Iterum Therapeutics U.S. Ltd. – FDA CRL

The FDA issued a Complete Response Letter (CRL) to Iterum Therapeutics U.S. Ltd. regarding its New Drug Application (NDA 213972) for sulopenem etzadroxil and probenecid tablets, initially submitted on November 25, 2020. The agency determined that the application cannot be approved in its current form due to a lack of substantial evidence of effectiveness, citing insufficient clinical data as defined under 21 CFR §314.126 and §314.125(b)(5) of the Federal Food, Drug, and Cosmetic Act.

The primary violation was the inadequate clinical and statistical evidence for the proposed indication of treating adult women with uncomplicated urinary tract infections (uUTI). Despite some statistical significance in one study, the results were not sufficient as a single trial, and other studies failed to meet their primary endpoints. The FDA recommends conducting at least one additional adequate and well-controlled uUTI study, potentially with a different comparator drug and further investigation into optimal dosing.

Additional required actions include comprehensive revisions to container labels and carton labeling to ensure consistency with prescribing information, inclusion of linear barcodes on bottle labels, blister cells, and carton labeling, and proper placement of human-readable and machine-readable product identifiers, all in accordance with 21 CFR 201.25. Iterum Therapeutics must also provide a detailed safety update, including all new nonclinical and clinical safety data, and resubmit the proposed proprietary name, Orlynvah, once these deficiencies are addressed.