FDA approves new oral antibiotics for urinary tract infections

US Food and Drug Administration (FDA) last week accepted a new oral antibiotic for the treatment of uncomplicated urinary tract infections (UUTIs).

The antibiotic, Orlynvah (sulopenem etzadroxil and probenecid), is a broad-spectrum oral penem antibiotic indicated for treating UUTI caused by certain bacteria.Escherichia coli, Klebsiella pneumoniae, or Proteus is very good) in older women with little or no other treatment options. This drug is manufactured by Iterum Therapeutics.

The FDA said the approval was based on part of a randomized controlled phase 3 trial in which Orlynvah was compared to standard treatment options for UUTIs. In a trial involving 2,241 older women who had a UTI (the REASSURE trial), patients with amoxicillin/clavulanate infections who received Orlynvah had a pooled response rate of 62% ( combined microbiologic and clinical response), compared with a combined response rate of 55%. in patients treated with amoxicillin/clavulanate – a finding showing non-inferiority.

In another trial (SURE-1), conducted in 1,660 older women with UTI caused by bacteria resistant to ciprofloxacin, Orlynvah was found to be superior to ciprofloxacin, with a pooled response rate of 48% when compared to 33% in the ciprofloxacin group.

The most common side effects of Orlynvah in trial participants were diarrhea, nausea, vaginal yeast infection, headache and vomiting.

Company officials welcomed the news.

“Orlynvah offers new hope for patients with difficult-to-treat UTIs,” Iterum CEO Corey Fishman said in a statement to the company. Press release. “As the first oral pen approved in the US, Orlynvah offers an excellent alternative treatment option for eligible patients in the underserved UUTI market.”

Concerns about empiric treatment, inappropriate use

The approval comes 3 years after the FDA rejected Iterum’s new drug application (NDA) for Orlynvah. Center he said again at that time more data were needed to support approval and to recommend at least one additional adequate and well-controlled trial. Iterum resubmitted an NDA, with data from the REASSURE trial, in April.

At a meeting of the FDA’s Antimicrobial Drug Advisory Committee on September 10, committee members agreed that Orlynvah could be beneficial for some patients, but some expressed concern that off-label use could foster antibiotic resistance. carbapenems, closely related to penems and essential. a class of antibiotics for serious, multidrug-resistant infections. That concern was shared by the FDA.

“While oral penem for the treatment of resistant bacteria that cause UUTI may be able to address an unmet need, its use in the ambulatory setting where treatment is often intensive raises concerns about inappropriateness. use that may contribute to AMR [antimicrobial resistance],” the agency said a short document.

The FDA added that careful antimicrobial stewardship and consideration by guideline committees “are needed to ensure that appropriate levels of sulopenem etzadroxil/probenecid remain at the top of treatment options for uUTI.”

The advisory committee did not vote on the recommendation.

A common infection in women

UUTIs are one of the most common infections experienced by women, accounting for nearly 40 million antibiotic prescriptions each year in the United States alone. It is estimated that 50% of all women have at least one UTI in their lifetime.

As the first oral pen approved in the US, Orlynvah offers an excellent alternative treatment option for eligible patients in the underserved UTI market.

To a presentation today for investors, company officials said that the four leading oral antibiotic treatments for UTI account for nearly 75% of the prescription market but have resistance rates near or above 20% and have additional safety concerns. It also noted that approximately 5% of SURE-1 patients had organisms that were resistant to all available oral antibiotics.

FDA team complete instructions information states that Orlynvah should only be used to treat UUTI that is proven or strongly suspected to be caused by susceptible bacteria. The drug is not approved as first-line or second-line treatment for complicated UTIs or complicated gastrointestinal infections.