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Published data show superiority of cefepime–taniborbactam over meropenem for cUTI

News
Article

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

Treatment-emergent adverse events (TEAEs) occurred in 35.5% of patients who received cefepime–taniborbactam compared with 29.0% of patients who received meropenem.

Treatment-emergent adverse events (TEAEs) occurred in 35.5% of patients who received cefepime–taniborbactam compared with 29.0% of patients who received meropenem.

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/

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