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Eravacycline (TP-434) is a synthetic fluorocycline antibiotic in development by Tetraphase Pharmaceuticals. It is closely related to the glycylglycine antibiotic tigecycline and the tetracycline class of antibiotics. It has a broad spectrum of activity including many multi-drug resistant strains of bacteria. Phase III studies in complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) were recently completed with mixed results. Eravacylcine has been designated as a Qualified Infectious Disease Product (QIDP), as well as for fast track approval by the FDA.
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Medical Uses
Eravacycline has shown broad spectrum of activity against a variety of Gram-positive and Gram-negative bacteria, including multi-drug resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. It is currently being formulated as for intravenous and oral administration.
Gram-positive organisms
Gram-negative organisms
Similar to other tetracycline derivatives, eravacylcine has is poorly active against Pseudomonas aeruginosa with and MIC90 = 16 mcg/mL (range 0.06-64 mcg/mL). Eravacycline maintains in-vitro activity against Enterobacteriaceae carrying the mcr-1 gene responsible for polymyxin b/colistin resistance.
Complicated Intra-abdominal infections (IGNITE 1)
The IGNITE 1 trial compared twice-daily IV eravacycline to once-daily ertapenem for the treatment of cIAI. A total of 541 patients were included and eravacycline demonstrated noninferiority to ertapenem. An additional pivotal phase 3 study (IGNITE 4) is planned for late 2016 with initial results likely available in the fourth quarter of 2017.
Complicated Urinary Tract infections (IGNITE 2)
The IGNITE 2 trial compared 7 days of IV eravacycline to IV levofloxacin with the option to convert patients in either group to oral therapy after 3 days for cUTI. Overall, eravacyline was inferior to levofloxacin in response rate (60.4 vs 66.9%); however it was noted that patients who completed therapy with the IV formulation had higher response rates, suggesting formulation issues with the oral option. Due to the performance of the IV formulation, an additional phase 3 trial is planned to support a supplemental NDA for the cUTI indication.
Commercial information
Eravacycline is under development by Tetraphase Pharmaceuticals Inc. Tetraphase reported a 3Q loss of $21.1 million. Following the results of the IGNITE 2 study, in which eravacycline demonstrated inferiority to levofloxacin, tetraphase stocks fell by 78%.