Skip to content
Discontinued Cardiovascular & Renal

Ularitide

also known as: Urodilatin, INN-00835, URO-7, chemically synthesized urodilatin

⚠ Phase 3 failure. Cardiorentis's ularitide was the most recent Western attempt to develop an IV natriuretic peptide for acute heart failure. TRUE-AHF (NEJM 2017, n=2,157) failed both the mortality and hemodynamic co-primary endpoints; development was discontinued shortly after. Reinforced a now-consistent pattern of IV natriuretic peptides showing biochemical and hemodynamic effects but failing to improve clinical outcomes.

A synthetic 32-residue natriuretic peptide identical to endogenous urodilatin — the kidney-specific processed form of proANP that contains the 28-residue ANP sequence plus four additional N-terminal residues (T-A-P-R-) that provide substantial resistance to neprilysin degradation. Developed by Cardiorentis (subsidiary of Daiichi Sankyo at one stage) as an IV therapy for acute decompensated heart failure. The pivotal TRUE-AHF trial (Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure; Packer et al, NEJM 2017; n=2,157) randomised acute HF patients to 48-hour ularitide infusion or placebo and failed on both co-primary endpoints — short-term clinical composite (hierarchical) and cardiovascular mortality through end of follow-up. Development was effectively discontinued following this readout.

Mechanism of action

Agonist at natriuretic peptide receptor A (NPR-A / GC-A) — mechanistically identical to ANP and nesiritide. Hypothesised clinical advantage in heart failure was a higher ratio of renal to peripheral effect versus ANP / BNP (greater natriuresis relative to vasodilation) and the resistance to neprilysin degradation conferred by the TAPR- N-terminal extension. Despite acute hemodynamic improvements (reduced NT-proBNP, reduced diastolic BP, reduced pulmonary congestion), TRUE-AHF showed no impact on the hierarchical clinical composite or on cardiovascular mortality through follow-up (median 15 months).

Primary uses

  • ⚠ Investigational (discontinued). Evaluated for acute decompensated heart failure in TRUE-AHF Phase 3 trial; failed both co-primary endpoints. No current indication.

Typical dosing

15 ng/kg/min for 48 hours (TRUE-AHF dosing regimen) continuous 48-hour IV infusion (intravenous)

⚠ Investigational dosing only. TRUE-AHF used a fixed 48-hour infusion at 15 ng/kg/min. Drug has never been commercially available.

Regulatory status

Not FDA-approved. Not approved in any jurisdiction. Pivotal TRUE-AHF Phase 3 trial failed both co-primary endpoints (NEJM 2017). Cardiorentis wound down the development program following the TRUE-AHF readout. No active program identified as of 2026.

References

  1. [clinical-trial] Packer M, O'Connor C, McMurray JJV, et al. "Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF)." N Engl J Med, 2017;376(20):1956-1964.
  2. [pubmed] Mitrovic V, Luss H, Nitsche K, et al. "Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial." Am Heart J, 2005;150(6):1239.
  3. [review] Vesely DL. "Natriuretic peptides: discovery, current role in cardiovascular therapeutics, and future uses." Cardiovasc Hematol Disord Drug Targets, 2013;13(2):109-123.

Related peptides

Nesiritide

Natrecor — the first recombinant natriuretic peptide drug for acute heart failure. FDA-approved August 2001 based on short-term dyspnea relief, became one of the most controversial drugs of the 2000s after 2005 meta-analyses raised safety concerns; ASCEND-HF (2010, n=7,141) eventually settled the safety debate but demonstrated only marginal clinical benefit. Janssen discontinued manufacturing February 2018; no longer commercially available in the US.

Carperitide

⚠ Approved in Japan only (1995). The Daiichi Sankyo recombinant hANP has been used in >30,000 pooled patients with acute heart failure in Japanese registries, but its overall mortality effect remains contested — 2024 meta-analyses suggest a possible increase in in-hospital mortality, while other pooled analyses suggest benefit at low doses.

Guides & tools

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.