Cefepime-taniborbactam trumps meropenem for complicated UTI

Cefepime-taniborbactam (FTB) is significantly better than meropenem for the treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP), according to results of the Cefepime Rescue with Taniborbactam in cUTI (CERTAIN-1) study presented at the recent ID Week 2022.

CERTAIN-1 was a randomized, double-blinded, and double-dummied phase III study that compared FTB to meropenem in 661 adults hospitalized for cUTI or AP. FTB was given at 2.5-g doses intravenously every 8 hours, while meropenem was administered intravenously at a 1-g dose every 8 hours. Interventions lasted for 7 days with the possibility of extending to 14 days for patients with bacteraemia.

Of the 661 participants, 66.0 percent (n=436) had sufficient data to be included in the micro-intention-to-treat population. AP was diagnosed in 42.2 percent, while 57.8 percent had cUTI and 13.1 percent had bacteraemia. The primary outcome was a composite of microbiologic and clinical response, which occurred at a much higher rate in those treated with FTB vs meropenem (70.0 percent vs 58.0 percent). [IDWeek 2022, abstract 731]

When assessed at 7–14 days following treatment, FTB led to a comparable response rate as meropenem (88.7 percent vs 86.0 percent; treatment difference, 2.7 percent, 95 percent confidence interval [CI], –3.6 to 10.1).

However, at the test-of-cure visit (day 19–23), FTB was found to be statistically better than meropenem in terms of the primary outcome (treatment difference, 11.9 percent, 95 percent CI, 2.4–21.6; p=0.0136). FTB remained significantly superior to meropenem until the late follow-up visit at 28–35 days after the intervention (treatment difference, 11.7 percent, 95 percent CI, 1.9–21.5; p=0.019).

Subgroup and stratified analyses did not attenuate the principal findings.

With regard to safety, 35.5 percent of FTB-treated patients experienced treatment-emergent adverse events, as opposed to 29.0 percent of meropenem counterparts. Serious side effects arose in 2.0 percent and 1.8 percent of the treatment arms, respectively. The most common toxicities were headache (6.1 percent in FTB, 3.7 percent in meropenem) and diarrhoea (4.1 percent in FTB, 2.3 percent in meropenem).

FTB is an investigational antimicrobial agent comprised of the combination of beta-lactam and beta-lactamase inhibitors. In laboratory studies, FTB has shown activity against Pseudomonas aeruginosa and the Enterobacterales order.

“Carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa are global antimicrobial resistant threats,” said the researchers, led by Paul C. McGovern, MD, the study’s presenting author and senior vice president of medical sciences at Venatorx Pharmaceuticals.

During the presentation at Virtual ID Week 2022, McGovern revealed that based on its success in CERTAIN-1, the company is looking to submit a new drug application for FTB to the United States Food and Drug Administration early next year.