Heart failure & cardiomyopathiesRandomised controlled trial
The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial
- Randomised controlled trial
- placebo-controlled
- blinded (XXB750 vs placebo)
- open-label sacubitril/valsartan
- stopped prematurely on data monitoring committee recommendation
Data monitoring committee recommended stopping the trial prematurely because of excess HF events with XXB750
Authors' conclusion
In contrast to the expected mechanism of drug action, XXB750 treatment led to increased NT-proBNP levels, lowered cGMP levels and more worsening heart failure events, suggesting that XXB750 may paradoxically behave as a functional antagonist of endogenous natriuretic peptides in patients with heart failure.
Study context
- Population
- Patients with HF and LVEF <50% on background ACEi/ARB or sacubitril/valsartan70% male
- Participants
- 136 patients
- Comparison
- XXB750 vs placebo vs sacubitril/valsartan
- 60 mg XXB750n = 26
- 120 mg XXB750n = 55
- Placebon = 29reference
- Sacubitril/valsartann = 25
- Primary endpoint
- Change in NT-proBNP levels
- Follow-up
- 16 weeks after treatment initiation
Primary result
As reported in the abstract
NT-proBNP, ratio of change from baseline · 16 weeks
Pooled XXB750
1.34
ratio of change from baseline · 95% CI 1.07–1.66
Sacubitril/valsartan
0.70
ratio of change from baseline · 95% CI 0.45–1.10
Further findings
| Outcome | 60 mg XXB750 | 120 mg XXB750 | Placebo | Sacubitril/valsartan |
|---|---|---|---|---|
| cGMP, ratio of change from baseline · 16 weeks | Not reported in the abstract | Not reported in the abstract | Not reported in the abstract | ratio of change from baseline 1.38 (95% CI 1.13–1.69) |
| Death or worsening HF events | Not reported in the abstract | Not reported in the abstract | 0% | 8% |
- Cyclic guanosine monophosphate (cGMP), ratio of change from baseline: Pooled XXB750 ratio of change from baseline 0.77 (95% CI 0.65–0.91)
- Death or worsening HF events: XXB750 25%
- Death or worsening HF events: trial stopped prematurely on data monitoring committee recommendation for excess HF events with XXB750
Original publication
The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial. Nat Med. Published 30 March 2026. doi:10.1038/s41591-026-04313-w
Summarised from the published abstract; every number is checked against it