FDA approves cefepime/enmetazobactam for complicated UTI

The FDA has approved cefepime/enmetazobactam (Exblifep) for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, according to a news release from Allecra Therapeutics, who maintains sole responsibility for the therapy.¹

In addition to the FDA approval, Allecra’s commercial partner, Advanz Pharma, has submitted an application for Marketing Authorization Approval for cefepime/enmetazobactam in Europe.

In addition to the approval, the FDA has also granted Allecra a 5-year marketing exclusivity extension for cefepime/enmetazobactam as part of the Generating Antibiotic Incentives Now Act (GAIN Act). The GAIN Act provides benefits to manufacturers of Qualified Infectious Disease Products as a way to incentivize the creation of new anti-infective therapeutics.

"Receiving FDA approval is a tremendous achievement for Allecra and a testament to the hard work and dedication of a small, yet highly focused team of individuals. I extend my sincere congratulations to my colleagues Omar Lahlou and Patrick Velicitat for their leadership and oversight throughout this whole process,” said Iain Buchanan, supervisory board member of Allecra Therapeutics, in the news release.¹ “As we continue our discussions with strategic partners for product launch in the US, we value the FDA’s positive decision on Exblifep’s ability to address a critical unmet medical need for patients.”

The FDA approval is supported by data from the phase 3 ALLIUM trial (NCT03687255), which demonstrated the non-inferiority and superiority of cefepime/enmetazobactam vs piperacillin/tazobactam in regard to the primary composite outcome measure of clinical cure and microbiological eradication in patients with cUTIs.^2,3

Overall, clinical cure and microbiological eradication at the test-of-cure visit was achieved in 79.1% of patients who received cefepime/enmetazobactam, compared with 58.9% of patients who received piperacillin/tazobactam (between group difference, 21.2%; 95% CI, 14.3% to 27.9%). This difference met the prespecified noninferiority margin of -10%, as well as the criterion for superiority.

The study also included 20.9% of patients who had an extended spectrum beta-lactamases-producing baseline pathogen. Among those, 73.7% of patients in the cefepime/enmetazobactam arm achieved the composite outcome vs 51.5% of those in the piperacillin/tazobactam arm (difference, 30.2%; 95% CI, 13.4% to 45.1%).

Regarding safety, 50.0% of patients who received cefepime/enmetazobactam experienced a treatment-emergent adverse event (TEAE), compared with 44.0% in patients who received piperacillin/tazobactam. Overall, the majority of TEAEs were mild to moderate in severity (89.9% and 88.6%, respectively). Treatment discontinuation due to AEs occurred in 1.7% of patients in the cefepime/enmetazobactam arm and 0.8% of patients in the piperacillin/tazobactam arm.

In total, the randomized, double-blind, active-controlled, multicenter, noninferiority clinical trial included 1041 patients across 90 sites in Europe, North and Central America, South America, and South Africa. Patients were randomly assigned to receive 2 g cefepime/0.5 g enmetazobactam (n = 520) or 4 g piperacillin/0.5 g tazobactam (n = 521) by 2-hour infusion every 8 hours for 7 days (up to 14 days among patients with a positive blood culture at baseline).

The primary outcome measure was the proportion of patients in the primary analysis set who achieved overall treatment success, defined as the clinical cure plus microbiological eradication, at the test-of-cure visit.

In addition to the FDA approval, Allecra’s commercial partner, Advanz Pharma, has submitted an application for Marketing Authorization Approval for cefepime/enmetazobactam in Europe.

References

1. Allecra Therapeutics announces U.S. FDA approval for EXBLIFEP for the treatment of complicated urinary tract infections. News release. Published online and accessed February 27, 2024. https://www.businesswire.com/news/home/20240227132611/en/Allecra-Therapeutics-Announces-U.S.-FDA-Approval-for-EXBLIFEP%C2%AE-for-the-Treatment-of-Complicated-Urinary-Tract-Infections

2. Kaye KS, Belley A, Barth P, et al. Effect of cefepime/enmetazobactam vs Piperacillin/tazobactam on clinical cure and microbiological eradication in patients with complicated urinary tract infection or acute pyelonephritis: a randomized clinical trial. JAMA. 2022;328(13):1304-1314. doi:10.1001/jama.2022.17034

3. Allecra Therapeutics publishes final phase 3 ALLIUM data in JAMA:cefepime/enmetazobactam met criteria for superiority. News release. Allecra Therapeutics. Published online May 10, 2022. Accessed February 27, 2024. https://www.allecra.com/