Novartis has announced that acute heart failure drug serelaxin (RLX030) has failed to meet its primary endpoints in a phase 3 trial, casting doubts over the future of a drug once thought to be a strong candidate for blockbuster status. The Basel, Switzerland–based pharma harbored high hopes for the recombinant full-length human relaxin-2 hormone, following early results where serelaxin reduced deaths in people with acute heart failure by 37%, compared with conventional treatment. The outcomes of later trials were mixed, in part, it was thought, because of the difficulties in defining worsening heart failure. Then in 2014, both the US Food and Drug Administration and the European regulator rejected serelaxin. (Nat. Biotechnol. 32, 602–603, 2014), stating that the drug failed statistically to meet its primary endpoint of relief of dyspnea or shortness of breath in a single-arm trial. Novartis revised the trial design addressing the points that led to the rejection. Even so, in the latest study, a 6,600-patient phase 3 trial dubbed RELAX AHF-2, which evaluated serelaxin in addition to standard of care, the drug fell short of its primary endpoints of reducing cardiovascular death or ameliorating worsening heart failure. The rationale for looking at relaxin in heart failure was compelling: the hormone is produced by the ovaries and placenta during the normal course of pregnancy, to help remodel connective tissue for cervical ripening, as well as support physiological changes to accommodate the increased demands on the cardiovascular system. Following the most recent setback, Novartis has announced it will continue to analyze the data for serelaxin to learn from the results and determine its next steps.