A new class of antibiotics for systemic administration in humans

Discovered in 1950, pleuromutilins have the potential to be developed as a new class of antibiotics for systemic administration in humans. Although in 2007 retapamulin became the first pleuromutilin approved by the Food and Drug Administration (FDA) for topical use in humans, it was not until 2011 that a pleuromutilin antibiotic, Nabriva’s lefamulin, was tested successfully in a Phase 2 clinical trial for systemic administration in humans.

Nabriva's world class medicinal chemistry

In recent years, the effectiveness of many antibiotics has declined due to growing antibiotic resistance and cross-resistance (when bacterial strains become resistant to multiple classes of antibiotics). As a result, health-care providers have fewer options when treating serious infections. In 2010, the World Health Organization (WHO) stated that antibiotic resistance is one of the three greatest threats to human health.

Pleuromutilins inhibit bacterial growth by binding to a specific site on the bacterial ribosome that is responsible for bacterial protein synthesis. We have developed an understanding of how to optimize characteristics of the pleuromutilin class, such as antimicrobial spectrum, potency, absorption following oral administration and tolerability, which in turn led to our selection and development of lefamulin.


Lefamulin is a semi-synthetic compound that inhibits the synthesis of bacterial protein, which is required for bacteria to grow. Lefamulin acts by binding to the peptidyl transferase center, or PTC, on the bacterial ribosome in such a way that it interferes with the interaction of protein production at two key sites known as the “A” site and the “P” site, resulting in the inhibition of bacterial proteins and the cessation of bacterial growth. Lefamulin’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes.

We believe the preclinical studies and clinical trials we have conducted to date suggest that lefamulin’s novel mechanism of action is responsible for the lack of cross resistance observed with other antibiotic classes and may result in slow development of bacterial resistance to lefamulin over time. As a result of the favorable safety and tolerability profile we have observed in our clinical trials to date, we believe lefamulin will present fewer potential complications relative to the use of current therapies. Based on our research, we also believe that the availability of both intravenous (IV) and oral formulations of lefamulin, and an option to switch to oral treatment, could reduce the length of a patient’s hospital stay and the overall cost of care. Nabriva owns exclusive, worldwide rights to lefamulin.

Lefamulin is well suited for use as a first-line empiric monotherapy for the treatment of community-acquired bacterial pneumonia (CABP) because of its:

  • novel mechanism of action, with potential for slow development of bacterial resistance over time;
  • spectrum of activity against CABP pathogens, including against multi-drug resistant strains;
  • achievement of substantial drug concentrations in lung tissue and fluids;
  • availability as both an IV and oral formulation; and
  • favorable safety and tolerability profile.