Idorsia Ltd. announced that the European Commission has approved JERAYGO? (aprocitentan) 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 (BP) control. Hypertension is one of the leading causes of cardiovascular disease worldwide, impacting an estimated 1.3 billion people globally. Approximately 10% of these people have uncontrolled BP, despite receiving at least three antihypertensive medications from different classes, at optimal doses and they are categorized in hypertension guidelines as having resistant hypertension.

About the Phase 3 PRECISION study: The efficacy of aprocitentan was evaluated in one randomized, double-blind (DB), placebo-controlled Phase 3 multicenter study. Patients with uncontrolled blood pressure (systolic blood pressure [SBP] =140 mmHg) despite the use of at least three antihypertensive medicinal products and following exclusion of pseudo-resistant hypertension (e.g., white coat effect, inappropriate blood pressure measurement, secondary causes of hypertension) were considered to have resistant hypertension. The patients were switched to standardized background antihypertensive therapy consisting of an angiotensin receptor blocker (valsartan 160 mg), a calcium channel blocker (amlodipine 5 or 10 mg), and a diuretic (hydrochlorothiazide 25 mg) throughout the study.

Patients with concomitant use of beta-blockers continued this treatment throughout the study, in addition to the standardized background antihypertensive therapy and study treatment. A total of 730 patients received either aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo once daily during the initial 4-week DB treatment (part 1). Thereafter, patients received aprocitentan 25 mg once daily during the 32-week single-blind treatment (part 2).

At the end of the 32 weeks, patients were re-randomized to receive either aprocitentan 25 mg or placebo, once daily, during the 12-week double-blind withdrawal (DB-WD) treatment (part 3). The primary efficacy endpoint was the change in sitting SBP (SiSBP) from baseline to Week 4 during DB treatment (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 DB-WD baseline (Week 36) to Week 40 (part 3).

Patients had a mean age of 61.7 years (range 24 to 84 years; 34.1% were = 65 and < 75 years; 9.9% were = 75 years) and 59.5% were male. Patients were White (82.9%), African American (11.2%) or Asian (5.2%). The mean body weight was 97.6 kg (range 46 to 196 kg) and mean BMI was 33.7 kg/m2 (range 18 to 64 kg/m2).

Patients had a medical history of type 2 diabetes mellitus (54.1%), ischemic heart disease (30.8%), central nervous system vascular disorders (23.0%), chronic kidney disease stages 3 and 4 (22.2%; 19.3% of patients had eGFR 30?59 mL/min/1.73 m2 and 2.9% had eGFR 15?29 mL/min/1.73 m2), congestive heart failure (19.6%), and sleep apnea syndrome (14.1%). 63.0% of patients had four or more antihypertensive medicinal products. Key PRECISION findings: Doses of aprocitentan 12.5 and 25 mg showed a statistically significant reduction vs placebo on SiSBP at Week 4. The treatment effect was consistent for sitting diastolic blood pressure (SiDBP).

The persistence of the BP-lowering effect of aprocitentan was shown in DB-WD treatment (part 3). In patients re-randomized to placebo, the mean SiSBP increased, whereas in patients re-randomized to aprocitentan 25 mg the mean effect on SiSBP was stable, resulting in a statistically significant difference. The treatment effect was consistent for SiDBP.

The effect was also consistent across SBP and DBP measured by ambulatory BP monitoring (ABPM) and assessed as daytime, night-time, and 24h periods at Week 4 and Week 40. A substantial proportion (i.e., at least 90%) of the BP-lowering effect was observed within the first two weeks of treatment with aprocitentan. The effect of aprocitentan was consistent across subgroups of age (including patients = 75 years), sex, race (including patients with Black or African American origin), BMI, baseline urine albumin-to-creatinine ratio (UACR), baseline eGFR and medical history of diabetes.

The most frequently reported adverse reactions with aprocitentan were edema/fluid retention (mostly peripheral edema) (9.1%, 12.5 mg; 18.4%, 25 mg) and hemoglobin decreased (3.7%, 12.5 mg; 1.2%, 25 mg). JERAYGO is contraindicated for use in women who are pregnant, breast-feeding and in women of childbearing potential who are not using reliable contraception, and patients with severe hepatic impairment.