A new oral antibiotic has cracked the nod from the FDA for the treatment of uncomplicated urinary tract infections, despite the agency’s reviewers voicing ongoing concerns – before an Antimicrobial Drugs Advisory Committee meeting last month – about the benefits versus the risks of the treatment, including its potential for inappropriate use.
FDA advisers echoed these concerns, reports Medpage Today.
Nevertheless, approval has been granted for oral sulopenem etzadroxil and probenecid (Orlynvah) to treat uncomplicated UTIs caused by certain bacteria in women with limited or no alternative oral antibacterial treatment options, the agency said last week.
The drug is a combination of a penem antibacterial (sulopenem etzadroxil) and a renal tubular transport inhibitor (probenecid). It is indicated to treat UTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis, and is the first oral penem approved for use in the US, drugmaker Iterum Therapeutics said.
The treatment is not indicated for primary or step-down treatment of complicated UTI or complicated intra-abdominal infections, the FDA emphasised.
The agency’s decision was supported by two phase 3 non-inferiority trials: SURE-1, which compared the safety and efficacy of sulopenem etzadroxil/probenecid versus ciprofloxacin, and REASSURE, which compared it against amoxicillin/clavulanate.
In the SURE-1 study of 1 660 women with uUTI, sulopenem etzadroxil/probenecid showed a composite response rate (combined microbiological and clinical response) of 48% versus 33% in the ciprofloxacin group. In the REASSURE trial of 2 214 women, sulopenem etzadroxil/probenecid showed a composite response rate of 62% compared with 55% in the amoxicillin/clavulanate group.
Clinical trials evaluating the antibiotic in complicated UTI or complicated intra-abdominal infections did not demonstrate effectiveness, the FDA stated.
Sulopenem etzadroxil/probenecid is taken as one tablet twice daily for five days, with the most common adverse reactions seen in patients treated with the drug being diarrhoea, nausea, vulvovaginal mycotic infection, headache, and vomiting.
Prescribing information includes warnings for hypersensitivity reactions, Clostridioides difficile-associated diarrhoea, and potential exacerbation of gout.
The treatment is contra-indicated 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.
In 2021, the FDA rejected the oral antibiotic based on mixed data from another phase III trial and recommended that Iterum conduct an additional study. After completing REASSURE, the company resubmitted a new drug application in 2024.
Medpage Today article – FDA Approves Novel Treatment for UTIs (Open access)
See more from MedicalBrief archives:
Most women receive inappropriate treatment for uncomplicated UTIs
Rapid test to check antibiotic efficacy against urinary-tract bacteria
New drug combination highly effective against urinary tract infections – global trial
FDA approves new UTI treatment
ALTAR trial supports antibiotic alternative for recurrent urinary tract infections