Ularitide

Summary

Ularitide is a synthetic 32-amino acid natriuretic peptide identical to endogenous urodilatin, developed for the treatment of acute decompensated heart failure (ADHF). It promotes vasodilation and sodium/water excretion. Despite promising early-phase results, the Phase III TRUE-AHF trial (2017) failed to demonstrate a reduction in cardiovascular mortality compared to placebo, halting further clinical development.

Mechanism of Action

Synthetic analogue of urodilatin (a natriuretic peptide produced in the kidney); binds to natriuretic peptide receptors (NPR-A), activating guanylyl cyclase and increasing intracellular cGMP, leading to vasodilation, natriuresis, diuresis, and inhibition of the renin-angiotensin-aldosterone system (RAAS)

Routes of Administration

Goals & Uses

• Natriuresis and diuresisFluid/electrolyte ManagementModerate
• Acute decompensated heart failure treatmentCardiovascularModerate
• Systemic vasodilationHemodynamicModerate
• Reduction of cardiac filling pressuresHemodynamicModerate
• RAAS suppressionCardiovascular/EndocrineLow

Contraindications

• Systolic blood pressure < 90 mmHgHemodynamicHigh
• Cardiogenic shock or severe hypotensionCardiovascularHigh
• Severe renal impairment / anuriaRenalModerate
• Hypersensitivity to ularitide or natriuretic peptidesImmunologicalHigh

Adverse Effects

• HeadacheNeurologicCommonPain in the head or upper neck
• Atrial fibrillationCardiovascularUncommon
• HypotensionCardiovascularCommonLow blood pressure
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• Worsening renal functionRenalUncommon

Drug Interactions

• Phosphodiesterase inhibitors (e.g., sildenafil)High
• ACE inhibitors / ARBsModerate
• Antihypertensives / vasodilatorsModerate
• DiureticsLowMay worsen dehydration or electrolyte imbalance

Population Constraints

• Pediatric patientsAgeRelative
• Elderly patients (≥75 years)AgeRelative
• Pregnant womenReproductiveRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalInvestigated in EU clinical trials; no marketing authorization granted; development stopped
• United StatesInvestigationalInvestigated under IND for ADHF; not approved by FDA; development discontinued after TRUE-AHF failure
• United KingdomInvestigationalNo regulatory approval; follows EU precedent; not in active development

Not approved by FDA, EMA, or other major regulatory agencies. Development largely discontinued following negative Phase III (TRUE-AHF) results in 2017. Investigated under IND in the US and clinical trial authorization in the EU.

Evidence & Sources

No sources recorded yet.