Nearly 7 million people in the United States live with heart failure — and that incidence is expected to climb in the coming decades. LUMINARA, a new phase 2b clinical trial led by James Januzzi, MD, a cardiologist from the Mass General Brigham Heart and Vascular Institute and Baim Institute for Clinical Research, sheds light on the use of the investigational oral medication AZD5462, designed to improve cardiac remodeling and blood flow in patients with heart failure. The international, 375-patient clinical trial found that AZD5462 was well-tolerated and may benefit patients when paired with current standard of care therapies. The results are simultaneously published in Circulation and presented at the ESC Congress 2026 in Munich.
“Despite the progress that has been made and the benefits of current heart failure care, there are persistent unmet needs for these patients, and current treatments are often complicated by factors like low blood pressure or frequent medication and dosage tweaks,” said Januzzi. “New treatments are needed to improve patient experience and outcomes.”
AZD5462 is a drug developed by AstraZeneca, the trial’s sponsor. The drug exerts its effects by stimulating the relaxin family peptide receptor 1 (RXFP1). In preclinical studies, when scientists stimulated RXFP1, blood flow increased, and heart failure-related restructuring of heart shape and size reversed. These findings suggested that AZD5462 might have a benefit in patients with heart failure.
Januzzi and colleagues led the double-blind, placebo-controlled LUMINARA trial, which recruited 375 patients from 57 different centers spanning 10 countries. Participants were predominantly male and 65- to 70-years-old. All participants were diagnosed with chronic heart failure and randomized into one of four treatment groups — 20 mg, 80 mg, or 360 mg of AZD5462, or placebo — in which they took the dosages for 24 weeks in tandem with guideline-directed heart failure therapies.
At the 25-week check-in, AZD5462 was well-tolerated in all patients. Treatment with AZD5462 favorably reduced end-systolic volume index (the amount of blood left in a ventricle after the heart pumps), with the 20 mg dose leading to the biggest reduction. The researchers suggest that the lower dose provided enough benefit without triggering other effects — such as counter-regulatory hormone changes — that may come from higher doses. AZD5462 treatment also reduced systemic vascular resistance index, indicating the drug was an effective vasodilator.
“The findings support AZD5462’s safety and efficacy, and illuminate a path forward for targeting RXFP1 for treating heart failure,” said Januzzi. “Future research in larger studies is now needed to determine long-term benefits of oral relaxin therapy in heart failure.”
AZD5462 is an investigational medicine and is not approved by the FDA or any other regulatory body.
Authorship: In addition to Januzzi, authors include Jaya B. Rosenmeier, Patricia Ely Pizzato, Macarena P. Quintana-Hayashi, Lai-Shan Melanie Chan, Petra Johannesson, Chandrali S. Bhattacharya, Daniel Aradi, Jeroen Schaap, Jiri Vesely, Grzegorz Piotrowski, Koichiro Kinugawa, Daniel Pettersen, Joao Lima, Martin Fredriksson, for the LUMINARA Investigators.
Disclosures : Januzzi has received research grants with Abbott Diagnostics, Applied Therapeutics, AstraZeneca, Bristol Myers Squibb, HeartFlow, and Novartis; has acted as a consultant, advisor, or speaker for Abbott, AstraZeneca, Bayer, Beckman Coulter, Boehringer Ingelheim, BridgeBio, Bristol Myers Squibb, Intellia Therapeutics, Merck, Moderna, Novartis, Pfizer, Roche Diagnostics, and Siemens; and has equity in Fibrosys, Imbria Pharmaceuticals, Jana Care, and Prevencio. Aradi has received lecture fees from Amgen, AstraZeneca, Bayer, Boehringer, Krka, Novartis, Novo Nordisk and Pfizer. Schaap has received sponsorship/research funding from Boehringer Ingelheim, Astra Zeneca, Novo Nordisk and Pharma Nord; and service fee from Boehringer Ingelheim, Daiichi Sankyo, AstraZeneca, General Electric, Novo Nordisk, Eli Lilly and Novartis. Kinugawa has received consultation fees from Otsuka, Abiomed, Novartis, Medtronic, Boehringer Ingelheim, Abbott and Bayer; renumeration for lectures from Otsuka, Abiomed, Novartis, Medtronic, Boehringer Ingelheim, Abbott, Daiichi-Sankyo, Alnylam, Nipro, AstraZeneca, Ono and Bayer; manuscript fees from Otsuka; trust research/joint research funds from Ono, Kowa and Boehringer Ingelheim; and scholarship fund from Otsuka and Ono. Vesely has received lecture fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier, Pfizer, and served as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, and Eli Lily. Lima has received grant support from AstraZeneca and Canon Medical Systems. Rosenmeier is now an employee of Novartis. Pizzato, Quintana-Hayashi, Chan, Johannesson, Bhattacharya, and Fredriksson are employees and stockholders of AstraZeneca .
Funding: The LUMINARA trial was funded by AstraZeneca.
Paper cited: Januzzi J et al. “Oral Relaxin Receptor Agonist AZD5462 in Participants with Chronic Heart Failure: Primary Results from the LUMINARA Trial” Circulation DOI: xxx
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Circulation
Randomized controlled/clinical trial
People
Oral Relaxin Receptor Agonist AZD5462 in Participants with Chronic Heart Failure: Primary Results from the LUMINARA Trial
30-Aug-2026
Januzzi has received research grants with Abbott Diagnostics, Applied Therapeutics, AstraZeneca, Bristol Myers Squibb, HeartFlow, and Novartis; has acted as a consultant, advisor, or speaker for Abbott, AstraZeneca, Bayer, Beckman Coulter, Boehringer Ingelheim, BridgeBio, Bristol Myers Squibb, Intellia Therapeutics, Merck, Moderna, Novartis, Pfizer, Roche Diagnostics, and Siemens; and has equity in Fibrosys, Imbria Pharmaceuticals, Jana Care, and Prevencio. Aradi has received lecture fees from Amgen, AstraZeneca, Bayer, Boehringer, Krka, Novartis, Novo Nordisk and Pfizer. Schaap has received sponsorship/research funding from Boehringer Ingelheim, Astra Zeneca, Novo Nordisk and Pharma Nord; and service fee from Boehringer Ingelheim, Daiichi Sankyo, AstraZeneca, General Electric, Novo Nordisk, Eli Lilly and Novartis. Kinugawa has received consultation fees from Otsuka, Abiomed, Novartis, Medtronic, Boehringer Ingelheim, Abbott and Bayer; renumeration for lectures from Otsuka, Abiomed, Novartis, Medtronic, Boehringer Ingelheim, Abbott, Daiichi-Sankyo, Alnylam, Nipro, AstraZeneca, Ono and Bayer; manuscript fees from Otsuka; trust research/joint research funds from Ono, Kowa and Boehringer Ingelheim; and scholarship fund from Otsuka and Ono. Vesely has received lecture fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier, Pfizer, and served as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, and Eli Lily. Lima has received grant support from AstraZeneca and Canon Medical Systems. Rosenmeier is now an employee of Novartis. Pizzato, Quintana-Hayashi, Chan, Johannesson, Bhattacharya, and Fredriksson are employees and stockholders of AstraZeneca.