The FDA has granted approval to Orlynvah (sulopenem etzadroxil and probenecid), a novel oral antibiotic developed by Iterum Therapeutics, for the treatment of uncomplicated urinary tract infections (uUTIs) in adult women who have limited or no alternative oral antibacterial treatment options. This approval marks a significant advancement in addressing the growing challenge of antibiotic resistance in common infections.
Clinical Efficacy and Trial Data
The FDA's decision was primarily based on data from two Phase III non-inferiority trials, SURE-1 and REASSURE. The SURE-1 trial compared sulopenem etzadroxil/probenecid against ciprofloxacin, while the REASSURE trial compared it against amoxicillin/clavulanate. 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.
Mechanism of Action and Indication
Orlynvah combines sulopenem etzadroxil, a penem antibacterial, with probenecid, a renal tubular transport inhibitor. This combination allows for effective treatment of uUTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. It is the first oral penem antibiotic approved for use in the U.S.
Dosage and Administration
The recommended dosage for Orlynvah is one tablet taken orally twice daily for 5 days. Common adverse reactions reported in clinical trials include diarrhea, nausea, vulvovaginal mycotic infection, headache, and vomiting.
Important Safety Information
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.
Addressing Unmet Needs
UTIs are among the most common infections, particularly in women, with approximately 60% of women in the U.S. experiencing at least one uncomplicated UTI during their lifetime. The rise of antibiotic-resistant strains has complicated treatment, making Orlynvah a valuable option for cases where other oral antibiotics are not suitable.
Limitations and Future Considerations
It is important to note that Orlynvah is not indicated for complicated UTIs or complicated intra-abdominal infections. Clinical trials evaluating the antibiotic in these conditions did not demonstrate effectiveness. As with all antibiotics, careful management of Orlynvah use is essential to delay the emergence of bacterial resistance.
