The Food and Drug Administration (FDA) has granted approval for Orlynvah™ (sulopenem etzadroxil and probenecid) to treat uncomplicated urinary tract infections (uUTI) caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options.
Orlynvah is a bilayer tablet that combines sulopenem etzadroxil, a penem antibacterial drug, with probenecid, a renal tubular inhibitor. This treatment has been shown to be effective against third-generation cephalosporin-resistant Enterobacterales species.
The approval is based on findings from the phase 3 noninferiority trials, SURE 1 (ClinicalTrials.gov Identifier: NCT03354598) and REASSURE (ClinicalTrials.gov Identifier: NCT05584657). In these trials, oral sulopenem etzadroxil 500 mg/probenecid 500 mg taken twice daily for five days was compared with oral ciprofloxacin 250 mg twice daily for three days or amoxicillin 875 mg/clavulanate 125 mg twice daily for five days in adult women with uUTI.
In the SURE 1 trial (N=1660), treatment with sulopenem etzadroxil/probenecid showed superiority over ciprofloxacin in patients with ciprofloxacin-resistant infections, achieving a composite response rate (combining microbiological response and clinical cure) of 48.1%, compared to 32.9% in the ciprofloxacin group (treatment difference 15.3; 95% CI, 4.3-25.8; P = .006).
Similarly, in the REASSURE trial (N=2214), the sulopenem etzadroxil/probenecid treatment demonstrated superiority over amoxicillin/clavulanate in amoxicillin/clavulanate-susceptible patients, with a complete response rate of 61.7% compared to 55% in the amoxicillin/clavulanate group (treatment difference 6.7; 95% CI, 0.3-13.0).
However, in separate phase 3 clinical trials investigating sulopenem etzadroxil/probenecid as a step-down treatment for complicated urinary tract infections (ClinicalTrials.gov Identifier: NCT03357614) and complicated intra-abdominal infections (ClinicalTrials.gov Identifier: NCT03358576), Orlynvah did not show efficacy and is therefore not indicated for these infections.
As reported by empr, the most commonly reported adverse reactions associated with sulopenem etzadroxil/probenecid include diarrhea, nausea, vulvovaginal mycotic infections, headaches, and vomiting.
“Orlynvah offers new hope for patients suffering from difficult-to-treat uUTIs,” stated Corey Fishman, Iterum’s Chief Executive Officer. “The introduction of novel products like Orlynvah is crucial in combating antimicrobial resistance to other approved oral agents and provides a potential solution for patients and healthcare providers.”
Orlynvah is available as a tablet containing 500 mg of sulopenem etzadroxil and 500 mg of probenecid.