AstraZeneca executives have told Fierce Biotech they still see potential in harnessing the relaxin hormone to treat heart failure despite abandoning work on one of two clinical-stage candidates.
As part of its full-year 2025 financial results (PDF), the U.K.-based Big Pharma revealed that it removed a long-acting relaxin-2 analog called AZD3427 from its pipeline, citing underwhelming efficacy in a phase 2 trial.
There is a history of studying relaxin in cardiovascular settings—Novartis started a phase 3 heart failure trial of a recombinant relaxin-2 peptide in 2013—but preclinical evidence of the molecule’s vasodilatory, anti‐inflammatory and antifibrotic effects has yet to translate into clinical success.
AstraZeneca identified the short half-lives of earlier candidates as a potential cause of the failures. To fix the problem, the company created a relaxin-2 mimic fusion protein and attached a fragment to create a candidate with a half-life measured in days rather than hours.
However, AstraZeneca has now stopped development of AZD3427 after completing a phase 2 trial in 260 people with heart failure.
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While AZD3427 has been sunk by efficacy, the company is continuing to develop the oral relaxin drug candidate AZD5462. AstraZeneca has called (PDF) the candidate the first small molecule targeting relaxin biology to enter clinical trials. Data from a phase 2b trial of stable patients with chronic heart failure are due in the second half of 2026.
During a press conference this morning, Sharon Barr, Ph.D., executive vice president of biopharmaceuticals R&D at AstraZeneca, told Fierce the company is moving forward with AZD5462 “because we think this is a potentially important molecule.”
“One of the things that we have learned from competitor studies is that dosing matters,” Barr continued. “You really have to find that perfect space between efficacy and congestion, and we think we’ve put in the hard yards to really understand the posology there, and we’re moving forward with our existing program.”
AstraZeneca CEO Pascal Soriot also told Fierce during the call that work on the relaxin program is a case study of “what is so exciting in this industry at this present time.”
Soriot pointed to the likes of ACE inhibitors and SGLT2 drugs as examples of the progress made in recent years to treat specific groups of cardiovascular patients.
“There’s more and more of those technologies, and we need just to pick the right products to really help patients with heart disease,” the CEO added.
AstraZeneca disclosed its discontinuation of AZD3427 alongside the removal of two other new molecular entities from the pipeline. The drugmaker confirmed the removal of AZD0233, a CX3CR1 modulator that was in development as a treatment for dilated cardiomyopathy. AstraZeneca terminated a phase 1 trial of the candidate last month over an adverse finding in a nonclinical, chronic toxicology study.
The company also revealed it had axed a COVID-19 vaccine program. AstraZeneca moved the mRNA viruslike particle vaccine program into phase 1 in late 2023. Recently, the company reported that a vaccine candidate was well tolerated compared to Pfizer and BioNTech’s Comirnaty and generated similar immunogenicity at one-third of the dosage.