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Zavante Plans FDA Filing After Antibiotic Hits Clinical Trial Goals

Xconomy San Diego — 

As bacteria develop resistance to older antibiotics, doctors are clamoring for new options that work on these drug- resistant strains. Zavante Therapeutics has been researching one drug as a possible alternative and, with results from a key clinical trial now in hand, the company is preparing to file for FDA approval early next year.

San Diego-based Zavante developed its drug fosfomycin (Zolyd) to treat complicated urinary tract infections. But privately held Zavante’s antibiotic is not a new drug. It’s a new version of an old one. Zavante believes an intravenous formulation can achieve better results fighting infections than the oral version of the drug that is now available. Kevin Finney, chief operating officer of Zavante, said via email that IV administration will be a faster and more reliable way of making the drug “bioavailable,” meaning that it will reach high enough concentrations in the bloodstream to have an effect.

“We believe that these optimized blood levels are unachievable through oral dose formulations due to extremely low oral bioavailability,” he wrote.

Fosfomycin was discovered in Spain in 1969, has been marketed in Europe since the 1980s, and is now generic. The drug works by inactivating a protein that bacteria need to form cellular walls and it is used to treat uncomplicated urinary tract infections. In the U.S., fosfomycin is available only as a powder that can be dissolved in liquid and taken orally, according to Merck Manuals. In other parts of the world, such as Europe, the drug is available in both intravenous and oral formulations. Though fosfoymcin is an old antibiotic, it’s still a useful one. Merck Manuals says that the drug’s ability to work on a wide spectrum of bacteria has made the drug a new choice in treating drug-resistant bugs elsewhere in the body.

Zavante has an exclusive licensing agreement with fosfomycin’s primary manufacturer in Europe, Finney said. The Zavante rights to the drug only cover the U.S. But the company has been a pursuing a faster track to the U.S. market via 505(b)(2), an FDA rule covering approvals for new formulations of already approved drugs. That pathway requires only a single clinical trial to show that the new formulation is equivalent to the old one.

Zavante’s Phase 2/3 clinical trial enrolled 465 patients randomized to receive either fosfomycin as a one-hour intravenous infusion administered three times daily, or piperacillin/tazobactam, a combination antibiotic that is also administered as a one-hour IV infusion three times daily. Though that combination drug has worked to treat urinary tract infections, an increase in its use has raised concerns about drug resistance, according to research published in the International Journal of Infectious Diseases.

The main goal of the trial was to show that fosfomycin could cure urinary tract infection comparably to the combination antibiotic. Zavante says that the trial results showed its drug had a 64.7 percent success rate treating these infections. By comparison, the piperacillin/tazobactam combination had a 54.5 percent success rate. Zavante says it will present complete results from the clinical trial at an upcoming infectious disease conference.

The fosfomycin clinical trial results mean that there now might be two new antibiotics heading to the FDA early next year to help address the problem of drug-resistant bacteria. Earlier this week, Paratek Pharmaceuticals (NASDAQ: PRTK) reported clinical trial results showing that its antibiotic, omadacycline, hit the goals of a clinical trial that tested the drug in 774 patients with hospital-acquired pneumonia. With the new data, Boston-based Paratek plans to file for U.S. approval in the first quarter of 2018.

Besides a faster regulatory pathway, the Zavante drug was also granted “fast track” designation from the FDA in 2015, which provides for a speedier review of the drug application. That designation applies to other potential uses of the drug, including abdominal infections, pneumonia, and skin infections. The Zavante drug is in early stage clinical trials for those infections.

If Zavante wins FDA approval on its intravenous form of fosfomycin in urinary tract infections, it will have an additional five years to exclusively market its drug without facing generic competition, according to provisions of the Generating Antibiotics Incentives Now law. The 2012 statute extended marketing exclusivity as a way encouraging drug companies to develop new drugs that treat serious or life-threatening infections.

Zavante’s clinical trial results come a little more year after the company raised $45 million in a Series A round of funding to support the fosfomycin clinical trial. Frazier Healthcare Partners and Longitude Capital led the round, which also included participation from Aisling Capital.

Image of E. coli bacteria by Flickr user NIAID via a Creative Commons license.