Lorundrostat cut automated office systolic blood pressure by a mean 16.9 mmHg at Week 6 and 19.0 mmHg at Week 12 in the Phase 3 Launch-HTN trial, translating to placebo-adjusted reductions of 9.1 mmHg and 11.7 mmHg, respectively (p<0.0001 at both time points). Among 1,083 participants with uncontrolled or treatment‑resistant hypertension on two to five background agents, discontinuations due to adverse events were below 1% despite higher rates of hyponatremia, hyperkalemia, and reduced kidney function in the active arm. The core development is editorial, not regulatory: JAMA included the Launch-HTN manuscript in its inaugural Research of the Year Roundup, profiling the study as a notable advance in resistant hypertension. The global, randomized, double‑blind, placebo‑controlled trial tested the aldosterone synthase inhibitor as add‑on therapy at 50 mg once daily, with an option to uptitrate to 100 mg at Week 6 in one arm. The primary endpoint was change from baseline in systolic blood pressure at six weeks versus placebo, assessed by AOBP. The company notes effects were consistent across demographic and baseline treatment subgroups, with a trial population intentionally enriched for women, Black or African American, and elderly participants. Strategically, the recognition amplifies Mineralys’ positioning around aldosterone biology and differentiation from mineralocorticoid receptor antagonists that remain the default escalation in resistant hypertension. Enzyme inhibition upstream of the receptor aims to suppress excess aldosterone production while avoiding some receptor‑mediated tolerability issues, though electrolyte and renal signals will demand rigorous monitoring. The sponsor highlights high selectivity for CYP11B2 over cortisol synthase, an important narrative given historical concerns about off‑target effects with earlier agents. JAMA’s editorial spotlight strengthens the argument that blood pressure–centric endpoints with a clean daily oral regimen can still move the needle in a category crowded with incremental combinations and polypharmacy. For sites and CROs, the operational package looks straightforward: once‑daily oral dosing layered onto existing regimens, standardized AOBP procedures, and a clear uptitration decision at Week 6. The flip side is practical—potassium and renal function monitoring will be non‑negotiable in a population with substantial CKD comorbidity, and programs will need standing protocols for hyperkalemia management to keep discontinuations low in real‑world settings. The diversity of enrollment is a notable execution signal as agencies scrutinize representativeness; it also eases concerns about generalizability across common resistant‑hypertension phenotypes. For payers and guideline committees, the magnitude of placebo‑adjusted reduction and durability beyond 12 weeks will be weighed against spironolactone-based algorithms, intolerance rates, and total cost of monitoring. Next, attention shifts to durability and breadth. The open‑label Transform‑HTN extension should clarify long‑term safety, electrolyte management, and maintenance of effect. Explore‑OSA, which completed enrollment in patients with hypertension and moderate‑to‑severe sleep apnea, is slated to read out in the first quarter of 2026 and will test whether aldosterone synthase inhibition can touch nighttime systolic pressure and apnea‑hypopnea dynamics—an outcome with outsized relevance to cardiometabolic risk and 24‑hour control. Regulatory reviewers will also parse the reliance on AOBP as the primary endpoint and may look for ambulatory blood pressure profiles or additional functional readouts. Watch for the sponsor’s NDA timing, any requests for ABPM or additional safety datasets, and signals of how the agent performs in CKD‑heavy subgroups or in combination backbones. The key risks remain electrolyte management at scale and demonstration of sustained, clinically meaningful reductions that translate into adoption beyond specialist centers.
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.
