FDA Approves New Antibiotic for Uncomplicated UTIs

The US Food and Drug Administration (FDA) approved a new oral one antibiotic for the treatment of uncomplicated urinary tract infections (uUTIs).

Orlynvah (sulopenem etzadroxil and probenecid) is a broad-spectrum oral penem antibiotic designed for the treatment of urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis bacteria in adult women who have limited or no alternative treatment options. Iterum Therapeutics created the drug.

The FDA said it approved the drug in part based on two randomized, controlled Phase 3 trials that compared Orlynvah with standard treatments for uUTIs.

In a study of 2,214 adult women with uUTI, women receiving Orlynvah had a composite response rate of 62% (combined microbiological and clinical response), compared to a composite response rate of 55% in patients treated with amoxicillin/clavulanate. In another study of 1,660 adult women with urinary tract infections caused by ciprofloxacin-resistant pathogens, Orlynvah was superior to ciprofloxacin, with a composite response rate of 48% compared to 33% in the ciprofloxacin group.

The most common side effects women experienced when using Orlynvah were diarrhea, nausea, vaginal yeast infection, headache and vomiting.

“Orlynvah offers new hope for patients suffering from difficult-to-treat urinary tract infections,” said Corey Fishman, interim CEO of Iterum Therapeutics, in a statement press release. “As the first oral penem approved in the U.S., Orlynvah provides an excellent alternative treatment option for appropriate patients in the underserved uUTI market.”

At the FDA’s Antimicrobial Drug Advisory Committee meeting on September 10, committee members agreed that Orlynvah could be beneficial for some patients, but were concerned that off-label use could increase resistance to carbapenems, which are closely related to penems and an important class of antibiotics. for serious, multidrug-resistant infections.

“Although an oral penem for the treatment of resistant bacteria causing uUTI may address an unmet need, its use in an outpatient setting where treatment is usually empirical raises concerns about inappropriate use that may contribute to AMR (antimicrobial resistance),” The agency writes this in a document.

Careful antimicrobial stewardship is “necessary to ensure appropriate positioning of sulopenem etzadroxil/probenecid in the hierarchy of treatment options for uUTI.” Orlynvah is the first oral penem approved in the US. The FDA’s prescribing information states that Orlynvah should only be used to treat urinary tract infections that are (suspected) caused by sensitive bacteria. The drug is not approved as a primary or follow-up treatment for complicated urinary tract infections or for complicated intra-abdominal infections.