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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.
- 1 Medical Uses
- 2 Clinical Trials
- 3 Commercial information
- 4 References
- 5 External links
- 6 Notes
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.
- Staphylococcus aureus (both methicillin-resistant and sensitive strains)
- Streptococcus pneumonia
- Enterococcus faecalis
- Enterococcus faecium (including vancomycin resistant strains)
- Non-lactose fermenting Gram-negative bacteria
- Haemophilus influenzae
- Moraxella catarrhalis
- Nesseria gonorrhoeae
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.
Phase 3 trials
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.
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.
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%.
- Solomkin, Joseph; Evans, David; Slepavicius, Algirdas; Lee, Patrick; Marsh, Andrew; Tsai, Larry; Sutcliffe, Joyce A.; Horn, Patrick (2016-11-16). "Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial". JAMA surgery. doi:10.1001/jamasurg.2016.4237. ISSN 2168-6262. PMID 27851857.
- "Tetraphase Announces Top-Line Results From IGNITE2 Phase 3 Clinical Trial of Eravacycline in cUTI (NASDAQ:TTPH)". ir.tphase.com. Retrieved 2016-11-20.
- "FDA Grants QIDP Designation to Eravacycline, Tetraphase's Lead Antibiotic Product Candidate | Business Wire". www.businesswire.com. Retrieved 2016-11-20.
- Zhanel, George G.; Cheung, Doris; Adam, Heather; Zelenitsky, Sheryl; Golden, Alyssa; Schweizer, Frank; Gorityala, Bala; Lagacé-Wiens, Philippe R. S.; Walkty, Andrew (2016-04-01). "Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent". Drugs. 76 (5): 567–588. doi:10.1007/s40265-016-0545-8. ISSN 1179-1950. PMID 26863149.
- Sutcliffe, J. A.; O'Brien, W.; Fyfe, C.; Grossman, T. H. (2013-11-01). "Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens". Antimicrobial Agents and Chemotherapy. 57 (11): 5548–5558. doi:10.1128/AAC.01288-13. ISSN 1098-6596. PMC . PMID 23979750.
- Solomkin, Joseph S.; Ramesh, Mayakonda Krishnamurthy; Cesnauskas, Gintaras; Novikovs, Nikolajs; Stefanova, Penka; Sutcliffe, Joyce A.; Walpole, Susannah M.; Horn, Patrick T. (2014-01-01). "Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections". Antimicrobial Agents and Chemotherapy. 58 (4): 1847–1854. doi:10.1128/AAC.01614-13. ISSN 1098-6596. PMC . PMID 24342651.
- Abdallah, Marie; Olafisoye, Olawole; Cortes, Christopher; Urban, Carl; Landman, David; Quale, John (2015-03-01). "Activity of eravacycline against Enterobacteriaceae and Acinetobacter baumannii, including multidrug-resistant isolates, from New York City". Antimicrobial Agents and Chemotherapy. 59 (3): 1802–1805. doi:10.1128/AAC.04809-14. ISSN 1098-6596. PMC . PMID 25534744.
- Fyfe, Corey; LeBlanc, Gabrielle; Close, Brianna; Nordmann, Patrice; Dumas, Jacques; Grossman, Trudy H. (2016-08-22). "Eravacycline is active against bacterial isolates expressing the polymyxin resistance gene mcr-1". Antimicrobial Agents and Chemotherapy. 60: 6989–6990. doi:10.1128/AAC.01646-16. ISSN 0066-4804. PMC . PMID 27550359.
- "http://www.healio.com/infectious-disease/antimicrobials/news/online/%7B3b5e5b8a-a5eb-4739-a402-3c88c22621d4%7D/phase-3-ignite4-trial-to-examine-safety-efficacy-of-iv-eravacycline-in-ciais". www.healio.com. Retrieved 2016-11-20. External link in
- "Tetraphase Pharmaceuticals Provides Update on Eravacycline Regulatory and Development Status (NASDAQ:TTPH)". ir.tphase.com. Retrieved 2016-11-20.
- "http://www.healio.com/infectious-disease/antimicrobials/news/online/%7B8b0a64f5-6a4c-4b88-b5ac-9c1fe100778c%7D/ignite2-eravacycline-inferior-to-levofloxacin-but-iv-formulation-shows-promise". www.healio.com. Retrieved 2016-11-20. External link in
- "Tetraphase reports 3Q loss". Retrieved 2016-11-20.
- Feroldi, Brian (2016-11-20). "Why Tetraphase Pharmaceuticals Dropped 74% of Its Value in 2015 -- The Motley Fool". The Motley Fool. Retrieved 2016-11-20.
- "Tetraphase Announces Top-Line Results From IGNITE2 Phase 3 Clinical Trial of Eravacycline in cUTI: Eravacycline Did Not Achieve Primary Endpoint in Pivotal Portion of cUTI Trial"
- Tetraphase pipeline