The FDA has granted approval to Iterum Therapeutics' sulopenem etzadroxil and probenecid (Orlynvah) for the treatment of uncomplicated urinary tract infections (uUTIs) in adult women. This approval is specifically for infections caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis when alternative oral antibacterial treatments are limited. The decision marks a significant milestone as it introduces a novel option in uUTI treatment after two decades.
Clinical Trial Data
The approval is supported by data from the Phase 3 SURE 1 (NCT03354598) and REASSURE (NCT05584657) clinical trials. SURE 1 compared sulopenem etzadroxil and probenecid with ciprofloxacin, while REASSURE compared it with amoxicillin and clavulanate (Augmentin). Across both trials, 1932 patients were treated with sulopenem etzadroxil and probenecid.
The SURE 1 trial, a randomized, non-inferiority study, involved 1660 adult women with uUTIs. Results showed that sulopenem etzadroxil and probenecid was effective in patients with ciprofloxacin-resistant pathogens, achieving a composite response rate of 48% compared to 33% in the ciprofloxacin group.
The REASSURE trial, also a randomized, non-inferiority study, included 2214 adult women with uUTIs. In patients infected with amoxicillin/clavulanate-susceptible pathogens, sulopenem etzadroxil and probenecid achieved a composite response rate of 62% compared to 55% in the amoxicillin/clavulanate group.
Expert Commentary
Marjorie Golden, MD, FIDSA, site chief, infectious disease at St. Raphael Campus Yale New Haven Hospital, stated, "The FDA approval of Orlynvah is tremendous new for those of us who have been hoping for a new option to treat appropriate at-risk patients suffering from UTIs. Based on the totality of clinical data generated, Orlynvah has the potential to be an important treatment alternative for use in the community."
Dosage and Limitations
Sulopenem etzadroxil and probenecid is administered as one oral tablet twice daily for 5 days. The FDA specifies that it is not indicated for primary or step-down treatment of complicated UTI or complicated intra-abdominal infections.
Market Context
Up to 60% of women will develop a urinary tract infection during their lifetime, and up to 40% of women with a history of UTI will experience a recurrent infection. Approximately 40 million UTI prescriptions are dispensed annually in the United States, with an estimated 1% caused by antibiotic-resistant bacteria.
Iterum Therapeutics anticipates a commercial launch for Orlynvah in 2025. According to Corey Fishman, CEO of Iterum Therapeutics, "As the first oral penem approved in the US, Orlynvah offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market."
