AstraZeneca’s experimental drug AZD5462 showed promise in a mid-stage trial for chronic heart failure, with results presented at the European Society of Cardiology meeting in Munich. The oral treatment targets the relaxin pathway, improving cardiac function in two patient groups with different disease severity levels.
The LUMINERA trial enrolled 375 patients, divided into two cohorts based on left ventricular ejection fraction (LVEF), a measure of the heart’s pumping ability. One group had severely reduced LVEF (35% or less), while the other had mildly to moderately reduced function (between 41% and 55%). All patients maintained stable, maximally tolerated standard-of-care therapies throughout the study.
Researchers tested three doses of AZD5462 against placebo over 24 weeks. The drug acts as a selective agonist of the relaxin family peptide receptor 1, mimicking the body’s natural relaxin hormone, which aids cardiovascular adaptation during pregnancy.
Impact on Severe Heart Failure
In patients with severely reduced LVEF, the lowest dose of AZD5462 demonstrated the most beneficial effects. End systolic volume index—a marker of adverse cardiac remodeling—decreased by 5.4 milliliters per square meter from baseline at week 24. Changes in ejection fraction itself also showed the strongest response at this dose level.
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The primary endpoint for this group was the change in end systolic volume index from study start to week 24. Greater reductions in this measurement indicate reverse remodeling of the heart, a key goal in heart failure treatment.
Effects on Mild to Moderate Heart Failure
Among patients with mildly to moderately reduced LVEF, AZD5462 reduced systemic vascular resistance at all dose levels. The 20-milligram dose lowered resistance by 19%, while the 80-milligram and 360-milligram doses achieved 21% and 15% reductions, respectively, at 24 weeks. The primary endpoint for this cohort was the change in systemic vascular resistance index from baseline.
The drug was generally well tolerated. Adverse events remained low, with only mild blood pressure reductions, and no significant increase in hypotension compared to placebo. This addresses previous concerns about side effects when targeting the relaxin pathway.
The Need for New Treatments
Despite available therapies, many heart failure patients still face substantial disease burden. Professor James Januzzi, a trial investigator, highlighted the ongoing challenge of treating this population.
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“Relaxin, a pregnancy peptide hormone, has potential benefits for heart failure patients,” Januzzi said. “Earlier attempts to develop relaxin receptor-targeting drugs faced challenges, but data from preclinical and early clinical studies with AZD5462 have been promising.”
Previous relaxin pathway research encountered setbacks. Both Eli Lilly and AstraZeneca discontinued their respective drugs, volenrelaxin and AZD3427, due to issues in development. Earlier studies noted an absence of significant volume overload seen with higher doses of relaxin-like compounds.
Market analysts expect the heart failure treatment space to grow. GlobalData projects the market to expand from $13.5 billion in 2022 to $33.9 billion in 2032 across key markets. Established therapies like Jardiance, Inpefa, and Entresto are expected to drive much of this growth.
