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Ularitide

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 17 September 2026

Ularitide is a synthetic form of urodilatin, a real natriuretic peptide, tested in a large, well-designed trial for acute heart failure — and it failed cleanly on both co-primary endpoints, never reaching approval anywhere, making it the most decisive negative result among the natriuretic-peptide drugs this site covers.

On this page
  1. What it is
  2. TRUE-AHF: a clean, negative result
  3. Why this failure matters

In brief

Should you care? This drug was never approved and isn't available — it's here as a case study in a well-run trial that cleanly failed.

The short version

  • A synthetic form of urodilatin, a real kidney-derived natriuretic peptide related to ANP.
  • TRUE-AHF (2,157 patients): missed both co-primary endpoints — no reduction in cardiovascular mortality, no improvement in the clinical composite outcome.
  • A cleaner failure than most — large, well-designed, placebo-controlled, and unambiguous, unlike some approved drugs on this site with murkier evidence.

What it is

Ularitide is a synthetic 32-amino-acid peptide identical to human urodilatin — a natriuretic peptide made directly in the kidney tubules, structurally related to ANP but resistant to the enzyme that normally breaks such peptides down, giving it natriuretic, diuretic, and vasodilatory effects. It was developed by the Swiss company Cardiorentis for acute heart failure and received FDA Fast Track designation, but was never approved anywhere.

TRUE-AHF: a clean, negative result

The pivotal trial, TRUE-AHF (Packer et al., N Engl J Med 2017, PMID 28402745), was large and well-designed: 2,157 patients with acute heart failure, randomized to 48-hour IV ularitide or placebo added to standard care. It had two co-primary endpoints, and missed both. Long-term cardiovascular mortality: 21.7% with ularitide versus 21.0% with placebo (hazard ratio 1.03, 95% CI 0.85-1.25, p=0.75) — no benefit at all. The hierarchical clinical composite endpoint during the hospital stay also showed no significant difference between groups — this despite ularitide producing real, measurable short-term physiologic improvements (lower blood pressure, lower NT-proBNP) that simply didn't translate into any better outcome that mattered.

Why this failure matters

Compare this to nesiritide elsewhere on this site, which was approved on symptom relief and only later, in a large post-approval trial, found not to move harder outcomes like mortality or rehospitalization. Ularitide never got that far — its own large, placebo-controlled trial closed the question before an approval ever happened. It's arguably the more decisive, easier-to-interpret negative result of the two: a real drug, tested honestly, that simply didn't work for the outcomes that matter most.

References

  1. Packer M, Holcomb R, Abraham WT, et al. (TRUE-AHF Investigators), "Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure," N Engl J Med 2017;376(20):1956-1964, PMID 28402745, DOI: 10.1056/NEJMoa1601895.