Iterum plans to resubmit a New Drug Application for oral sulopenem for the treatment of patients with uUTi in Q2 of 2024.
The phase 3 REASSURE trial (NCT05584657) achieved noninferiority for its primary end point of overall response and demonstrated statistical superiority with oral sulopenem (sulopenem etzadroxil combined with probenecid in a bilayer tablet) vs oral amoxicillin/clavulanate (augmentin) in women with uncomplicated urinary tract infections (uUTIs), according to a news release from Iterum Therapeutics, the developer of the therapy.1
"We are very pleased to announce positive data from this confirmatory trial, which was conducted under special protocol assessment agreement with the U.S. Food and Drug Administration," said Corey N. Fishman, Iterum's CEO, in the news release.1
Data from the study showed that overall response, defined as the combined clinical cure plus microbiologic eradication, 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, 0.3-13.0).The difference reached statistical significance, indicating statistical superiority of oral sulopenem compared with amoxicillin/clavulanate.
Further, clinical success (defined as symptom resolution and no new uUTI symptoms) was achieved in 77.3% of patients in the oral sulopenem arm, compared with 76.7% of patients in the amoxicillin/clavulanate arm (treatment difference, 0.6; 95% CI, -4.8-6.1). Microbiological success (defined at eradication of qualifying uropathogen to less than 103 CFU/mL at the test-of-cure [TOC] visit) was achieved in 75.2% of patients in the oral sulopenem cohort vs 66.7% of patients in the amoxicillin/clavulanate cohort (treatment difference, 8.5; 95% CI, 2.6-14.3).
"In addition to achieving non-inferiority for the primary end point of overall response at the TOC visit in the Augmentin-susceptible population in the REASSURE trial, the lower limit of the 95% confidence interval around the treatment difference was above zero, indicating statistical superiority of oral sulopenem over Augmentin for the treatment of uUTI. Furthermore, consistent results were observed for all key secondary efficacy end points in this population," said Iterum's Chief Medical Officer Sailaja Puttagunta, MD, in the news release.1
Regarding safety, treatment was generally well-tolerated in both study groups. Less than 1% of patients on both regimens discontinued treatment due to adverse events. No serious adverse events (SAEs) were observed among patients in the oral sulopenem arm, compared with 5 SAEs experienced by patients in the amoxicillin/clavulanate arm. The investigators believe that no SAEs were related to study treatment.
Further, no new safety signals with oral sulopenem were observed. The overall safety profile for the therapy was consistent with that of previous phase 3 studies.
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 TOC visit (day 12) among patients in the microbiological-modified-intent-to-treat susceptible population.2
Puttagunta continued, "These results bring us one step closer to delivering a much-needed oral treatment option for women suffering from uUTIs. In addition, we believe these results, along with evidence from our prior phase 3 studies, support the potential of sulopenem in other indications, such as complicated urinary tract infections."1
According to the news release, Iterum plans to present completed data from the trial at an upcoming scientific meeting.
Fishman added, "With the positive data from this trial, we plan to resubmit our New Drug Application (NDA) for oral sulopenem for the treatment of uUTI in the second quarter of 2024. At the same time, with these results in hand, we will be focusing on a strategic process to sell, license, or otherwise dispose of our rights to sulopenem with the goal of maximizing value for our stakeholders. We believe there is tremendous value in sulopenem as a potential new, oral antibiotic for the uUTI indication which has over 30 million infections annually in the US, rising resistance to all currently prescribed oral antibiotics, and a complete lack of new product innovation over the last 20 years."1
Iterum expects an FDA response to their resubmitted NDA in Q4 of 2024.
1. Iterum Therapeutics announces positive topline results from its phase 3 REASSURE clinical trial of oral sulopenem in uncomplicated urinary tract infections. News release. Iterum Therapeutics plc. January 30, 2024. Accessed January 31, 2024. https://www.prnewswire.com/news-releases/iterum-therapeutics-announces-positive-topline-results-from-its-phase-3-reassure-clinical-trial-of-oral-sulopenem-in-uncomplicated-urinary-tract-infections-302047483.html
2. Oral sulopenem versus amoxicillin/clavulanate for uncomplicated urinary tract infection in adult women (REASSURE). ClinicalTrials.gov. Last updated October 27, 2023. Accessed January 31, 2024. https://clinicaltrials.gov/study/NCT05584657