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Getting the latest healthcare news for you
A new once-daily pill for heart failure is turning heads. AZD5462, the first oral RXFP1 agonist, demonstrated favorable hemodynamic effects and a solid safety profile in the phase 2b LUMINARA trial across patients with both reduced and mildly reduced ejection fractions. Researchers say the 20 mg dose looks like the one to watch in future trials.
A new once-daily pill for heart failure is turning heads.
Presented at the European Society of Cardiology Congress and published in Circulation, the phase 2b LUMINARA trial evaluated AZD5462 — the first oral once-daily relaxin family peptide receptor 1 (RXFP1) agonist — in 375 heart failure patients spanning the ejection fraction spectrum. Previous drugs targeting this receptor were only given intravenously, limiting their long-term use. AZD5462 works by reducing systemic vascular resistance, improving organ perfusion, and promoting reverse cardiac remodeling.
The trial split patients into two cohorts: those with reduced ejection fraction (LVEF ≤35%) and those with mildly reduced ejection fraction (LVEF 41–55%). In the mildly reduced group, all three doses hit the primary endpoint of lowering systemic vascular resistance. In the reduced ejection fraction group, the lower doses trended toward benefit, with the 20 mg dose performing best — likely because higher doses triggered a compensatory rise in renin levels.
By the Numbers:
Why it matters: Heart failure remains notoriously hard to treat, especially across different ejection fraction subtypes. An oral, once-daily option that works broadly — and is well tolerated on top of standard therapies — could be a meaningful step forward. Researchers are moving ahead with the 20 mg dose for further development.
