Eravacycline
 

Eravacycline

We are developing our lead product candidate, eravacycline, as a broad-spectrum intravenous and oral antibiotic for the treatment of multidrug-resistant (MDR) infections, including those caused by MDR Gram-negative bacteria. We are currently investigating the safety and efficacy of eravacycline in a Phase 3 program called IGNITE (Investigating Gram-negative Infections Treated with Eravacycline) for the treatment of complicated intra-abdominal infections (cIAI)(IGNITE 1) and complicated urinary tract infections (cUTI)(IGNITE 2). With top-line data from both studies expected by mid-year 2015, we expect to be able to file for U.S. regulatory approval for eravacycline for both indications by the end of 2015.

Eravacycline is a novel, fully synthetic tetracycline antibiotic. We selected eravacycline for development from tetracycline derivatives that we generated using our proprietary chemistry technology on the basis of the following characteristics of the compound that we observed in in vitro studies of the compound:

  • potent antibacterial activity against a broad spectrum of susceptible and multi-drug resistant bacteria, including Gram-negative, Gram-positive, atypical and anaerobic bacteria;
  • potential to treat the majority of patients as a first-line empiric monotherapy with convenient dosing; and
  • potential for intravenous-to-oral step-down therapy.

In in vitro studies, eravacycline has been highly active against emerging MDR pathogens like Acinetobacter baumannii as well as clinically important species of Enterobacteriaceae, including those isolates that produce ESBLs or that are resistant to the carbapenem class of antibiotics, and anaerobes.

Based on in vitro studies we have completed, eravacycline shares a similar potency profile with carbapenems except that it more broadly covers Gram-positive pathogens like MRSA and enterococci, is active against carbapenem-resistant Gram-negative bacteria and unlike carbapenems like Primaxin and Merrem is not active against Pseudomanas aeruginosa. Eravacycline has demonstrated strong activity in vitro against Gram-positive pathogens, including both nosocomial and community-acquired methicillin susceptible or resistant Staphylococcus aureus strains, vancomycin susceptible or resistant Enterococcus faecium and Enterococcus faecalis, and penicillin susceptible or resistant strains of Streptococcus pneumoniae. In in vitro studies for cIAI, eravacycline consistently exhibited strong activity against enterococci and streptococci. One of the most frequently isolated anaerobic pathogens in cIAI, either as the sole pathogen or often in conjunction with another Gram-negative bacterium, is Bacteroides fragilis. In these studies eravacycline demonstrated activity against Bacteroides fragilis and a wide range of Gram-positive and Gram-negative anaerobes.

Key Differentiating Attributes of Eravacycline
The following key attributes of eravacycline, observed in clinical trials and preclinical studies of eravacycline, differentiate eravacycline from other antibiotics targeting MDR infections. 

  • Broad-spectrum activity against a wide variety of multi-drug resistant Gram-negative, Gram-positive and anaerobic bacteria. In our recently completed Phase 2 clinical trial of the intravenous formulation of eravacycline, eravacycline demonstrated a high cure rate against a wide variety of multi-drug resistant Gram-negative, Gram-positive and anaerobic bacteria. In addition, in in vitro studies eravacycline demonstrated potent antibacterial activity against Gram-negative bacteria, including E. coli; ESBL-producing Klebsiella pneumoniae; Acinetobacter baumannii; Gram-positive bacteria, including MSRA and vancomycin-resistant enterococcus, or VRE; and anaerobic pathogens. As a result of this broad-spectrum coverage, eravacycline has the potential to be used as a first-line empiric monotherapy for the treatment of cIAI, cUTI, ABSSSI, acute bacterial pneumonias and other serious and life-threatening infections.
  • Favorable safety and tolerability profile. Eravacycline has been evaluated in more than 350 subjects in the Phase 1 and Phase 2 clinical trials that we have conducted. In these trials, eravacycline demonstrated a favorable safety and tolerability profile. In our Phase 2 clinical trial of eravacycline in the treatment of cIAI, no patients suffered any serious adverse events, and safety and tolerability were comparable to ertapenem, the control therapy in the trial. In addition, in the Phase 2 clinical trial, the rate at which gastrointestinal adverse events such as nausea and vomiting that occurred in the eravacycline arms was comparable to the rate of such events in the ertapenem arm of the trial.
  • Convenient dosing regimen. In our completed Phase 2 clinical trial in cIAI, we dosed eravacycline once or twice a day as a monotherapy. If approved as a once- or twice-daily dosed antibiotic, eravacycline could reduce the need for complicated dosing regimens typical of multidrug cocktails and the risk of negative drug-drug interactions inherent to multidrug cocktails.
  • Potential for convenient intravenous-to-oral step-down. In addition to the intravenous formulation of eravacycline, we are also developing an oral formulation of eravacycline. If successful, this oral formulation could enable patients who begin intravenous treatment with eravacycline in the hospital setting to transition to oral dosing of eravacycline either in hospital or upon patient discharge for convenient home-based care. The availability of both intravenous and oral administration and the oral step-down could reduce the length of a patient’s hospital stay and the overall cost of care.

Additionally, in February 2012, Tetraphase announced a contract award from the Biomedical Advanced Research and Development Authority (BARDA) worth up to $67 million for the development of eravacycline, from which Tetraphase may receive up to approximately $40 million in funding. The contract includes pre-clinical efficacy and toxicology studies; clinical studies; manufacturing activities; and associated regulatory activities to position the broad-spectrum antibiotic eravacycline as a potential empiric countermeasure for the treatment of inhalational disease caused by Bacillus anthracis, Francisella tularensis and Yersinia pestis.

 

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