Maryland: Five months after signing off on Utility Therapeutics’ Pivya as the first new treatment for uncomplicated urinary tract infections (uUTIs) in more than two decades, the FDA is weighing the pros and cons of another oral treatment in the indication.
Iterum’s sulopenem (sulopenem etzadroxil/probenecid), which was initially rejected by the US regulator in 2021, is back for another swing, with a target decision date set for October 25.
On Monday, an FDA advisory committee will put sulopenem under its microscope, fleshing out concerns that “inappropriate use” of the treatment could cause antimicrobial resistance (AMR), according to an FDA briefing document (PDF).
There also is concern that inappropriate use of sulopenem could increase “cross-resistance to other carbapenems,” the FDA added, referring to the class of drugs that treat severe bacterial infections, often as a last-resort measure.
On the plus side, an approval for sulopenem would “potentially address an unmet need,” the FDA wrote, as it would become the first oral therapy from the penem class to reach the market as a treatment for uUTIs. Additionally, it could be provided in an outpatient visit, as opposed to the administration of intravenous therapies which can require hospitalization.
Three years ago, the FDA turned down Iterum’s application for sulopenem, asking for a new trial. Iterum’s prior phase 3 study showed the drug beat another antibiotic, ciprofloxacin, at treating infections in patients whose infections resisted that antibiotic. But it was inferior to ciprofloxacin in treating those whose pathogens were susceptible to the older antibiotic.
In January of this year, Dublin-based Iterum revealed that the phase 3 REASSURE study showed that sulopenem was non-inferior to Augmentin (amoxicillin/clavulanate), producing a 62% response rate versus 55% for the comparator.
The FDA, however, in its briefing documents pointed out that neither of Iterum’s phase 3 trials were “designed to evaluate the efficacy of the study drug for the treatment of uUTI caused by resistant bacterial isolates.”
The FDA also noted that the trials weren’t designed to evaluate Iterum’s prospect in uUTI patients who had failed first-line treatment.
Over the years, antibiotic treatments have become less effective as resistance to them has increased. More than 1 in 5 who receive treatment are now resistant, which can lead to progression of infections, including life-threatening sepsis.
The void is significant as more than 30 million uUTIs are diagnosed every year in the U.S., with nearly half of all women contracting the infection at some point in their life. Outside of a hospital setting, UTIs account for more antibiotic use than any other disorder.
