A Proof of Concept and Dose-finding Study of XXB750 in Patients With Heart Failure

Phase 2 Terminated 136 enrolled Novartis Pharmaceuticals

RandomizedParallel-groupDouble-blindTreatment

Summary

This was a multicenter, randomized, placebo- and active-controlled, parallel-group, 24-week trial to investigate the efficacy, safety, and tolerability of XXB750 in participants with HFrEF/HFmrEF.

Timeline

Start: 2023-12-12
Primary completion: 2024-11-01
Completion: 2024-11-01

Outcome

Missed primary endpoint

Stopped (Business): “Sponsor Decision”

paper In contrast to the expected mechanism of drug action, XXB750 treatment led to increased NT-proBNP levels PMID 41912806 ↗

Publications

Solomon SD, McMurray JJV, Felker GM, Januzzi JL, Lam CSP, Voors AA, Claggett B, Nuehrenberg TG, Rizkala AR, Koch C, Zhu W, Lefkowitz MP. The NPR1 agonist antibody XXB750 in heart failure: a phase 2 randomized trial. Nat Med. 2026 May;32(5):1694-1700. doi: 10.1038/s41591-026-04313-w. Epub 2026 Mar 30.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Sacubitril/valsartan	Unknown	97 mg	—
Comparator	Sacubitril/valsartan	Unknown	103 mg	—
Subject	XXB750	Monoclonal antibody	60 mg	Subcutaneous
Subject	XXB750	Monoclonal antibody	120 mg	Subcutaneous
Subject	XXB750	Monoclonal antibody	240 mg	Subcutaneous