Overview

Friulimicin is the first-in-class compound of a novel class lipopeptide antibiotics with a unique, highly specific mode of action. By inhibiting the late stage bacterial cell wall biosynthesis friulimicin displays broad spectrum activity against Gram-positive bacteria, including multi-resistant pathogens.

Friulimicin consists of a macrocyclic decapeptide core and a lipid tail attached to an exocyclic amino acid. Friulimicin is amphiphilic and highly water soluble, allowing easy administration to livestock through drinking water.

 

Structure of friulimicin

Mode of action

The general effectiveness of cell wall biosynthesis inhibition has already been successfully established by antibiotics like vancomycin, the carbapenems or cephalosporins. However, friulimicin has a completely different mode of action than these well-established drugs by forming a complex with the bactoprenol phosphate carrier C55-P. By binding to C55-P friulimicin blocks two target areas of cell wall biosynthesis reactions: The peptidoglycan biosynthesis and the teichoic acid biosynthesis.

The simultaneous interference with these pathways obstructs the formation of a functional cell wall in Gram-positive bacteria and thereby kills these bacteria efficiently. There is no antibiotic in current use that shares this activity.

A new animal health antibiotic

Friulimicin has proven its activity in several animal models with good tolerability. However, it cannot be used in humans due to primate-specific side effects. Thus, friulimicin represents a unique opportunity for a new animal health antibiotic, by its overall substance characteristics and in that it would represent a specific class of compounds exclusively used in animals; any concerns and potential issues of a massive, parallel utilization of the same drug in animals and humans due to the potential formation of cross-resistances and thereby subsequently limiting the effectiveness of these antibiotics in humans would be avoided.

 

The advantages of friulimicin

    Friulimicin
  Competitors
Mode of action   Inhibition of two independent bacterial cell wall synthesis pathways by a novel mode of action differing from all antibiotics currently in use   With few exceptions same targets are addressed by other members of the drug class
Microbiological spectrum   Broad coverage of gram-positive pathogens; excellent activity against anaerobes   Limitations due to resistance in nearly all bacterial species because of use since decades
Resistance   Breaks the resistance mechanisms against all currently used antibiotics; slow development of resistance against friulimicin detected in vitro   Usually facing growing resistance levels; quicker resistance development due to re-existing primed mutants in the pathogen population
PK/PD   Long lasting kinetics in various animal species; no significant systemic exposure after oral dosing, thus delivering high drug concentrations to the gut   Various PK profiles
Safety   Good tolerability for all animals except primates; use in humans not possible due to species-specific hemolytic side effect of drug class   Various tox profiles
Use in humans   Novel lipopeptide; no other member of this drug class is under development or currently used in humans or animals   The overwhelming number of currently used and newly registered veterinary antibiotic products are generic and also used for humans