SAN DIEGO, April 6, 2017 /PRNewswire/ -- Zavante Therapeutics, Inc., a biopharmaceutical company focused on developing novel therapies to improve the outcomes of hospitalized patients, today announced that the company's investigational product candidate, ZOLYD™ (fosfomycin for injection, also known as ZTI-01), met the primary endpoint of statistical non-inferiority to piperacillin/tazobactam in the pivotal ZEUS™ clinical trial in patients with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP). ZOLYD is a first-in-class injectable epoxide antibiotic with a differentiated mechanism of action and broad spectrum of activity against Gram-negative and Gram-positive pathogens, including multi-drug resistant (MDR) pathogens.
The ZEUS study was a multi-center, randomized, double-blind Phase 2/3 trial designed to evaluate the safety and efficacy of ZOLYD in the treatment of hospitalized adults with cUTI or AP. The primary endpoint of overall success, defined as clinical cure plus microbiologic eradication, was assessed in the microbiologic-modified intent-to-treat population at the test-of-cure visit (Day 19). In the study, ZOLYD met the primary endpoint of statistical non-inferiority compared to piperacillin/tazobactam, with an overall success rate of 64.7% (119/184 patients) versus 54.5% (97/178 patients), respectively, a treatment difference of 10.2% (95% CI: -0.4, 20.8). Clinical cure rates were high and similar between treatment groups (90.8% vs. 91.6%, respectively). Zavante plans to present the complete ZEUS study results at an upcoming infectious disease conference, and expects to submit a new drug application to the U.S. Food and Drug Administration in early 2018.
"In an environment of rapidly increasing resistance, safe and effective antibiotics with activity against MDR pathogens are sorely needed," said Keith Kaye M.D., M.P.H., Professor of Medicine, University of Michigan. "If approved, ZOLYD's unique mechanism of action and broad spectrum of activity would add to the treatment armamentarium when treating seriously ill patients in the hospital."
The ZEUS study enrolled 465 patients who were randomized to receive 6 grams ZOLYD as a one-hour intravenous infusion three times daily (18 grams total daily dose) or 4.5 grams IV piperacillin/tazobactam as a one-hour IV infusion three times daily (13.5 grams total daily dose) for seven days. Oral step-down therapy was prohibited. Patients with concurrent bacteremia received up to 14 days of therapy.
In the ZEUS study safety population, ZOLYD was generally well tolerated. Treatment emergent adverse events (TEAEs) were observed in 42.1% of patients in the ZOLYD arm versus 32.0% of patients in the piperacillin/tazobactam arm. Most TEAEs were mild and transient, and most events did not lead to premature discontinuation of the study drug. Serious adverse events were uncommon, occurring in five patients in the ZOLYD arm and six in the piperacillin/tazobactam arm, and there were no deaths reported during the study.
"Increasing antimicrobial resistance is significantly limiting the number of therapies available to treat infections in U.S. hospitals. We believe that ZOLYD is an important antibiotic with a novel mechanism of action that, if approved, will help fill the void and address the unmet need. The strong trial results advance our goal of making ZOLYD available to U.S. physicians and their patients," said Evelyn J. Ellis-Grosse, Ph.D., Chief Scientific Officer of Zavante Therapeutics. "We are deeply grateful to the investigators and patients who participated in our global cUTI pivotal study and played an important role in potentially advancing a new medicine for life-threatening infections."
"We believe that the results of the ZEUS study bring us one step closer to introducing ZOLYD as a foundational, broad-spectrum antibiotic in the U.S. hospital market," said Ted Schroeder, President and Chief Executive Officer of Zavante. "We recognize the urgent need for new treatment options for patients with complicated urinary tract infections caused by suspected or confirmed multi-drug resistant pathogens. We expect to file our NDA in early 2018 and, if approved, look forward to introducing ZOLYD for appropriate patients who can benefit from a new antibiotic therapy."
About ZOLYD (fosfomycin for injection, also known as ZTI-01)
ZOLYD is a first-in-class injectable epoxide antibiotic with a differentiated mechanism of action that has demonstrated a broad spectrum of bactericidal activity in vitro against both Gram-negative and Gram-positive bacteria, including activity against most contemporary MDR strains. In vitro data have shown that ZOLYD may act synergistically with other antibiotics to improve bacterial killing.
The U.S. Food and Drug Administration (FDA) granted Fast Track designation and Qualified Infectious Disease Product (QIDP) designation for the investigation of ZOLYD for the following indications: cUTI, hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), acute bacterial skin and skin structure infections (ABSSSI), complicated intra-abdominal infections (cIAI). These designations make ZOLYD eligible for certain incentives available for the development of new antibiotics, including priority FDA review and an additional five years of market exclusivity under the Generating Antibiotic Incentives Now (GAIN) Act.
ZOLYD™ is an investigational medication that has not been approved by the FDA for any indication.
About Zavante Therapeutics, Inc.
Zavante Therapeutics, Inc. is a privately-held, late clinical-stage biopharmaceutical company focused on developing novel therapies to improve the outcomes of hospitalized patients. Additional information is available at www.zavante.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of U.S. federal securities laws. Words such as "plans," "expects," and similar expressions are intended to identify forward-looking statements. Forward-looking statements contained in this press release include statements about the anticipated effectiveness of ZOLYD in treating serious infections in hospitalized patients, including those caused by MDR pathogens, and the company's plans and timing for submitting an NDA for, and commercializing, ZOLYD. Forward-looking statements are not historical facts or assurances of the company's future performance, but are based on management's current beliefs, expectations and assumptions and are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and may be outside of the company's control. Because the company's actual results and financial condition may differ materially from those indicated in the forward-looking statements, you should not rely on any such forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in this release include, among others, the following: whether the results of our ZEUS clinical trial are deemed to be sufficient by FDA to support approval of an NDA for ZOLYD; unanticipated delays that may occur, or unanticipated findings that may emerge, in analyzing the data from the ZEUS clinical trial; our ability to successfully complete necessary manufacturing and related development activities for ZOLYD on time and at reasonable costs; our ability to obtain additional financing required to complete development activities and prepare for the commercialization of ZOLYD, if approved by FDA; and potential changes in the FDA's regulatory policies that could negatively impact FDA approval of ZOLYD or the Fast-track or QIDP designations granted by FDA for ZOLYD. Forward-looking statements contained in this press release are based only on information currently available to the company and speak only as of the date made. Zavante undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
ZOLYD, ZEUS and ZAVANTE are trademarks or registered trademarks of Zavante Therapeutics, Inc.
SOURCE Zavante Therapeutics, Inc.