Natriuretic Peptide Receptor-1 Agonist for Resistant Hypertension: A Randomized Phase 2 Trial
Authors' conclusion
XXB750, an NPR-1 agonist, had a neutral effect on 24-hour ambulatory SBP in patients with resistant hypertension, despite showing a robust dose-response relationship for engagement of the target of pharmacologic action as indicated by increases in cyclic guanosine monophosphate levels.
Study context
- Population
- Patients with resistant hypertension (24-h systolic BP (SBP) ≥135 mm Hg despite 3 or 4 guideline-directed antihypertensive agents)
- Participants
- 189 patients
- Comparison
- XXB750 vs placebo
- Primary endpoint
- Dose-response relationship of XXB750 vs placebo in reducing mean 24-h SBP from baseline
- Follow-up
- Week 12
Methodological detailsphase 2, multicentre, double-blind, placebo-controlled, dose-finding
- Phase 2
- Multicentre
- Double-blind
- Placebo-controlled
- Dose-finding
Primary result
As reported in the abstract
Change in mean 24-h SBP
- No significant dose-dependent change from baseline in mean 24-h SBP
- No dose of XXB750 had a greater blood pressure (BP)-lowering effect than placebo
Further findings
Target engagement (plasma XXB750, plasma and urine cGMP) · week 12
- Plasma XXB750 concentrations and plasma and urine cyclic guanosine monophosphate increased dose-dependently
Anti-drug antibodies
- Changes in ambulatory BP not affected by anti-drug antibodies
Urinary sodium excretion and plasma renin
- No change in urinary sodium excretion; small increases in plasma renin with XXB750
Adherence to background antihypertensives (drug assays, 88 patients) · baseline and week 12
- Consistent across all treatment groups
Original publication
Natriuretic Peptide Receptor-1 Agonist for Resistant Hypertension: A Randomized Phase 2 Trial. J Am Coll Cardiol. Published 21 January 2026. doi:10.
Summarised from the published abstract; every number is checked against it