The FDA approved oral sulopenem etzadroxil and probenecid (Orlynvah) to treat uncomplicated urinary tract infections (uUTIs) caused by certain bacteria in women with limited or no alternative oral antibacterial treatment options, the agency said Friday.
The drug is a combination of a penem antibacterial (sulopenem etzadroxil) and a renal tubular transport inhibitor (probenecid). It is indicated to treat uUTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis and is the first oral penem approved for use in the U.S., drugmaker Iterum Therapeutics said.
The treatment is not indicated for primary or step-down treatment of complicated UTI or complicated intra-abdominal infections, the FDA emphasized.
The agency’s decision was supported by two phase III noninferiority trials: SURE-1, which compared the safety and efficacy of sulopenem etzadroxil/probenecid versus ciprofloxacin, and REASSURE, which compared it against amoxicillin/clavulanate.
In the SURE-1 study of 1,660 women with uUTI, sulopenem etzadroxil/probenecid showed a composite response rate (combined microbiological and clinical response) of 48% versus 33% in the ciprofloxacin group. In the REASSURE trial of 2,214 women, sulopenem etzadroxil/probenecid showed a composite response rate of 62% compared with 55% in the amoxicillin/clavulanate group.
Clinical trials evaluating the antibiotic in complicated UTI or complicated intra-abdominal infections did not demonstrate effectiveness, the FDA stated.
Sulopenem etzadroxil/probenecid is taken as one tablet twice daily for 5 days. The most common adverse reactions in patients treated with the drug were diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting.
Prescribing information includes warnings for hypersensitivity reactions, Clostridioides difficile-associated diarrhea, and potential exacerbation of gout. The treatment is contraindicated in patients with a history of hypersensitivity reactions to the drug’s components or other beta-lactam antibacterial drugs, people with known blood dyscrasias or uric acid kidney stones, or those taking ketorolac tromethamine.
In 2021, the FDA rejected the oral antibiotic based on mixed data from another phase III trial and recommended that Iterum conduct an additional study. After completing REASSURE, the company resubmitted a new drug application in 2024.
Ahead of an Antimicrobial Drugs Advisory Committee meeting last month, FDA reviewers voiced ongoing concerns about the benefits versus the risks of the oral treatment, including its potential for inappropriate use. FDA advisors echoed those concerns.
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