Serelaxin

Serelaxin is a recombinant form of human relaxin-2, a real hormone your body makes during pregnancy, developed by Novartis as an infusion for acute heart failure. Its first Phase 3 trial found a striking reduction in death at six months — enough that an FDA advisory committee still voted 11-0 against approval in 2014 over concerns that a single trial, on a soft primary endpoint, wasn't enough. Novartis ran a second, larger confirmatory trial to settle the question. It found no benefit at all. Development was discontinued in 2017, and no country has ever approved serelaxin.

A pregnancy hormone, repurposed for a hospital emergency

Relaxin-2 is a real, naturally occurring human peptide hormone — 53 amino acids across two chains, structurally related to insulin and IGF-1 — produced in large quantities by the corpus luteum during pregnancy, where it helps relax connective tissue and dilate blood vessels. Researchers noticed its vasodilatory, anti-fibrotic and cardioprotective effects in animal and early human studies and began investigating a recombinant version, serelaxin (RLX030), as an infused drug for acute heart failure: the idea that its blood-vessel-relaxing and organ-protective effects, given intravenously over 48 hours during a hospital admission, might reduce the strain on a failing heart and protect the kidneys and liver from the congestion that acute heart failure causes. Corthera, a small biotech, developed serelaxin through Phase 2; Novartis acquired Corthera for roughly $120 million upfront in December 2009 specifically for the molecule, with up to $500 million more in potential milestones, and ran it through Phase 3.

RELAX-AHF: a real trial, a striking mortality signal, and a vote against it anyway

The pivotal Phase 3 RELAX-AHF trial randomized 1,161 patients hospitalized for acute heart failure to a 48-hour serelaxin infusion or placebo, added to standard care. Its primary endpoint — improvement in patient-reported breathlessness over the first several days — was met on one of its two pre-specified statistical measures but not the other, a genuinely mixed primary result. What drew far more attention was a secondary, exploratory finding: death from cardiovascular causes or any cause through day 180 was reduced by 37% in the serelaxin group (Teerlink JR, Cotter G, Davison BA, et al., "Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial," Lancet 2013;381(9860):29-39, PMID 23141816, DOI: 10.1016/S0140-6736(12)61855-8).¹ A 37% mortality reduction in a hospitalized heart-failure population, if real, would be a genuinely major result — which is exactly why regulators treated it with real caution rather than as settled fact.

Why the FDA's advisory committee said no

This is a genuinely different story from most of this site's discontinued-drug pages, where a safety signal or a missed primary endpoint sank an otherwise-working drug. Here, the drug's own headline result — a large mortality reduction — was exactly what the advisory committee didn't yet trust, on the reasoning that a single trial's secondary finding needed independent confirmation before being relied on for a life-or-death indication. Novartis agreed, at least in the sense of running the confirmatory trial the FDA was effectively asking for.

RELAX-AHF-2: the confirmatory trial that ended it

RELAX-AHF-2 was a much larger, purpose-built confirmatory trial: 6,545 patients hospitalized for acute heart failure, randomized to the same 48-hour serelaxin infusion or placebo, with two co-primary endpoints chosen specifically to test the mortality signal directly — cardiovascular death by day 180, and worsening heart failure by day 5. Serelaxin missed both. Cardiovascular death occurred in 8.7% of the serelaxin group versus 8.9% on placebo (hazard ratio 0.98, 95% CI 0.83-1.15; p=0.77); worsening heart failure at day 5 occurred in 6.9% versus 7.7% (hazard ratio 0.89, 95% CI 0.75-1.07; p=0.19) (Teerlink JR, Voors AA, Ponikowski P, et al., "Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study," and the primary results paper, Metra M, Teerlink JR, Cotter G, et al., "Effects of Serelaxin in Patients with Acute Heart Failure," N Engl J Med 2019;381(8):716-726, PMID 31433919, DOI: 10.1056/NEJMoa1801291).² The confirmatory trial the advisory committee had effectively asked for came back negative on the exact question it was designed to answer. Novartis announced in March 2017, before the trial had even fully read out its results, that it was closing out serelaxin's remaining ongoing studies early and discontinuing the acute-heart-failure program.

Current status

Serelaxin has never been approved anywhere, and no company is developing it for acute heart failure today. It is not a live grey-market or research-chemical product in the way some other unapproved peptides on this site are — its cost and complexity of manufacture (recombinant E. coli production, hospital-only IV infusion) put it well outside that market entirely. The underlying biological target has not been fully abandoned: other companies have since tested newer, differently engineered molecules at the same relaxin receptor (RXFP1) in early-stage heart-failure trials, but those are distinct molecules from serelaxin itself, at an earlier and unproven stage, not a revival of this specific drug.