The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial - PubMed
7 hours ago
- #NPR1 agonist
- #clinical trial
- #heart failure
- XXB750, a human monoclonal antibody targeting natriuretic peptide receptor 1 (NPR1), was evaluated in a phase 2 randomized trial for heart failure with reduced ejection fraction.
- Patients were randomized to receive 60 mg XXB750, 120 mg XXB750, placebo, or open-label sacubitril/valsartan, with NT-proBNP change at 16 weeks as the primary endpoint.
- Contrary to expectations, XXB750 increased NT-proBNP levels and decreased cGMP levels, while sacubitril/valsartan decreased NT-proBNP and increased cGMP.
- XXB750 was associated with more frequent death or worsening heart failure events (25%) compared to sacubitril/valsartan (8%) and placebo (0%), leading to premature trial termination.
- The results suggest XXB750 may paradoxically act as a functional antagonist of endogenous natriuretic peptides in heart failure patients.