Cefepime-taniborbactam is currently under review by the FDA for cUTI, including acute pyelonephritis, based on data from the CERTAIN-1 trial.
Data from the phase 3 CERTAIN-1 trial (NCT03840148) have been published in the New England Journal of Medicine as the FDA weighs a potential approval for cefepime–taniborbactam for the treatment of patients with complicated urinary tract infections (cUTIs), including acute pyelonephritis.1,2
Overall, the study demonstrated the superiority of cefepime-taniborbactam over meropenem in this patient population, with comparable safety profiles between both treatments.
Cefepime-taniborbactam is currently under review by the FDA for cUTI, including acute pyelonephritis. The FDA granted a priority review designation to a new drug application for the treatment in August 2023 based on findings from the CERTAIN-1 trial.3 The Prescription Drug User Fee Act (PDUFA) target action date is set for February 22, 2024.
“Gram-negative infections such as cUTI have become increasingly difficult to treat due to acquired bacterial resistance to multiple classes of antibiotics. Cefepime-taniborbactam has the potential to treat a broad range of patients with cUTI due to suspected or confirmed multidrug-resistant (MDR) pathogens including Enterobacterales and Pseudomonas aeruginosa,” said co-author Paul C. McGovern, MD, senior vice president at Venatorx, in a news release on the findings.2 “This phase 3 study is the culmination of a long journey of discovery and development, and we look forward to progressing this agent through the next regulatory stages so that the drug may reach patients world-wide as expeditiously as possible.”
In the CERTAIN-1 trial, cefepime–taniborbactam met the study’s primary end point by demonstrating a composite microbiologic and clinical response rate of 70.6% vs 58.0% with meropenem at the test of cure (TOC) visit (day 19-23).
A prespecified superiority analysis confirmed that cefepime–taniborbactam was statistically superior to meropenem for the composite end point (response rate difference, 12.6%; 95% CI, 3.1-22.2; P = .009) and for the microbiologic end point (response rate difference, 11.7%; CI, 2.9-21.0). The clinical end point response rate difference was 4.5% (CI, -2.6-12.6).
At the late follow-up visit (day 28-35), cefepime–taniborbactam demonstrated sustained superiority over meropenem in regard to the composite end point—with a response rate of 63.8% compared with 51.7% with meropenem (response rate difference, 12.1%; CI, 2.2-21.9) —as well as for the clinical end point (response rate difference, 9.9%; CI, 1.5-18.8). The microbiologic end point response rate difference was 7.7% (CI, -1.6-17.3).
Cefepime–taniborbactam also showed a numerical advantage to meropenem against resistant pathogens. With cefepime-resistant pathogens, cefepime–taniborbactam showed a response rate of 71%, compared with 53% with meropenem. Against ESBL-producing pathogens, the response rate for cefepime–taniborbactam was 71% vs 55% for meropenem. Against MDR pathogens, the response rate for cefepime–taniborbactam was 68%, compared with 60% with meropenem.
Regarding safety, the 2 treatments were similar, and data for cefepime–taniborbactam were consistent with historical safety data for cefepime. Among all patients, 2.0% of patients in the cefepime–taniborbactam arm experienced a serious adverse event vs 1.8% in the meropenem arm.
Treatment-emergent adverse events (TEAEs) occurred in 35.5% of patients who received cefepime–taniborbactam compared with 29.0% of patients who received meropenem. The most commonly reported TEAEs were headache (6.1% with cefepime–taniborbactam vs 3.7% with meropenem), diarrhea (4.1% vs 2.3%) and constipation (3.2% vs 1.4%). Treatment discontinuations due to a TEAE occurred in 3.0% of patients in the cefepime–taniborbactam arm and 0.9% of patients in the meropenem arm.
In total, the randomized, multicenter, double-blind, active-controlled, non-inferiority phase 3 CERTAIN-1 trial included 661 hospitalized adult patients with cUTI and acute pyelonephritis, including those with bacteremia. Patients received either 2.5 g cefepime–taniborbactam or 1 g meropenem every 8 hours for 7 days. The primary end point for the trial was the combined microbiologic and clinical response (composite success) at the TOC visit (day 19-23) in the microbiological intent-to-treat population (n = 436).
References
1. Wagenlehner FM, Gasink LB, McGovern PC, et al. Cefepime–taniborbactam in complicated urinary tract infection. N Engl J Med. 2024;390(7):611-622. doi:10.1056/NEJMoa2304748
2. New England Journal of Medicine publishes positive results of cefepime-taniborbactam from phase 3 CERTAIN-1 study of patients with complicated urinary tract infection. News release. Venatorx Pharmaceuticals. Published online and accessed February 20, 2024. https://venatorx.com/press-releases/new-england-journal-of-medicine-publishes-positive-results-of-cefepime-taniborbactam-from-phase-3-certain-1-study-of-patients-with-complicated-urinary-tract-infection/
3. Venatorx Pharmaceuticals Announces FDA Acceptance and Priority Review of New Drug Application for Cefepime-Taniborbactam to Treat Complicated Urinary Tract Infections (cUTI), including Pyelonephritis, in Adults. News release. Venatorx Pharmaceuticals. August 15, 2023. Accessed February 20, 2024. https://venatorx.com/press-releases/venatorx-pharmaceuticals-announces-fda-acceptance-and-priority-review-of-new-drug-application-for-cefepime-taniborbactam-to-treat-complicated-urinary-tract-infections-cuti-including-pyelonephritis/
AUGS Position Statement: Vaginal Pessary Use and Management for Pelvic Organ Prolapse
February 19th 2024The purpose of this clinical consensus statement is to identify areas of expert consensus and nonconsensus regarding pessary fitting, follow-up, and management of pessary complications to improve the safety and quality of care where evidence is currently limited.