Patients with pulmonary hypertension linked to left heart disease (PH-LHD) face significantly worse outcomes, including higher rates of death and hospitalization, even when receiving guideline-directed heart failure treatments. This underscores a critical unmet medical need within this specific heart failure population.
AZD3427 is a new investigational drug that is a functionally selective, long-lasting mimetic of relaxin, a naturally occurring hormone known for its capacity to dilate blood vessels and prevent fibrosis (the excessive scarring or stiffening of tissues). A phase 1b study in heart failure patients demonstrated that AZD3427 has a favorable safety profile and good pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes the drug). Given these promising early results, AZD3427 is now being developed as a potential new therapy for PH-LHD.
The Re-PHIRE study, a phase 2b, randomized, double-blind, placebo-controlled, multicenter, dose-ranging study, is currently evaluating the drug’s effect across various PH-LHD phenotypes. The study will randomize 220 patients into 4 treatment groups, with participants receiving either a subcutaneous injection of AZD3427 or a placebo every 2 weeks for 24 weeks. The primary endpoint of the study is the change in pulmonary vascular resistance after 24 weeks of treatment. Key secondary endpoints will assess changes in mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, 6-minute walking distance, N-terminal pro B-type natriuretic peptide levels, echocardiographic parameters, and health-related quality of life (as assessed by the Kansas City Cardiomyopathy Questionnaire).
Ultimately, the Re-PHIRE study aims to determine if AZD3427 can improve key hemodynamic parameters—measures of blood flow and pressure directly linked to mortality in PH-LHD patients. The study’s findings are expected to guide AZD3427’s ongoing development for this patient population, particularly in identifying the phenotypes most likely to benefit from the treatment.
The design and rationale for the Re-PHIRE study were recently published in ESC Heart Failure. The CVC team is supporting study operations in Canada, with faculty leadership from Drs. Justin Ezekowitz and Jason Weatherald.
