AstraZeneca’s AZD5462 revives interest in relaxin-based heart-failure treatment

At ESC Congress 2026, AstraZeneca reported Phase IIb LUMINARA results for AZD5462, an investigational once-daily oral agonist of the relaxin receptor RXFP1.

In patients with heart failure and reduced ejection fraction (LVEF ≤35%), the lowest dose produced the strongest signal, reducing left-ventricular end-systolic volume index by 5.4 mL/m² versus baseline at 24 weeks; the comparison with placebo narrowly missed conventional statistical significance (p=0.054).

Among patients with mildly reduced or preserved-range EF (LVEF 41–55%), AZD5462 reduced systemic vascular resistance by 15%–21%, indicating vasodilatory target engagement.

The drug was generally well tolerated. Mild blood-pressure lowering occurred, but significant hypotension was no more common than with placebo, and investigators reported no signal of the problematic fluid retention associated with earlier relaxin-like therapies.

The findings revive interest in relaxin biology after previous disappointments, but they are mechanistic, mid-stage results—not proof that AZD5462 reduces deaths or hospitalizations. Larger Phase III outcome trials are needed, and the medicine is not approved by regulators.