From speedy review to standstill: FDA spurns Iterum's antibiotic, demands another trial

Exactly six months after granting Iterum’s oral antibiotic a speedy review, the FDA rejected the application saying more data are needed from at least one additional trial.

Iterum received a complete response letter from the agency on Friday declining to approve the drug, the company revealed on Monday. Iterum is seeking approval for the drug, sulopenem etzadroxil/probenecid, for the treatment of uncomplicated urinary tract infections (UTI) in patients for whom the quinolone class of antibiotics does not work. 

The drug’s application is based on a phase 3 study pitting it against ciprofloxacin, a drug in the fluoroquinolone class of antibiotics. In the letter, the FDA said the trial showed that sulopenem beat ciprofloxacin at treating infections in patients whose infections were resistant to ciprofloxacin. But it wants more data to support an approval in Iterum’s intended indication. 

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The company should carry out at least one more trial “potentially using a different comparator drug,” the FDA recommended, according to a statement. And some nonclinical work could also be done to figure out the best dosing regimen for sulopenem, though the FDA said this recommendation would not affect the drug’s approvability. 

The company has enough cash for the next couple of years, according to the statement, but the delay in sulopenem's timeline could spook investors.

“Though the company is at a comfortable cash position of ~$100M that enables a runway into 2023, we believe the regulatory setback could delay the timeline by at least two years with additional trialing and could pose challenges ahead to salvage investor interest around the asset,” wrote RBC Capital Markets analyst Gregory Renza in a note to clients on Monday.

Iterum will review the letter with advisers and request a meeting with the FDA, according to the statement. That meeting is expected to take place in the third quarter. 

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Sulopenem started 2021 with a bright outlook, nabbing a speedy review from the FDA, which planned to decide the drug’s fate by July 25. The FDA’s eventual decision wasn’t a surprise given the agency warned Iterum in early July of “deficiencies” in the application. The news came in a letter that did not detail what the deficiencies were, the company said at the time.

Iterum’s stock plunged more than 35% to $1.47 apiece at the time and has been generally trending downward ever since, closing at $1.13 on Friday. Shares plummeted 36% to 72 cents as the markets opened Monday. 

Besides uncomplicated urinary tract infections, Iterum developing sulopenem as an intravenous and oral treatment for complicated UTI, as well as for complicated intraabdominal infections. The drug is a Pfizer castoff, shelved in 2010 and offloaded to Iterum in 2015 in exchange for an upfront payment, a stake in Iterum and the chance to receive more equity, milestone payments and royalties later on.

The rejection is a blow to a field that, despite the rise of drug-resistant bugs and a need for new medicines, has lagged behind other areas, such as cancer and rare disease. In 2020, the FDA approved Shionogi’s Fetroja and Merck’s Recarbrio in new indications, but there have been very few new antibiotics approved in the last 30 years. 

Big companies have retreated from antimicrobials research, while many small biotechs trying to pick up the slack have stumbled. Within a year, antibiotics makers Aradigm, Achaogen and Melinta all filed for bankruptcy protection. Investment firm Deerfield Management gave Melinta a lifeline out of bankruptcy in March 2020 and three months later, the antibiotics maker struck a deal to acquire Tetraphase and its approved drug Xerava. But it eventually lost out to a "superior offer" from La Jolla Pharmaceutical.

Big Pharma companies such as Johnson & Johnson, Merck and Pfizer banded together in 2020 to pool $1 billion into a new fund that aims to see two to four new antibiotics through approval by 2030. The fund, dubbed the AMR Action Fund, recently added another $140 million to its coffers. 

Editor's note: This story has been updated to correct details about Melinta and Tetraphase.