare provider. What is TRYVIO? Do not take TRYVIO if you are
Before taking TRYVIO, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. TRYVIO may cause other serious side effects, including:
Your healthcare provider may stop treatment with TRYVIO if you develop certain side effects. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of TRYVIO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). Notes to the editor About Dr Michael A. Weber, MD His career has been focused primarily on hypertension and preventive cardiology. He has published numerous research articles in the medical literature and has authored or edited 16 books. Together with Dr. Suzanne Oparil, he is responsible for the widely used reference volume, Hypertension. Dr. Weber is the Editor-in-Chief of The Journal of Clinical Hypertension. Dr. Weber was one of the founders of The American Society of Hypertension and has served as its President. He also served as Chair of the ASH Hypertension Specialists Program. He is a Fellow of The American College of Physicians, The American College of Cardiology and The American Heart Association. He has served on the Cardiovascular and Renal Drugs Advisory Board of the Food and Drug Administration, and continues as a consultant to that Agency. He has also served for ten years as Chairman of the Formulary Committee of a major pharmacy benefits provider serving many of the leading health plans in the United States. His main current research interests are in clinical trials of patients at high risk of cardiovascular events or strokes. He is also participating actively in trials in patients with metabolic disorders such as diabetes and kidney disease. Dr. Weber currently serves on the Steering Committees of several national and international clinical outcomes trials. Dr. Weber serves as a consultant to Idorsia. References
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Online Registration: LINK Webcast participants should visit Idorsia’s website www.idorsia.com 10-15 minutes before the webcast is due to start. About Idorsia US About Idorsia Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 20-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients. Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 800 highly qualified specialists dedicated to realizing our ambitious targets. 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.
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