The US Food & Drug Administration (US FDA) has granted Fast Track designations for both the intravenous (IV) and oral formulations of the Tetraphase Pharmaceuticals' lead antibiotic candidate, eravacycline. Tetraphase is investigating the safety and efficacy of eravacycline in its ongoing phase 3 global clinical programme; the IGNITE 1 study is evaluating the IV formulation of eravacycline for the treatment of complicated intra-abdominal infections (cIAI); IGNITE 2 is evaluating eravacycline IV-to-oral step-down therapy for the treatment of complicated urinary tract infections (cUTI).
Fast Track designation is awarded to expedite the study and regulatory review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. Eravacycline became eligible for Fast Track status as a result of being designated a Qualified Infectious Disease Product (QIDP), the QIDP designation also makes eravacycline eligible for priority review and an additional five years of US market exclusivity, if approved. These incentives are part of the Generating Antibiotic Incentives Now Act (GAIN Act), which was enacted in July 2012 as part of the FDA Safety and Innovation Act (FDASIA) and was part of the fifth authorisation of the Prescription Drug User Fee Act (PDUFA V).
"We are delighted that eravacycline has received Fast Track designation for both formulations and for both therapeutic indications being pursued," said Guy Macdonald, president and chief executive officer of Tetraphase. "There is a serious and growing public health threat as a result of the rise in increasingly difficult-to-treat bacterial infections, particularly those caused by multidrug-resistant Gram-negative bacteria. With eravacycline and our pipeline of novel antibiotic candidates, we are attempting to directly address this threat. We look forward to working closely with the FDA as we continue to advance eravacycline through Phase 3 development and through the preparation and submission of our NDA filing, which is targeted for the end of 2015."
IGNITE 1 is a randomised, multi-centre, double-blind, double-dummy, global Phase 3 clinical trial designed to assess the efficacy and safety of eravacycline, dosed intravenously 1.0 mg/kg every 12 hours, compared with ertapenem, dosed intravenously 1 g every 24 hours, in the treatment of cIAI. The trial is designed to enroll 536 adult patients in approximately 100 centres worldwide and to be a non-inferiority (10 per cent margin) study. The primary endpoint is clinical response at the test-of-cure visit in the microbiological intent-to-treat (micro-ITT) patient population.
IGNITE 2 is a two-part, randomised, multi-centre, double-blind, Phase 3 clinical trial designed to assess the efficacy and safety of eravacycline compared with levofloxacin in the treatment of cUTI at approximately 150 clinical trial sites worldwide. The two-part trial features a lead-in portion, in which approximately 120 patients, randomised 1:1:1, will receive eravacycline in one of two IV-to-oral step down dosing cohorts (1.5 mg/kg intravenously every 24 hours followed by 200 mg or 250 mg orally every 12 hours) or levofloxacin (750 mg intravenously every 24 hours followed by 750 mg orally every 24 hours).
Under the planned trial protocol, following treatment of the 120 patients in the lead-in portion of the trial, an evaluation of primary efficacy, safety, and tolerability endpoints will be conducted in a planned interim analysis to determine the dose regimen to be carried forward into the second portion of the trial. An additional 720 patients are expected to then be enrolled and randomised 1:1 to receive the selected dose regimen of eravacycline or levofloxacin. This 720-patient trial is designed to be a non-inferiority (10 per cent margin) study with a primary endpoint of clinical and microbiological response approximately seven days after completion of treatment.
Tetraphase is a clinical-stage biopharmaceutical company using its proprietary chemistry technology to create novel antibiotics for serious and life-threatening multidrug-resistant (MDR) bacterial infections, including many of the MDR Gram-negative bacteria highlighted as urgent public health threats by the Centres for Disease Control and Prevention (CDC). Tetraphase's lead product candidate, eravacycline, is being developed as a broad-spectrum intravenous and oral antibiotic in the IGNITE programme (Investigating Gram-negative Infections Treated with Eravacycline). Two Phase 3 clinical trials are ongoing: IGNITE 1 for the indication of complicated intra-abdominal infections (cIAI) and IGNITE 2 for complicated urinary tract infections (cUTI). Tetraphase has created more than 3,000 novel tetracycline analogs using its technology platform; in addition to eravacycline, Tetraphase has generated multiple preclinical antibiotic candidates that are currently being evaluated for clinical suitability.