The FDA has granted approval to Orlynvah (sulopenem etzadroxil and probenecid), a novel oral antibiotic, for the treatment of uncomplicated urinary tract infections (uUTIs) in women who have limited or no alternative oral antibacterial treatment options. This decision comes despite some initial concerns raised by FDA reviewers regarding the risk-benefit profile and potential for inappropriate use.
Orlynvah, developed by Iterum Therapeutics, is a combination of a penem antibacterial (sulopenem etzadroxil) and a renal tubular transport inhibitor (probenecid). It is specifically indicated for uUTIs caused by susceptible isolates of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. This marks the first oral penem antibiotic approved for use in the United States.
The FDA's approval was primarily supported by data from two Phase 3 non-inferiority trials: SURE-1 and REASSURE. The SURE-1 trial compared sulopenem etzadroxil/probenecid to ciprofloxacin, while the REASSURE trial compared it to amoxicillin/clavulanate.
Clinical Trial Results
In the SURE-1 study, involving 1,660 women with uUTIs, sulopenem etzadroxil/probenecid demonstrated a composite response rate (combined microbiological and clinical response) of 48% compared to 33% in the ciprofloxacin group. The REASSURE trial, which included 2,214 women, showed a composite response rate of 62% for sulopenem etzadroxil/probenecid versus 55% for amoxicillin/clavulanate.
The recommended dosage for Orlynvah is one tablet taken twice daily for five days. Common adverse reactions observed in clinical trials included diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting. The prescribing information includes warnings for hypersensitivity reactions, Clostridioides difficile-associated diarrhea, and potential exacerbation of gout.
Important Considerations
Orlynvah is contraindicated in patients with a history of hypersensitivity reactions to penems or beta-lactam antibacterial drugs, those with known blood dyscrasias or uric acid kidney stones, and those taking ketorolac tromethamine. It is important to note that clinical trials evaluating the antibiotic in complicated UTIs or complicated intra-abdominal infections did not demonstrate effectiveness, and the drug is not indicated for these conditions.
The FDA had previously rejected the oral antibiotic in 2021 based on mixed data from an earlier Phase 3 trial, recommending that Iterum conduct an additional study. Following the completion of the REASSURE trial, the company resubmitted a new drug application in 2024, leading to the current approval.
