WATERTOWN, Mass., April 27, 2015 (GLOBE NEWSWIRE) -- Tetraphase Pharmaceuticals, Inc. (Nasdaq:TTPH), a clinical stage biopharmaceutical company developing novel antibiotics to treat life-threatening multidrug-resistant (MDR) infections, today announced the first detailed results from phase 3 clinical trials of its lead drug candidate, eravacycline, in development to treat complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). These results are being presented at the 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), taking place on April 25-28 in Copenhagen, Denmark.
"The detailed clinical data presented this year at ECCMID continues to support eravacycline's potential as a potent antibiotic option to treat both cIAI and cUTI infections," said Guy Macdonald, President and CEO of Tetraphase. "We believe that eravacycline will offer physicians additional options when treating bacterial infections given its activity against a wide variety of bacterial pathogens, including multidrug-resistant Gram-negative bacteria, and, in cUTI, its potential as an IV-to-oral transition therapy. We are encouraged by the results achieved in both IGNITE1 (cIAI) and the lead-in portion of IGNITE2 (cUTI) and we look forward to reporting top-line results from the pivotal portion of IGNITE2 in mid-2015."
Mr. Macdonald continued: "Beyond the phase 3 eravacycline program, preclinical data were also presented at ECCMID from our earlier-stage antibiotic programs. For TP-271, IND-enabling data were presented demonstrating significant in vivo activity against methicillin-resistant staphylococcus aureus (MRSA) and Streptococcus pneumoniae in a preclinical lung infection model. For TP-6076, the lead candidate from our second-generation discovery program, we reported promising preclinical data supporting its potential as a treatment for serious MDR gram-negative infections."
IGNITE1 – Phase 3 Clinical Trial in cIAI
In IGNITE1, eravacycline met the primary endpoint of statistical non-inferiority of clinical response at the test-of-cure (TOC) visit. The primary analysis under the U.S. Food and Drug Administration (FDA) guidance was conducted using a 10% non-inferiority margin in the microbiological intent-to-treat (micro-ITT) population (n=446). Under the European Medicines Agency (EMA) guidance, the primary analysis was conducted using a 12.5% non-inferiority margin of the clinically evaluable (CE) patient population (n=477).
In the micro-ITT population, 86.8% of patients receiving eravacycline achieved a clinical cure compared to 87.6% of patients receiving ertapenem. The lower and upper bounds of the 95% confidence interval were -7.1% and 5.5%, respectively. In the CE population, 92.9% of patients receiving eravacycline achieved a clinical cure compared to 94.5% of patients receiving ertapenem. The lower and upper bounds of the 99% confidence interval were -7.9% and 4.4%, respectively.
The most common Gram-negative pathogens in the study included Escherichia coli, Klebsiella pneumonia and Pseudomonas. Eravacycline achieved high cure rates against these pathogens, as well as in patients with Acinetobacter baumannii and in patients with suspected ESBL-producing pathogen isolates.
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%, n=9) and emesis (2.2%, n=6).
"Eravacycline is a novel antibiotic drug candidate that is being developed for the treatment of common, but serious infections, including complicated intra-abdominal infections that may either be community-acquired or following surgical procedures," said Joseph Solomkin, M.D., Professor Emeritus in the Department of Surgery at the University of Cincinnati College of Medicine and advisor to Tetraphase. "The data being presented at ECCMID this year show that eravacycline has the potential to be a new treatment option for complicated intra-abdominal infections, and possibly other serious bacterial infections, where new treatments remain urgently needed for infections with multidrug-resistant bacteria."
Lead-in Portion of IGNITE2 – Phase 3 Clinical Trial in cUTI
In the lead-in portion of IGNITE2, both IV-to-oral dosing regimens of eravacycline (1.5 mg/kg IV followed by 200 mg or 250 mg) compared favorably to levofloxacin for the treatment of cUTI, supporting the advancement of the trial into its pivotal portion. Efficacy outcomes were microbiological success and responder rates (defined as subjects with both clinical cure and successful microbiological outcome) in all randomized subjects (n=143) with a baseline pathogen identified (micro-ITT population, n=75) and the microbiologically evaluable (ME) population (n=62) at a post-treatment visit 7 days after the last dose of study drug. Patient demographics were well matched across all treatment groups.
In the micro-ITT population, the responder outcome, which was the primary endpoint for the FDA, for the IV-to-oral 200 mg (n=24), IV-to-oral 250 mg (n=28) and levofloxacin groups (n=23) were 70.8%, 64.3% and 52.2%, respectively. Microbiological response was 75.0%, 64.3% and 56.5%, respectively. In the ME population, the microbiological response, which was a primary endpoint for the EMA, were 83.3% (n=18), 78.2% (n=23) and 61.9% (n=21), respectively. The pharmacokinetics for both oral doses of eravacycline were comparable to the IV formulation.
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 pneumoniae, and Enterococci. Responder rates for levofloxacin resistant isolates (n=24) were 83.3% for eravacycline IV-to-oral 200 mg, 72.7% for eravacycline IV-to-oral 250 mg and 42.9% for levofloxacin.
There were no drug-related serious adverse events. The most common drug-related treatment emergent adverse events in all arms were gastrointestinal and were mild to moderate. In the eravacycline IV-to-oral 200 mg group the gastrointestinal disorders included nausea (6.4%; n=3), emesis (4.3%; n=2), and nausea and emesis (6.4%; n=3) with only one of these events leading to discontinuation of study drug.
Based on these data, Tetraphase selected the 200 mg eravacycline oral dose for the pivotal portion of the phase 3 study that is currently underway.
For more information regarding presentations of eravacycline phase 3 data in cIAI and cUTI, as well as other Tetraphase presentations at ECCMID, visit the ECCMID website at http://www.eccmid.org/.
About IGNITE1
IGNITE1 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 FDA and the 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 IGNITE2
IGNITE2 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.
About Eravacycline
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). This program includes two phase 3 clinical trials: IGNITE1 for the indication of complicated intra-abdominal infections (cIAI) and IGNITE2 for complicated urinary tract infections (cUTI). Eravacycline has been designated by the FDA 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 MDR bacterial infections, including those caused by many of the MDR Gram-negative bacteria highlighted as urgent public health threats by the CDC. Tetraphase has created more than 3,000 novel tetracycline analogs using its proprietary technology platform. Tetraphase's pipeline includes eravacycline, a broad-spectrum intravenous and oral antibiotic that is being evaluated in phase 3 clinical trials, and two preclinical antibiotic candidates, TP-271 and TP-6076. Please visit www.tphase.com for more company information.
Forward-Looking Statements
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 results obtained in preclinical studies and early or interim clinical trials will be indicative of results obtained in future clinical trials; whether eravacycline will advance through the clinical trial process on a timely basis; whether the results of the Company's trials will warrant regulatory submission and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether, if eravacycline obtains approval, it will be successfully distributed and marketed; and other factors discussed in the "Risk Factors" section of our annual report on Form 10-K, filed with the Securities and Exchange Commission on March 6, 2015. In addition, the forward-looking statements included in this press release represent our views as of April 27, 2015. 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.