A lot to GAIN: Zavante awaits pivotal data on retro-antibiotic

With the help of the 2012 GAIN Act, Zavante Therapeutics is breathing new life into a decades-old antibiotic.

Antibiotic petri dish agar plate microbiology lab

When the current drugs stop working and there’s a shortage of anything new, what options does the medical community have to combat antibiotic resistance?

Circa 2010, the answer was ‘not a lot.’

It was that dire lack of options that led to a bipartisan initiative dubbed the Generating Antibiotics Incentives Now Act (GAIN Act), signed into effect in 2012. That year, the CDC estimates some 23,000 Americans died from antibiotic-resistant infections.

While the situation remains critical, the GAIN Act is working, said Ted Schroeder, founder and CEO of Zavante Therapeutics.

“The overall intent was to broaden the number of products that were available to U.S. patients,” Schroeder said in a phone interview.

That means new drugs and old drugs that could hold untapped potential.

San Diego, California-based Zavante is chasing the latter. With the passing of the GAIN Act, Cofounder and CSO Evelyn Ellis-Grosse picked up U.S. rights to an old antibiotic known as fosfomycin.

The discovery of fosfomycin dates back to 1969 and it has been used at low doses in regions outside the U.S. for several decades since. It is also sold locally as an oral formulation called Monurol, though Schroeder noted that its bioavailability is low.

In an era of antibiotic resistance, where’s the logic in going back to an older generation of drugs?

Schroeder cites two reasons. The first is the unusually benign safety profile of fosfomycin. It allows Zavante to take a “modernized approach to dosing,” upping the dose and administering it intravenously, he said. It was part of the reason Ellis-Grosse sought out the U.S. rights.

A second distinguishing feature is the drug’s one-of-a-kind “primitive” mechanism of action, which could help extend the life of the drug.

“It doesn’t need a specific binding protein, so the opportunity for cells to evolve around the antibiotic and create a new pathway for resistance is dramatically lower for this antibiotic than it is for the other classes,” he explained.

At a basic level, the drug is also effective against a broad spectrum of Gram-negative and Gram-positive activity, including activity against multi-drug resistant (MDR) pathogens associated with life-threatening infections.

For it to make economic sense, a variety of incentives had to come together for Zavante to launch and raise a $45 million Series A the following year.

Its formulation of fosfomycin, called ZTI-01, was designated a Qualified Infectious Disease Product (QIDP), part of the GAIN Act program. QIDP creates a path for important antimicrobials to receive priority review, fast track designation, and a five-year extension of patent exclusivity.

The latter benefit was critical. Prior to the GAIN Act, the antibiotic would have received just three years of patent exclusivity through the Hatch-Waxman Act of 1984.

“This antibiotic would not even be a discussion if it weren’t for the GAIN Act,” Schroeder said. “With three years of Hatch-Waxman as your only regulatory exclusivity, you couldn’t afford to invest $45 plus million to bring the product to the market here. You just don’t have enough time to make a return on that investment.”

Given a version of this drug is already approved in the United States, ZTI-01 qualifies for a 505(b)(2) regulatory pathway. Existing data and studies can be used as supporting evidence. It allowed Zavante to move directly from Phase 1 through to a pivotal Phase 3 trial in hard-to-treat urinary tract infections. The data readout is expected soon.

All going well, the drug could reach the market by the end of 2018. Once approved, there are many, many possible areas to expand into, Schroeder said.

“This isn’t the answer to the problem, but it’s a significant step forward,” he noted, of the push to get ZTI-01 to the United States to help fight antibiotic resistance here.

Photo: Andrew Brookes, Getty Images