Watertown, MA — Tetraphase Pharmaceuticals, Inc. (NASDAQ:TTPH), a clinical stage biopharmaceutical company developing novel antibiotics to treat life-threatening multidrug-resistant (MDR) infections, today announced positive top-line results from IGNITE 1, the Company’s Phase 3 clinical trial of eravacycline for the treatment of complicated intra-abdominal infection (cIAI) compared to ertapenem. In the trial, eravacycline met the primary endpoint of statistical non-inferiority of clinical response at the test-of-cure (TOC) visit, under the guidance set by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
The primary analysis under the FDA guidance was conducted using a 10% non-inferiority margin in the microbiological intent-to-treat (micro-ITT) population. In the micro-ITT population, the lower and upper bounds of the 95% confidence interval were -7.1% and 5.5%, respectively. Under the EMA guidance, the primary analysis was conducted using a 12.5% non-inferiority margin of the clinically evaluable (CE) patient population. In the CE population, the lower and upper bounds of the 95% confidence interval were -6.3% and 2.8%, respectively. The secondary analyses were consistent with and supportive of the primary outcome.
There were no drug-related serious adverse events in the trial. The most commonly reported drug-related adverse events for eravacycline were gastrointestinal, including nausea (3.3%) and emesis (2.2%). This adverse event profile for eravacycline was consistent with that seen in the Phase 2 clinical trial of eravacycline in cIAI.
The spectrum of pathogens in this trial was similar to that seen in other pivotal trials in this patient population. The most common Gram-negative pathogens in the study included Escherichia coli, Klebsiella pneumonia, Pseudomonas and Bacteroides.
“The prevalence of potentially deadly, multi-drug-resistant bacterial infections has grown rapidly in recent years and is currently a major global public health concern, especially in resistant Gram-negative infections where many current antibiotic treatment options are increasingly ineffective,” commented Joseph Solomkin, M.D., Professor Emeritus in the Department of Surgery at the University of Cincinnati College of Medicine and advisor to the Company. “These IGNITE 1 trial results suggest that eravacycline has the potential to be a new treatment option for serious intra-abdominal infections, and possibly other serious bacterial infections, where new treatments are urgently needed for patients.”
“The positive results from IGNITE 1 underscore that treatment with eravacycline could help a significant number of cIAI patients achieve a clinical cure for their difficult-to-treat Gram-negative infections,” said Guy Macdonald, President and CEO of Tetraphase. “The success of this trial is an important milestone for the eravacycline pivotal program. These results, along with those from our ongoing Phase 3 IGNITE 2 trial in complicated urinary tract infections (cUTI) which are expected in mid-2015, would form the basis of regulatory submissions seeking approval for eravacycline in both indications. We continue to target a New Drug Application submission to the FDA by the end of 2015.”
Tetraphase plans to submit the data from the Phase 3 IGNITE 1 clinical trial for presentation at a scientific meeting in 2015.
About IGNITE 1
IGNITE 1 is a randomized, multi-center, 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. Per the trial design, 541 adult patients were enrolled in the trial in 66 centers worldwide. Under the guidance set by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the primary endpoint of the trial is clinical response at the test-of-cure (TOC) visit in the two treatment arms. For the FDA, the primary analysis is conducted using a 10% non-inferiority margin in the microbiological intent-to-treat (micro-ITT) population. For the EMA, the primary analysis is conducted using a 12.5% non-inferiority margin of the clinically evaluable patient population. Secondary endpoints include the microbiologic response in the treatment arms at the end of treatment, TOC and follow-up visits in the micro-ITT and microbiologically evaluable populations. The TOC visit takes place 25 to 31 days after the initial dose of eravacycline. The follow-up visit takes place 38 to 50 days after the initial dose of eravacycline.
About IGNITE 2
IGNITE 2 is a two-part, randomized, multi-center, 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 recently completed lead-in portion which was designed to determine the dose regimen to be carried forward into the pivotal portion of the trial. For the pivotal portion, 720 patients are expected to be enrolled and randomized 1:1 to receive eravacycline or levofloxacin (1.5 mg/kg intravenously every 24 hours followed by 200 mg orally every 12 hours) or levofloxacin (750 mg intravenously every 24 hours followed by 750 mg orally every 24 hours). This pivotal portion of the trial is designed to be a non-inferiority (10% margin) study. The primary endpoint for the FDA is the responder outcome (a combination of clinical cure rate and microbiological response) in the Microbiological Intent-to-Treat (micro-ITT) Population at the Post-Treatment visit (defined as 6-8 days after the completion of therapy). For the EMA, the primary endpoint is the microbiological response in the micro-MITT and microbiologically evaluable populations at the Post Treatment visit. Top-line results from the pivotal portion of the study are expected to be available in mid-2015.
Tetraphase’s lead product candidate, eravacycline, is being developed as a broad-spectrum intravenous and oral antibiotic in the IGNITE program (Investigating Gram-negative Infections Treated with Eravacycline). Under this program, 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). Eravacycline has been designated by the U.S. Food and Drug Administration as a Qualified Infectious Disease Product (QIDP) for both the cIAI and cUTI indications. This designation, which is assigned to qualifying new antibiotic product candidates, makes eravacycline eligible to benefit from certain development and commercialization incentives, including priority review, and eligibility for both fast-track status and an additional five years of U.S. market exclusivity.
About Tetraphase Pharmaceuticals, Inc.
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 those caused by many of the MDR Gram-negative bacteria highlighted as urgent public health threats by the Centers for Disease Control and Prevention (CDC). Tetraphase has created more than 3,000 novel tetracycline analogs using its proprietary technology platform. Please visit www.tphase.com for more company information.
Any statements in this press release about our future expectations, plans and prospects, including statements regarding our strategy, future operations, prospects, plans and objectives, and other statements containing the words “anticipates,” “believes,” “expects,” “plans,” “will” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether our cash resources will be sufficient to fund our continuing operations for the period we anticipate; whether the top line results from the lead in portion of IGNITE 2 will be predictive of the final results of the trial; whether eravacycline will advance through the clinical trial process on a timely basis or at all; whether enrollment for clinical trials will be achieved in the time frame expected; whether submissions will be made and approvals will be received from the United States Food and Drug Administration or equivalent foreign regulatory agencies on a timely basis or at all; whether, if eravacycline obtains approval, it will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of our most recent Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission on November 10, 2014. In addition, the forward-looking statements included in this press release represent our views as of December 17, 2014. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so.