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

[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.
[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.
[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.

Quick facts

Class

A chemically synthesized version of urodilatin — a 32-residue natriuretic peptide produced in the kidney by post-translational modification of the proANP precursor (four additional N-terminal residues compared with circulating ANP). Developed by Cardiorentis as an IV treatment for acute decompensated heart failure; TRUE-AHF Phase 3 trial (n=2,157, NEJM 2017) failed to meet either of its co-primary endpoints. Development discontinued.

Subcategory

Natriuretic peptide — guanylate cyclase-A (NPR-A) agonist

Sequence

TAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY (32 residues; disulfide bond Cys11-Cys27; the 4-residue TAPR- N-terminal extension is the kidney-processed signature)

Molecular formula

C144H229N51O43S3

Molecular weight

3508.99 Da

Half-life

~13 minutes (mean) — Extended compared with ANP (3 minutes) due to the N-terminal extension resisting neprilysin cleavage. Still requires continuous IV infusion for clinical use.

Evidence level

High

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.