FDA Approves Oral Sulopenem Etzadroxil and Probenecid (Orlynvah) for Uncomplicated UTIs
Key Insights
The FDA has approved sulopenem etzadroxil and probenecid (Orlynvah) for uncomplicated urinary tract infections (search) (uUTIs) in adult women with limited oral antibacterial options.
The approval was based on the SURE 1 trial, where sulopenem etzadroxil and probenecid showed superiority to ciprofloxacin in overall response rates.
The REASSURE study demonstrated non-inferiority of sulopenem etzadroxil and probenecid compared to amoxicillin and clavulanic acid for uUTI treatment.
The FDA has granted approval to sulopenem etzadroxil and probenecid (Orlynvah; Iterum Therapeutics (search)) for treating uncomplicated urinary tract infections (search) (uUTIs) caused by Escherichia coli (search), Klebsiella pneumoniae (search), or Proteus mirabilis (search) in adult women who have limited or no alternative oral antibacterial treatment options. This approval marks a significant advancement in addressing antimicrobial resistance and providing a new treatment modality for uUTIs.
Clinical Trial Data
The approval is supported by data from the SURE 1 and REASSURE clinical trials. The SURE 1 trial (NCT03354598) was a randomized, multicenter, double-blind study comparing oral sulopenem etzadroxil and probenecid to oral ciprofloxacin. Patients were randomized in a 1:1 ratio to receive either sulopenem etzadroxil and probenecid twice daily for 5 days or ciprofloxacin twice daily for 3 days. The primary endpoint was overall response.
Results from the SURE 1 trial demonstrated that sulopenem etzadroxil and probenecid was superior to ciprofloxacin, with overall response rates of 62.6% and 36%, respectively. However, in susceptible populations, sulopenem etzadroxil and probenecid was not non-inferior to ciprofloxacin, with response rates of 66.8% and 78.6%, respectively. A notable adverse event was diarrhea, reported more frequently with sulopenem etzadroxil and probenecid (12.4%) compared to ciprofloxacin (2.5%).
The REASSURE study was a randomized, multicenter, double-blind trial comparing sulopenem etzadroxil and probenecid to amoxicillin and clavulanic acid. The study showed non-inferiority of sulopenem etzadroxil and probenecid, with an overall response rate of 61.7% compared to 55% for amoxicillin and clavulanic acid. Clinical success rates were 77.3% for sulopenem etzadroxil and probenecid and 76.7% for amoxicillin and clavulanic acid, while microbiological success rates were 75.2% and 66.7%, respectively.
Expert Commentary
"Orlynvah offers new hope for patients suffering from difficult-to-treat uUTIs," said Corey Fishman, CEO of Iterum. "The introduction of novel products, like Orlynvah, is an important way to combat antimicrobial resistance to other approved oral agents and offers a potential solution to patients and physicians. As the first oral penem approved in the US, Orlynvah offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market."
Dr. Marjorie Golden, site chief of infectious disease at St. Raphael Campus Yale New Haven Hospital, added, "The FDA approval of Orlynvah is tremendous news for those of us who have been hoping for a new option to treat appropriate at-risk patients suffering from UTIs. Based on the totality of clinical data generated, Orlynvah has the potential to be an important treatment alternative for use in the community."