Oral sulopenem for uncomplicated urinary tract infection launches on US market

Sulopenem etzadroxil and probenecid (Orlynvah) oral tablets are now commercially available in the US for patients with uncomplicated urinary tract infections (uUTIs), Iterum Therapeutics announced in a news release.¹

Oral sulopenem was approved in the US in October 2024 for the treatment of uUTIs caused by the designated microorganisms Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis in adult women who have limited or no alternative oral antibacterial treatment options. With this approval, oral sulopenem became the first oral penem antibiotic approved for use in the US.

“Our mission is to create new antibiotics for patients and to be a treatment alternative to address substantial unmet medical needs in the community,” said Corey Fishman, CEO of Iterum Therapeutics, in the news release from the company.¹ “For many people with multidrug-resistant uUTIs, options have been exhausted. We’re proud to introduce ORLYNVAH—the first oral penem ever approved by the FDA—giving clinicians and patients a much-needed new therapy.”

In the news release, Iterum Therapeutics emphasized the need for effective oral therapies due to increasing rates of treatment resistance. The company cited a 2024 study of 150,000 patients with uUTIs, which found that 57% of initial infections were resistant to at least 1 antibiotic class, and 13% were resistant to 3 or more.

“For patients who currently have limited treatment options, ORLYNVAH provides a long overdue oral alternative that allows for treatment in the community,” explained Marjorie Golden, MD, FACP, AAHIVS, Site Chief, Infectious Disease, St. Raphael Campus Yale New Haven Hospital, in the news release.¹ “This paradigm shift in the management of patients with uUTI will not only reduce emergency department visits and hospital admissions, but it will also favorably impact patients’ quality of life.”

Data on Oral Sulopenem

The approval of oral sulopenem was supported by data from the phase 3 SURE 1 (NCT03366207) and REASSURE (NCT05584657) trials.

In SURE 1, oral sulopenem demonstrated superiority over ciprofloxacin in the treatment of patients with fluoroquinolone-resistant infections and non-inferiority to ciprofloxacin in the treatment of patients with a quinolone-susceptible uropathogens.

In total, the trial enrolled 1671 patients with uUTI who were randomly assigned 1:1 to receive oral sulopenem (n = 835) or ciprofloxacin (n = 836). Of those, 1071 were included in the microbiological-modified-intent-to-treat (micro-MITT) population. The quinolone-susceptible population (microMITT S) consisted of 370 patients in the sulopenem arm and 415 patients in the ciprofloxacin arm. The quinolone non-susceptible population (microMITT R) consisted of 147 patients in the sulopenem arm and 139 patients in the ciprofloxacin arm.

In the quinolone non-susceptible population, data showed an overall response rate (microbiological success plus clinical success) at the test of cure visit (day 12) of 62.6% among patients in the sulopenem arm vs 36.0% in the ciprofloxacin arm (difference, 26.6; 95% CI, 15.1 to 37.4; P < .001). In the quinolone-susceptible population, the overall response rate at the test of cure visit on day 12 was 66.8% in the sulopenem arm vs 78.6% in the ciprofloxacin arm (difference, -11.8; 95% CI, -18.0 to -5.6), which met the threshold for non-inferiority. The authors also noted, “The difference in outcome was a consequence of lower rates of asymptomatic bacteriuria in patients receiving ciprofloxacin.”

In the REASSURE trial, oral sulopenem demonstrated non-inferiority to oral amoxicillin/clavulanate in the treatment of patients with uUTI.

In total, the REASSURE trial included 2222 adult women who were randomly assigned 1:1 to receive oral sulopenem twice daily for 5 days or amoxicillin/clavulanate twice daily for 5 days. The primary end point for the study was overall response at the test-of-cure visit (day 12) among patients in the micro-ITT susceptible population.

Data from the trial showed that an overall response was achieved in 61.7% of patients who received oral sulopenem vs 55% of patients who received amoxicillin/clavulanate (treatment difference, 6.7; 95% CI, 0.3 to 13.0). Treatment was generally well-tolerated in both study arms, and no new safety signals were observed with oral sulopenem.

“The availability of ORLYNVAH is tremendous news for clinicians and patients alike,” Golden added in the news release.¹ “The launch of ORLYNVAH provides a new treatment option with impressive efficacy data to treat appropriate adult women suffering from difficult-to-treat uUTIs.”

REFERENCES

1. Iterum Therapeutics launches ORLYNVAH, the first and only oral penem antibiotic in the U.S. News release. Iterum Therapeutics. August 20, 2025. Accessed August 20, 2025. https://www.iterumtx.com/news/press-releases/detail/155/iterum-therapeutics-launches-orlynvah-the-first-and

2. Dunne MW, Das A, Akinapelli K, Zelasky MT, Boucher HW, Aronin AI. Efficacy and safety of oral sulopenem etzadroxil/probenecid versus oral ciprofloxacin in the treatment of uncomplicated urinary tract infections (uUTI) in adult women: Results from the SURE-1 trial. Presented at: ID Week 2020. October 21, 2020. Accessed August 20, 2025.https://d1io3yog0oux5.cloudfront.net/_c686b74a40042109ff06b21eccc8f678/iterumtx/db/395/2729/pdf/SURE+1+Slide+Presentation+IDweek+2020+19OCT_final.pdf