Murepavadin: a new antibiotic class in the pipeline

ABSTRACT

Introduction: With the increase in multi-drug resistant P. aeruginosa, antimicrobials with a novel mechanism of action are needed that can target these infections.

Areas covered: Intravenous murepavadin is in Phase 3 development for the treatment of HABP/VABP due to P. aeruginosa. This paper summarizes the available information on the discovery, the in vitro activity, pharmacokinetic and pharmacodynamic properties and the clinical pharmacology of murepavadin to date.

Expert commentary: P. aeruginosa has an intrinsic resistance to many antibiotics due to high cellular impermeability and efficient drug efflux mechanisms, and the recent increase in prevalence of multidrug-resistant P. aeruginosa infections are particularly threatening in ICU settings. Murepavadin is a pathogen specific antimicrobial peptidomimetic with a novel, non-lytic mechanism of action, and is the first in class of outer membrane protein targeting antibiotics which are being developed. Murepavadin displays a potent in vitro activity including carbapenemase-producing and colistin-resistant P. aeruginosa. Murepavadin is active in pre-clinical animal models including infections with XDR isolates. The Pharmacokinetics is well characterized including subjects with impaired renal function and patients with VABP. Intravenous murepavadin is currently under clinical development for the treatment of HABP/VABP due to P. aeruginosa infection.

KEYWORDS:

• Sepsis
• pneumonia
• VAP
• HAP
• pseudomonas
• p. aeruginosa
• antibiotic
• resistance
• MDR

Declaration of interest

Martin-Loeches and A. Torres acted as clinical advisors to Polyphor. G.E Dale is an employee of Polyphor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed participation as a principle investigator in one phase II trial of POL7080, another reviewer has disclosed previous work with Roche during development of the compound and consulted on the human intrapulmonary penetration study.

Additional information

Funding

The manuscript was funded by Polyphor Ltd, Allschwil, Switzerland