Nabriva Therapeutics Receives CRL FDA Letter Delaying Approval

Ireland-based Nabriva Therapeutics announced it received a complete response letter (CRL) from the US Food and Drug Agency (FDA) regarding its anti-infective agent fosfomycin. The company is seeking FDA approval for injection for complicated urinary tract infections (cUTI), including acute pyelonephritis.

In the CRL, the FDA sited its inability to conduct inspections at the company’s manufacturing facilities due coronavirus 2019 (COVID-19)-related travel restrictions. The FDA also pointed out it was not looking for any additional data related to fosfomycin’s efficacy or safety.

The company did not make any public comments regarding the CRL. However, when the company announced its resubmission for a new drug application (NDA) back in January, the company did say in its announcement, “The NDA resubmission is supported by data from a pivotal Phase 2/3 clinical trial (known as ZEUS™), which met its primary endpoint of statistical non-inferiority to piperacillin/tazobactam in patients with cUTI, including acute pyelonephritis.”

Separately, fosfomycin’s efficacy in treating bacteremic urinary tract infections (BUTI) due to multidrug-resistant E. coli (MDREC) was reported by Contagion^® back in May. Specifically, the article reported that “fosfomycin is likely inferior to carbapenem or ceftriaxone for treating patients.”

In a study looking at the drug for that indication, 70% of the patients on fosfomycin reached clinical or microbiological cure (CMC), but 79.4% of patients on the comparator drugs reached CMC. Eight patients (14.2%) in the fosfomycin group suffered recurrence; compared to just 4 patients (6.6%) in the comparator group.

“Even if the calculated sample size would be achieved, it is improbable that fosfomycin could demonstrate to be non-inferior to carbapenem or ceftriaxone for CMC,” investigators concluded.

With drug resistance continuing to be a large problem in the medical community, clinicians are looking for therapies to add to the armamentariums.

A long established therapy discovered back in the 1960s, fosfomycin has been used outside the US for complicated urinary tract infections as well a variety of serious bacterial infections.

The FDA granted fosfomycin Qualified Infectious Disease Product (QIDP) and fast track designations for cUTIs and other serious infections.

Nabriva will request a Type A meeting with FDA to discuss the agency’s plans for completing manufacturing facility inspections.