AZD5462 shows promise in phase 2b heart-failure trial

At the 25-week check-in, the signal was visible in the numbers: patients taking AstraZeneca’s investigational oral drug AZD5462 had lower end-systolic volume index, the amount of blood left in a ventricle after the heart pumps. The result came from the 375-patient phase 2b LUMINARA trial, whose findings were presented at ESC Congress 2026 in Munich and published in Circulation.

Led by cardiologist James Januzzi of Mass General Brigham Heart and Vascular Institute and the Baim Institute for Clinical Research, the double-blind, placebo-controlled study recruited patients from 57 centers in 10 countries. Participants, predominantly men aged 65 to 70, took 20 mg, 80 mg or 360 mg of AZD5462—or placebo—for 24 weeks, alongside guideline-directed heart-failure therapies.

The 20 mg dose produced the biggest reduction in end-systolic volume index. Researchers suggested that the lower dose delivered enough benefit without triggering other effects, including counter-regulatory hormone changes, that may occur at higher doses. Treatment also reduced systemic vascular resistance index, indicating that AZD5462 acted as a vasodilator, widening blood vessels.

AZD5462 stimulates RXFP1, the relaxin family peptide receptor 1. In preclinical studies, activating RXFP1 increased blood flow and reversed heart-failure-related restructuring of the heart’s shape and size. Fierce Biotech described the phase 2b results as encouraging across measures of cardiac function in chronic heart failure.

For patients, the near-term change is limited but concrete: an oral medicine that was well tolerated in this trial could eventually add another option to existing heart-failure treatment. That possibility remains unproven beyond the study’s 25-week check-in: AZD5462 is not approved by the FDA or any other regulatory body, and larger studies must establish whether the measured improvements translate into durable clinical benefits.