Murepavadin

Summary

Murepavadin (formerly POL7080) is a first-in-class cyclic β-hairpin peptidomimetic antibiotic with selective, potent activity against Pseudomonas aeruginosa, including multidrug-resistant (MDR) strains. It targets LptD, a novel and validated antibacterial target, representing a completely new mechanism of action. Clinical development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) was placed on clinical hold by the FDA in 2019 due to safety concerns (nephrotoxicity) observed in combination therapy trials.

Mechanism of Action

Selectively inhibits LptD (lipopolysaccharide transport protein D), a β-barrel outer membrane protein essential for lipopolysaccharide (LPS) transport to the outer leaflet of the Gram-negative outer membrane, disrupting outer membrane biogenesis and causing bacterial cell death in Pseudomonas aeruginosa.

Routes of Administration

Goals & Uses

• Treatment of MDR/XDR Pseudomonas aeruginosa infectionsAntibacterial Therapy – Resistant PathogensModerate
• Inhaled therapy for pulmonary P. aeruginosa (e.g., cystic fibrosis)Infectious Disease / PulmonaryLow
• Ventilator-associated bacterial pneumonia (VABP)Infectious Disease / Critical CareModerate
• Hospital-acquired bacterial pneumonia (HABP)Infectious Disease / PulmonaryModerate
• Treatment of Pseudomonas aeruginosa infectionsAntibacterial TherapyModerate

Contraindications

• Known hypersensitivity to murepavadin or peptidomimetic componentsAllergy/ImmunologyHigh
• Severe pre-existing renal impairmentRenalHigh
• Concurrent use of nephrotoxic agentsDrug Interaction / RenalHigh

Adverse Effects

• Acute kidney injury / NephrotoxicityRenalUncommon
• HeadacheNeurologicCommonPain in the head or upper neck
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• Elevated serum creatinineRenal / LaboratoryUncommon
• Infusion-related reactionsHypersensitivityCommon

Drug Interactions

• Aminoglycosides (e.g., tobramycin, amikacin)High
• VancomycinHigh
• NSAIDsModerateMay increase renal risk in susceptible patients
• Colistin / Polymyxin BHigh

Population Constraints

• Patients with pre-existing renal impairmentOrgan FunctionRelative
• Pediatric patientsAgeRelative
• Pregnant or breastfeeding womenReproductiveRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionInvestigationalNot approved. Developed by Polyphor AG (Switzerland); clinical development paused following Phase III safety concerns.
• United StatesInvestigationalFDA placed Phase III trials on clinical hold in 2019 due to nephrotoxicity signals. No approved indications. Qualified Infectious Disease Product (QIDP) designation and Fast Track designation previously granted.
• United KingdomInvestigationalNot approved in the UK. Status mirrors EU investigational classification.

FDA placed Phase III clinical trials on clinical hold in 2019 following reports of serious renal adverse events (acute kidney injury) in patients receiving murepavadin in combination with standard-of-care antibiotics. Development was paused; inhaled formulation strategies have been explored to potentially reduce systemic exposure and nephrotoxicity.

Evidence & Sources

No sources recorded yet.