AZD3427 / AstraZeneca - LARVOL DELTA

AZD3427, a novel relaxin receptor agonist and impact on renal perfusion in patients with heart failure with reduced ejection rraction: the phase 1b Re-Perfuse study design (HEART FAILURE 2025) - "AZD3427, a long-acting relaxin analog and selective agonist of RXFP1, showed trends of increased stroke volume and estimated glomerular filtration rate (eGFR) in HF patients treated with AZD3427. Conclusion This study, alongside other ongoing AZD3427 studies, aims to evaluate the dual effects of AZD3427 in improving both cardiac and renal function. These insights could guide the development of future therapeutic strategies for managing HF and renal impairment."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

A novel long-acting relaxin-2 fusion, AZD3427, improves cardiac performance in non-human primates with cardiac dysfunction. (PubMed, Cardiovasc Res) - "Prolonged administration of AZD3427, a long-acting relaxin receptor RXFP1 agonist, resulted in remarkable improvement in cardiac function in a NHP model. Findings of this study are an important translational step to developing future therapies and support further clinical development of AZD3427 as a novel treatment for patients with heart failure (HF)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders

Re-PHIRE: A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2 (clinicaltrials.gov) - P2 | N=245 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re-PHIRE. (PubMed, ESC Heart Fail) - "Re-PHIRE is the first study of a relaxin mimetic in patients with PH-LHD. The insights gained from the Re-PHIRE study are expected to inform the further development of AZD3427 in the PH-LHD population, including identifying the most suitable pulmonary hypertension and HF phenotypes for treatment."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Re-PERFUSE: AZD3427 Effects on Renal Perfusion in Heart Failure Patients With Reduced Ejection Fraction and Renal Impairment (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Re-PERFUSE: AZD3427 Effects on Renal Perfusion in Heart Failure Patients With Reduced Ejection Fraction and Renal Impairment (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study. (PubMed, J Am Heart Assoc) - P1 | "AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long-term treatment for patients with heart failure."

Journal • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

AZD3427, a relaxin mimetic in pulmonary hypertension group 2 associated with left heart disease: design and rationale of the phase 2b Re-PHIRE Study (HEART FAILURE 2024) - "Re-PHIRE is the first study of a relaxin mimetic in PH-LHD. Insights gained from this study are expected to inform the further development of AZD3427 in the PH-LHD population."

P2b data • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Re-PHIRE: A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2 (clinicaltrials.gov) - P2 | N=220 | Recruiting | Sponsor: AstraZeneca | Phase classification: P2b ➔ P2

Phase classification • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Safety, pharmacokinetics, and pharmacodynamics of AZD3427, a functionally selective long acting relaxin mimetic agonist of the RXFP1 receptor (HEART FAILURE 2023) - "AZD3427 was generally well tolerated. These findings support further evaluation of AZD3427 in patients with HF."

Clinical • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

Re-PHIRE: A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2 (clinicaltrials.gov) - P2b | N=220 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CST3

Re-PHIRE: A Study of AZD3427 in Participants With Heart Failure and Pulmonary Hypertension Group 2 (clinicaltrials.gov) - P2b | N=220 | Not yet recruiting | Sponsor: AstraZeneca

New P2b trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CST3

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1 | N=105 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1 | N=104 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2022 ➔ Aug 2022 | Trial primary completion date: May 2022 ➔ Aug 2022

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Study to Evaluate the Effects of AZD3427 in Patients With Heart Failure (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: AstraZeneca; N=16 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Cardiovascular • Congestive Heart Failure • Heart Failure

Study to Evaluate the Effects of AZD3427 in Patients With Heart Failure (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: AstraZeneca; Trial completion date: Mar 2022 ➔ Aug 2022; Trial primary completion date: Mar 2022 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1; N=104; Recruiting; Sponsor: AstraZeneca; Trial completion date: Oct 2021 ➔ May 2022; Trial primary completion date: Oct 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • NPPB

Study to Evaluate the Effects of AZD3427 in Patients With Heart Failure (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: AstraZeneca; Trial completion date: Nov 2021 ➔ Mar 2022; Initiation date: Jun 2021 ➔ Oct 2021; Trial primary completion date: Nov 2021 ➔ Mar 2022

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

Study to Evaluate the Effects of AZD3427 in Patients With Heart Failure (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: AstraZeneca

Clinical • New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1; N=104; Recruiting; Sponsor: AstraZeneca; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427 (clinicaltrials.gov) - P1; N=104; Not yet recruiting; Sponsor: AstraZeneca

Clinical • New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure