On October 16th, 2019, the Antimicrobial Drugs Advisory Committee (AMDAC) reviewed the New Drug Application (NDA) 209445 for cefiderocol lyophilized powder (Shionogi Inc.) for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis due to gram-negative bacteria in patients with limited or no alternative treatment options.
FETROJA is a cephalosporin antibacterial drug product consisting of cefiderocol sulfate tosylate for intravenous infusion. Like the other cephalosporins, it penetrates the outer cell membrane of gram-negative pathogens and binds to penicillin-binding proteins to inhibit cell wall synthesis. Cefiderocol’s unique siderophore structure both enhances its membrane permeability and increases stability against lactamases.
As evidence, Shionogi Inc. presented the results from a pivotal phase-III study and an open-label study. APEKS-cUTI study, a multinational, multicenter, double-blind clinical trial,evaluated the efficacy and safety of FETROJA versus imipenem/cilastatin (IPM/CS) in patients with cUTI. The open-label CREDIBLE-CR study evaluated the new drug against best available therapy in 150 patients with serious gram-negative infections involving nosocomial pneumonia, sepsis, or drug-resistant cUTI.
This meeting consisted of 1 discussion question and 1 voting question. The voting question asked whether the Sponsor provided substantial evidence of efficacy and safety of cefiderocol for the proposed indication. The vote resulted in 14 YES, 2 NO, and 0 ABSTENTION.
The committee members in support of approval felt that the cUTI study was well designed and demonstrated meaningful effects. Those who opposed approval expressed concern that the open-label study found that cefiderocol was associated with an increased risk of mortality. Despite the approval, panelist consistently remarked on the need for further studies.
The agency is not obligated to follow its panel’s recommendation, yet normally does so, and did in this case.
On November 14th, 2019, the FDA gave cefiderocol an approval based on limited clinical safety and efficacy data for the treatment of patients 18 years of age or older with complicated urinary tract infections (cUTI), including kidney infections caused by susceptible gram-negative microorganisms, who have limited or no alternative treatment options. The FDA informed Shionogi that they are required to conduct further postmarketing safety surveillance including pediatric safety studies in accordance with the Pediatric Research Equity Act. The approval letter outlined the design and reporting requirements for each study.
ISS has two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact firstname.lastname@example.org.