FDA requests additional data regarding cefepime-taniborbactam for cUTI

The FDA has issued a complete response letter (CRL) to Venatorx Pharmaceuticals and Melinta Therapeutics regarding their new drug application (NDA) for cefepime-taniborbactam for the treatment of patients with complicated urinary tract infection (cUTI), including acute pyelonephritis caused by susceptible gram-negative microorganisms.¹

The NDA for cefepime-taniborbactam was granted a priority review designation by the FDA in August 2023.

The CRL requests additional chemistry, manufacturing, and controls (CMC) and related data about the drug, testing methods, and manufacturing process. The FDA did not identify any clinical or safety issues with the treatment, nor request any new clinical trials to support the approval of cefepime-taniborbactam.

“While we are disappointed with this setback, we maintain utmost confidence in cefepime-taniborbactam. We are already hard at work generating the additional requested CMC data, and we will continue to work closely with the FDA so that we can make this important new medicine available to patients as quickly as possible,” said CEO of Venatorx Pharmaceuticals Christopher J. Burns, PhD, in a news release on the announcement.¹

The NDA for cefepime-taniborbactam was granted a priority review designation by the FDA in August 2023.2 The application was supported by findings from the phase 3 CERTAIN-1 trial (NCT03840148), which were recently published in the New England Journal of Medicine.³

Overall, the study demonstrated the superiority of cefepime-taniborbactam over meropenem in patients with cUTI, with comparable safety profiles between both treatments.^3,4

In the 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).

The efficacy of cefepime-taniborbactam for the composite end point was sustained at the late follow-up visit conducted on days 28 to 35.

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 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).

Christine Ann Miller, CEO and president of Melinta Therapeutics, concluded in the news release, “We are committed to our plans of supporting the US commercialization of this drug, which we believe when approved, will offer healthcare providers an important therapy for adult patients suffering from complicated urinary tract infections including acute pyelonephritis caused by susceptible gram-negative microorganisms.”¹

References

1. Venatorx and Melinta provide update on status of U.S. new drug application for cefepime-taniborbactam. News release. Venatorx Pharmaceuticals. Published online and accessed February 23, 2024. https://www.businesswire.com/news/home/20240223169844/en/Venatorx-and-Melinta-Provide-Update-on-Status-of-U.S.-New-Drug-Application-for-Cefepime-Taniborbactam

2. 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 23, 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/

3. 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

4. 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. February 20, 2024. Accessed February 23, 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/