Tetraphase Pharmaceuticals, Inc., a clinical-stage life science company developing novel antibiotics effective against antibiotic-resistant bacteria, presented new, positive Phase 2 clinical data on its lead drug candidate, eravacycline (TP-434), on September 11, 2012, at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco, CA. The results of the study show that eravacycline was highly active against drug-resistant bacterial pathogens, demonstrating infection cure rates similar to that of ertapenem (the comparator drug used in the trial) for the treatment of cIAI and a strong safety profile (with low rates of gastrointestinal side effects). These data support Phase 3 development of eravacycline for the treatment of serious infections, including those caused by resistant gram-negative pathogens.
"The rapid rise of multi-drug-resistant bacterial infections (MDR) is a major global public health concern, especially with regard to MDR gram-negative infections where currently approved products are increasingly ineffective and few new therapeutic agents are in clinical development," said Guy Macdonald, President and Chief Executive Officer of Tetraphase Pharmaceuticals. "The outstanding clinical and safety results of Tetraphase's Phase 2 study of eravacycline support this antibiotic's potential for the treatment of patients with some of the most drug-resistant bacterial infections. Eravacycline has the opportunity to meet this urgent medical need both as an I.V. formulation and potentially as an oral stepdown therapy for use when a patient is discharged from the hospital."
In this randomized, double-blind, double-dummy Phase 2 trial of eravacycline, patients with documented cIAI were randomized (2:2:1) into one of three arms to receive eravacycline at 1.5 mg/kg IV QD intravenously, eravacycline at 1.0 mg/kg BID intravenously, or ertapenem at 1 g intravenously QD. Investigators obtained baseline intra-abdominal cultures at the time of operation and treated patients for up to 14 days. Ten to 14 days after end of therapy, patients returned for a test of cure (TOC) visit. Clinical outcomes, microbiological outcomes and safety parameters were recorded at all visits. The primary efficacy endpoint was clinical outcome at TOC visit in the microbiologically evaluable population.
The trial enrolled 143 patients [75 (or 52.4 percent) with complicated appendicitis and 68 (or 47.6 percent) with other diagnoses]. Treatment arms were well matched for baseline characteristics. A total of 191 pathogens were isolated from 109 patients in the ME population. Isolates included Escherichia coli (n = 86), Klebsiella spp. (n = 20), Acinetobacter spp. (n = 5) Pseudomonas aeruginosa (n = 6), enterococci (n = 13), streptococci (n = 18), Staphylococcus aureus (n = 6) and Bacteroides spp. (n = 11). All treatment arms in the trial demonstrated cure rates in the ME population of between 93 and 100 percent. There were no serious adverse events related to eravacycline. Overall adverse events, including low rates of gastrointestinal side effects, were not significantly different among the randomized groups.
"The Phase 2 trial exceeded expectations and demonstrates that eravacycline has the potential to become an important option for treating serious intra-abdominal infections and other serious infectious health threats, where today there is only one class of drug left that is not yet resistant," said Joseph S. Solomkin, M.D., Professor emeritus, Department of Surgery, University of Cincinnati College of Medicine and lead author on the poster presented at ICAAC. "Late-stage development of this type of antibiotic is exactly what infectious disease physicians and the U.S. government are advocating for, particularly given its potential to be used empirically (when physicians are unclear which bacteria may be causing the infection)."
Eravacycline is a potent new antibiotic effective against MDR gram-negative pathogens. Eravacycline is also effective against the broadest spectrum of other difficult-to-treat and MDR pathogens, including MDR gram-positive, anaerobic, and atypical species. Eravacycline's spectrum and pharmacokinetic properties are consistent with its use as a once-daily monotherapy.
Source: Tetraphase Pharmaceuticals Inc.