Zavante's plan to take a long-in-the-tooth antibiotic and repurpose it for the U.S. market is gathering pace. The San Diego startup has phase 3 data in hand for its fosfomycin formulation and thinks the numbers are good enough to support an FDA filing early next year.
Zavante's in-licensed fosfomycin, a 45-year-old broad-spectrum antibiotic, has seen wide use in Europe and some other parts of the world as an oral formulation, but never made it to the U.S market. Its patents have long since expired, but thanks to the GAIN Act—which incentivises the development of new antibiotics—Zavante could claim five years or more of marketing exclusivity if it can bag FDA approval.
The new injectable form of the antibiotic, which Zavante has named as Zolyd (ZTI-01), has now been put through its paces in the phase 2/3 ZEUS trial, revealing that it is at least as good as the widely used combination of piperacillin and tazobactam that treats complicated urinary tract infections, including acute pyelonephritis.
The overall treatment success rate with Zavante's drug was 64.7%, higher than the 54.5% response rate with the standard therapy, and clinical cure rates were above 90% in both treatment groups, said the company. Piperacillin/tazobactam is still a widely used and effective therapy, but it is seeing increasing resistance, particularly in some Escherichia coli strains, and that's one reason why the FDA has awarded Zavante fast-track status for Zolyd.
E. coli is the leading cause of UTIs and featured on the World Health organization's recently published list of top bacterial threats.
If the data is sufficiently compelling to convince the FDA to approve, Zavante could head to the U.S. market next year with a first-in-class epoxide antibiotic. The drug—according to the company—offers "a differentiated mechanism of action and broad spectrum of activity against Gram-negative and Gram-positive pathogens, including multi-drug resistant (MDR) pathogens."
The company also hopes to use the FDA's truncated "505(b)(2)" regulatory route for Zolyd, which was designed to allow approval of drugs that aren't new but have meaningful differences to therapies that are currently available. Taking that path will allow Zavante to reference external data in its marketing application, saving valuable time and money.
Zavante raised $45 million last year to fund the development of fosfomycin, CEO Ted Schroeder told Endpoints News on Thursday, and the company will have spent "nearly every nickel" of that fund by the end of the NDA process. The company may choose to self-market the drug or seek a buyer, he added.
"We recognize the urgent need for new treatment options for patients with complicated urinary tract infections caused by suspected or confirmed multidrug resistant pathogens," said Schroeder. "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."