Iterum Therapeutics is awaiting a critical FDA decision regarding its new drug application (NDA) for oral sulopenem, a potential treatment for uncomplicated urinary tract infections (uUTIs) in adult women. The FDA's decision is expected by October 25, marking a pivotal moment for the company and the future of antibiotic therapies.
The Antimicrobial Drugs Advisory Committee (AMDAC) convened on September 9 to discuss the benefits, risks, and appropriate use of sulopenem etzadroxil/probenecid. While the committee acknowledged oral sulopenem as an important treatment option for certain uUTI patients, particularly those with multi-drug resistant pathogens, concerns were raised about the potential for misuse and the subsequent acceleration of antibiotic resistance.
Addressing Unmet Needs in uUTI Treatment
Uncomplicated UTIs are common bacterial infections, especially among women. Current treatment options are increasingly limited due to rising antimicrobial resistance. Oral sulopenem, if approved, could become the first oral penem antibiotic in the U.S., offering a new approach to combat resistant infections in community settings. Data supporting the NDA included results from the Phase 3 REASSURE and SURE-1 clinical trials.
The Phase 3 REASSURE trial compared oral sulopenem to Augmentin (amoxicillin/clavulanate). Results indicated non-inferiority from sulopenem when compared to Augmentin, with a treatment difference of 6.7% for overall response, 0.6% for clinical success, and 8.5% for microbiological success. These rates were 61.7%, 77.3%, and 75.2%, respectively for sulopenem and 55%, 76.7%, and 66.7%, respectively for Augmentin.
Concerns and Mitigation Strategies
Despite the potential benefits, AMDAC members voiced concerns about the drug's potential for misuse, which could exacerbate antibiotic resistance. The committee emphasized the need for clear labeling and dosage specifications to guide responsible prescription. Suggestions included limiting use to cases where culture results confirm resistance to other treatment options and implementing pack sizes that align with treatment courses.
"The positioning comes down to only using it [oral sulopenem] when it is really needed," said Hazel Parker, an honorary clinical senior research fellow at the University of Exeter, UK. "For example, this can be based on culture results that show resistance to other treatment options. Pack sizes that mirror treatment courses could also be beneficial."
Iterum's CEO, Corey Fishman, acknowledged the importance of appropriate use, stating that it is "critical to limiting antimicrobial resistance." The company suggested that prior authorizations by insurance companies could help curb misuse, though this approach was met with skepticism from some public health advocates.
The Role of Antibiotic Stewardship
The broader issue of antibiotic stewardship was a key theme throughout the advisory committee meeting. Members highlighted the need for post-marketing surveillance to monitor the drug's impact on resistance patterns and refine its label accordingly. They also stressed the importance of public-private cooperation in addressing antibiotic resistance, citing Merck's support of the Study for Monitoring Antimicrobial Resistance Trends (SMART) initiative as a positive example.
Dr. Lindsey R. Baden, the acting AMDAC chairperson, emphasized that all available post-marketing surveillance tools will be essential for the antibiotic’s use as this is a dynamic problem.
If approved, oral sulopenem could offer a valuable new treatment option for uUTIs, particularly in the face of rising antibiotic resistance. However, its successful integration into clinical practice will depend on careful stewardship, responsible prescribing, and ongoing monitoring of its impact on antimicrobial resistance.
