FDA Sets Review Date for Combination Antibiotic for Complicated UTIs

FDA has accepted a new drug application (NDA) for cefepime-taniborbactam injection to treat adult patients with complicated urinary tract infections (cUTI), including patients who have pyelonephritis where the infection spreads to the kidneys. The FDA has granted Priority Review of the NDA with a Prescription Drug User Fee Act (PDUFA) target action date of Feb. 22, 2024.

Urinary tract infections are common, especially in women. But urinary infections in immunocompromised patients, mens, and those associated with fevers, stones, sepsis, urinary obstruction, catheters, or involving the kidneys are considered complicated infections. In the United States, there are more 626,000 hospital admissions a year for complicated urinary tract infections, a recent study found.

Cefepime, a fourth-generation cephalosporin, is a widely used beta-lactam antibiotic effective against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a beta-lactamase inhibitor. Together the two have the potential to treat patients with serious bacterial infections caused by antibiotic resistant gram-negative bacteria. Patients with carbapenem-resistant strains of Enterobacterales infections had longer hospital lengths of stay, were less likely to be discharged home, and had a higher readmission rate, finds a separate study.

The combination therapy was developed by Everest Medicines, which has partnered with Venatorx Pharmaceuticals.

Paul McGovern, M.D.

“Due to its broad spectrum of in-vitro activity against established and rapidly increasing mechanisms of carbapenem resistance such as serine- and metallo-beta-lactamases and the positive results demonstrated in CERTAIN-1, cefepime-taniborbactam, if approved, will address a critical unmet need and be a potentially essential treatment option in the continuing fight against antimicrobial resistance in gram-negative bacterial infections,” Paul McGovern, M.D., senior vice president, medical sciences at Venatorx, said in a press release.

The cefepime-taniborbactam NDA is supported by results from the pivotal phase 3 study, CERTAIN-1, evaluating the efficacy and safety of cefepime-taniborbactam compared with meropenem in adults with cUTI. The trial enrolled 661 adult patients, and cefepime-taniborbactam met the primary efficacy endpoint of statistical noninferiority to meropenem in the microITT population. Additionally, the combination was shown to be superior to meropenem when tested between day 19 to day 23. Clinical response was maintained at the follow-up up visit between day 28 and day 35.

Additionally, the study demonstrated that the combination was effective against extended spectrum beta-lactamase producing Enterobacterales and carbapenem-resistant Enterobacterales, which the CDC has classified as pathogens that represent urgent threats.

Cefepime-taniborbactam was well-tolerated. Rates of treatment-emergent adverse events (TEAEs) were 35.5% for cefepime-taniborbactam treated patients, and serious TEAEs occurred in 2% of patients. Treatment discontinuations due to treatment-related adverse events occurred in 3.0% of cefepime-taniborbactam patients.