Larindrostat
Reading File
Searching the Web
larindrostat drug mechanism clinical trials
Searching PubMed
larindrostat
Searching PubMed
lorundrostat aldosterone synthase inhibitor hypertension
Reading Web Page
lorundrostat mechanism dose efficacy safety aldosterone synthase inhibitor
It looks like you meant lorundrostat (sometimes written as MLS-101). There is no known drug called "larindrostat" - this appears to be a misspelling. Here is a full overview:
Lorundrostat (MLS-101)
What It Is
Lorundrostat is a novel, orally administered aldosterone synthase inhibitor (ASI) developed for the treatment of uncontrolled and treatment-resistant hypertension. It is investigational as of mid-2026, with Phase 3 trial results published in JAMA (2025).
Mechanism of Action
Lorundrostat selectively inhibits CYP11B2 (aldosterone synthase), the enzyme responsible for the final step in aldosterone biosynthesis. This directly reduces aldosterone production, which in turn:
- Decreases sodium and water retention
- Lowers blood pressure via reduced plasma volume and vascular resistance
This is a fundamentally different approach than:
- MRAs (e.g., spironolactone, eplerenone) - which block the mineralocorticoid receptor
- ACE inhibitors / ARBs - which act upstream on the renin-angiotensin system
A key advantage over the first-generation ASI osilodrostat is that lorundrostat is highly selective for CYP11B2 over CYP11B1 (11-beta-hydroxylase), so it does not significantly suppress cortisol production.
Target Population
Patients with:
- Uncontrolled hypertension on 2-5 antihypertensive agents
- Treatment-resistant hypertension (TRH)
- High-risk subgroups: obesity, metabolic syndrome, obstructive sleep apnea - conditions where the normal aldosterone-renin feedback loop is disrupted, leading to autonomous aldosterone excess
Clinical Trial Data
| Trial | Phase | Key Finding |
|---|---|---|
| Target-HTN (NCT05001945) | 2 | Lorundrostat 50 mg/day significantly reduced office systolic BP; 50 mg had similar BP-lowering effect to 100 mg with fewer adverse events. No cortisol insufficiency. Published in JAMA 2023. [PMID: 37690061] |
| NEJM Phase 2 (2025) | 2 | Confirmed efficacy and safety in uncontrolled hypertension. [PMID: 40267417] |
| Launch-HTN (NCT06153693) | 3 | Phase 3 multicenter RCT (159 sites, 13 countries, enrolled Nov 2023-Sep 2024). Primary outcome: change in automated office systolic BP at week 6 (50 mg vs. placebo). Demonstrated efficacy and safety. Published in JAMA Aug 2025. [PMID: 40587141] |
Dosing
- Starting dose: 50 mg once daily
- Dose escalation to 100 mg available if needed (in Launch-HTN, ~34% of the 50 mg arm were escalated)
- Oral administration
Safety / Adverse Effects
- Hyperkalemia - elevated serum potassium (main concern; managed with dose reduction or discontinuation)
- Hyponatremia - one serious AE requiring discontinuation in Target-HTN
- No cortisol insufficiency - key advantage over osilodrostat
- Generally mild adverse event profile
Context in the Drug Class
The ASI class has gained momentum with several agents in development:
- Osilodrostat - first ASI, but non-selective; suppresses cortisol, limiting use in hypertension
- Baxdrostat - highly selective CYP11B2 inhibitor, similar profile to lorundrostat, positive Phase 2 data
- Lorundrostat - now with Phase 3 data supporting efficacy in treatment-resistant hypertension
Two recent systematic reviews (2025) have further evaluated this class in resistant hypertension [PMIDs: 40693351, 40885884].
Bottom line: Lorundrostat represents a promising new mechanism for patients with difficult-to-control hypertension, particularly those with aldosterone excess or obesity-driven renin suppression. Phase 3 data from the Launch-HTN trial (JAMA 2025) supports its efficacy and tolerability added on top of 2-5 existing antihypertensives.
Did you want more detail on any specific aspect - mechanism, trial results, comparison to MRAs, or the regulatory status?
This is a shared conversation. Sign in to Orris to start your own chat.