Sulopenem is Noninferior to Amoxicillin/Clavulanate For Uncomplicated UTIs

Image credit: Interum Therapeutics

A newer FDA approved antibiotic, sulopenem (Orlynvah), was found to be noninferior to a long-standing treatment, amoxicillin/clavulanate (Augmentin), in adult women with uUTIs, according to data from the REASSURE phase 3 trial. The results were published in the NEJM Evidence journal.¹

“Overall success in the microbiologic-modified intent-to-treat population occurred in 318 of 522 (60.9%) participants treated with sulopenem versus 260 of 468 (55.6%) participants treated with amoxicillin/clavulanate (difference, 5.4 percentage points; 95% confidence interval [CI], −0.8 to 11.5), meeting criteria for noninferiority,” the investigators wrote.¹

Iterum Therapeutics developed sulopenem—its first compound—which is a novel penem anti-infective compound, with an oral formulation and IV formulation. “We are very pleased that NEJM Evidence have published the results from the REASSURE trial,” Iterum CEO Corey Fishman, said in a statement. “This article highlights the need for new antibiotics, like Orlynvah, for the treatment of uUTI given the increasing rates of multidrug resistance to the currently available antibiotics. We expect Orlynvah to be available to treat women with hard-to-treat infections in the next quarter.”²

The REASSURE trial included 2222 adult women with uUTIs and the median age was 51 years. Participants were randomly assigned to receive either treatment for 5 days. The trial's primary endpoint was the overall response rate at the test-of-cure visit. ¹

In terms of adverse events, there were more experienced in the sulopenem group. “Treatment-emergent adverse events occurred more frequently with sulopenem compared with amoxicillin/clavulanate, including diarrhea (8.1% vs. 4.1%), nausea (4.3% vs. 2.9%), and headache (2.2% vs. 1.5%),” the investigators wrote.¹

Antibiotic Resistance Data in the Trial

UTIs are among the most common infections encountered. There are approximately 15 million emergency room and office visits for symptoms of UTIs and over 40 million total prescriptions for uUTIs in the US annually, with approximately two-thirds or 26 million of those prescriptions written for patients that are at elevated risk for treatment failure, based on market research.²

Resistance was also seen in the REASSURE trial. “Ninety-one (9.2%) patients in the primary population (microbiologic-modified intent-to-treat population), the combined population of patients with a positive baseline urine culture and without regard to amoxicillin/clavulanate susceptibility, had a baseline pathogen resistant to three or more classes of antibiotics,” the investigators wrote.¹

Learn more: Antibiotic Resistance in the Context of UTI Treatment Developments

FDA Approval

Oral sulopenem from Iterum Therapeutics was FDA approved last fall for uUTIs in adult women caused by specific bacteria, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, when there are limited or no alternative oral antibiotic options.

“As the first oral penem approved in the US, Orlynvah offers an excellent alternative treatment option for appropriate patients in the underserved uUTI market. With FDA approval and a clear label, we will renew our efforts to achieve a strategic transaction involving Orlynvah with the goal of maximizing value for our stakeholders,” Fishman said in a statement at the time of the approval.³

References
1. Puttagunta S, Aronin SI, Gupta J, Das AF, Gupta K, Dunne MW. Sulopenem versus Amoxicillin/Clavulanate for the Treatment of Uncomplicated Urinary Tract Infection. NEJM Evid. 2025;4(7):EVIDoa2400414. doi:10.1056/EVIDoa2400414
2. Iterum Therapeutics Announces Publication of REASSURE Trial in NEJM Evidence. Iterum press release. June 25, 2025. Accessed June 25, 2025.
3.Iterum Therapeutics receives U.S. FDA approval of ORLYNVAH (oral sulopenem) for the treatment of uncomplicated urinary tract infections. News release. Iterum Therapeutics. October 25, 2024. Accessed June 25, 2025. https://www.iterumtx.com/news/press-releases/detail/136/iterum-therapeutics-receives-u-s-fda-approval-of