This semi-synthetic compound inhibits the synthesis of bacterial protein, which is required for bacteria to grow. It 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. Its binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes.
We have completed the LEAP 1 Phase 3 trial evaluating the safety and efficacy of intravenous (IV) to oral lefamulin in adult patients with moderate to severe community-acquired bacterial pneumonia (CABP). In LEAP 1, our first clinical trial in patients with CABP, this regimen was compared to moxifloxacin (IV/oral). It met all primary FDA and EMA endpoints and was shown to be generally safe and well tolerated. LEAP 1 was a multi-center, randomized, controlled, double-blind, global study.
We are currently enrolling patients in the LEAP 2 Phase 3 trial, evaluating the efficacy and safety of oral lefamulin compared to oral moxifloxacin in subjects with moderate CABP. LEAP 2 is a multi-center, randomized, controlled, double-blind, global study. The company expects to complete enrollment in the fourth quarter of 2017, with initial data analysis to be completed in the spring of 2018. 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 over time. As a result of the favorable safety and tolerability profile we have observed in our clinical trials to date, we believe this antibiotic will present fewer potential complications relative to the use of current therapies.
Based on our research, we also believe that the availability of both 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. Based on a combined analysis of the U.S. Centers for Disease Control and Prevention’s 2007 National Ambulatory Medical Care Survey and 2013 data from the Healthcare Cost and Utilization Project, Nabriva Therapeutics estimates that more than 5 million adults visit a site of care for CABP treatment in the United States each year. Based on 2013 data from the Healthcare Cost and Utilization Project, Nabriva Therapeutics estimates that approximately 3 million of these adult CABP patients are diagnosed in a hospital setting, where most are then treated as in-patients with IV and oral antibiotics or as Transition of Care out-patients with oral antibiotics following hospital discharge or release.
Nabriva owns exclusive, worldwide rights to lefamulin.
We intend to further pursue the development of this antibiotic and are developing a formulation that is also appropriate for pediatric use. We believe that its product profile also provides the opportunity to expand to additional indications beyond pneumonia, such as the treatment of acute bacterial skin and skin structure infections (ABSSSI), sexually transmitted infections (STIs), ventilator-associated bacterial pneumonia (VABP), hospital-acquired bacterial pneumonia (HABP), osteomyelitis, and prosthetic joint infections.