Swissmedic has approved Idorsia’s Jeraygo (aprocitentan) for resistant hypertension in adults, to be used alongside at least three antihypertensive agents. The once-daily oral endothelin receptor antagonist is the first and only therapy in its class for systemic hypertension, with a recommended 12.5 mg starting dose and an option to uptitrate to 25 mg for tighter control. The decision is underpinned by a phase 3 program showing statistically significant reductions in systolic and diastolic blood pressure versus placebo, durability through withdrawal phases, and consistent effects across high-risk subgroups.
The approval raises a timely strategic question: can a novel pathway—long validated in pulmonary arterial hypertension but absent from systemic hypertension—reshape fourth-line therapy in a market dominated by generics and devices? After more than three decades without a new systemic mechanism in hypertension, an endothelin-based approach arrives as clinicians juggle spironolactone, SGLT2 inhibitors in select populations, and the growing appeal of renal denervation. The clinical opportunity is clear—roughly 10% of hypertensive patients meet criteria for resistant disease—yet the commercial and clinical hurdles are equally stark, from edema management to payer skepticism in a cost-contained primary care setting.
For patients with comorbid obesity, type 2 diabetes, and chronic kidney disease, resistant hypertension drives disproportionate cardiovascular and renal risk. Jeraygo’s profile, including rapid onset and sustained effect in a complex cohort, positions it for cardiology and nephrology uptake where therapeutic inertia is costly. However, safety trade-offs, particularly fluid retention, will demand clear protocols for diuretic optimization and patient selection. Medical Affairs teams will need to operationalize unattended automated office and ambulatory blood pressure monitoring in practice, reinforce exclusion of pseudo-resistance, and delineate sequencing relative to mineralocorticoid receptor antagonists and other adjuncts. Pregnancy contraindications and hepatic impairment restrictions add another layer of field education.
Commercially, Switzerland becomes a pivotal test bed for real-world durability, adherence, and payer value narratives. Idorsia is pursuing partnerships to broaden availability across Europe, aligning with its approach in larger markets where aprocitentan is commercialized as Tryvio in the United States and as Jeraygo in the EU and UK. Divergent labels—systemic hypertension in the US versus resistant hypertension in Europe—will shape positioning, messaging, and health economic modeling. With hypertension spending anchored in low-cost generics, access will hinge on demonstrating reductions in downstream events, renal function preservation in CKD, and potentially fewer interventional referrals, supported by pragmatic RWE programs and registry tie-ins.
This approval also threads into broader industry currents: the cardiometabolic renaissance is not confined to GLP-1s. New mechanisms targeting entrenched, high-prevalence diseases are re-emerging as viable growth engines, even as capital constraints force creative asset monetization and partnering. Idorsia’s transfer of aprocitentan rights to an affiliate to service financing needs underscores how balance sheet engineering and commercialization strategy now move in lockstep. Larger cardiometabolic franchises may view an ERA foothold in resistant hypertension as an acquisition or co-commercialization opportunity, especially if outcomes data mature favorably.
What comes next will decide Jeraygo’s class-defining potential: Swiss reimbursement decisions and formulary criteria, European partnering execution, ESC/ESH guideline updates on sequencing versus spironolactone and renal denervation, and the initiation—or readout—of cardio-renal outcomes studies that convert blood pressure gains into hard endpoints. If endothelin antagonism can prove event reduction at scale, hypertension’s therapeutic algorithm may be poised for its most meaningful reset in a generation.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
