A New Drug Application (NDA) for ceftobiprole was accepted for 3 indications including S aureus bacteremia, days after phase 3 results were published.
The FDA's acceptance of the New Drug Application (NDA) for ceftobiprole, submitted in August, could signifies a significant step forward in addressing severe bacterial infections.
Ceftobiprole was designated as a candidate for the US Generate Antibiotics Incentives Now (GAIN) Act, which facilitates the development of new antimicrobial drugs.
Ceftobiprole demonstrated noninferiority to daptomycin in phase 3 trial.
A New Drug Application (NDA) for ceftobiprole for 3 severe infection indications was accepted by the FDA on October 2, just days after publication of results from a phase 3 trial of its use to treat complicated Staphyloccus aureus bacteremia (SAB).
"We are pleased with the FDA's acceptance of our New Drug Application, which is another important step towards bringing ceftobiprole to patients with severe bacterial infections in the US, as there is a high medical need for new antibiotic treatment options, especially in complicated SAB," stated Marc Engelhardt, MD, chief medical officer, Basilea Pharmaceutica.
The NDA filed with the FDA in August, is for SAB, including right-sided infective endocarditis; acute bacterial skin and skin structure infections; and community-acquired bacterial pneumonia. The FDA has set April 3, 2024 as the Prescription Drug User Fee Act (PDUFA) goal date.
While this "advanced generation" cephalosporin is investigational in the US, it has been available in several countries in Europe, under the trade names Zevtera and Mabelio. It is the active moiety of the prodrug, ceftobiprole medocaril, which has also been available outside the US. Ceftobiprole was designated a candidate for the US Generate Antibiotics Incentives Now (GAIN) Act, established to facilitate development of new antimicrobials, and so would be eligible for ten years of market exclusivity in the US if approved.
Results from the phase 3, double-blind ERADICATE trial were published in The New England Journal of Medicine. The trial established noninferiority of ceftobiprole relative to daptomycin for treating complicated SAB, including in patients with right-sided endocarditis.
The trial randomized 390 patients to either ceftobiprole (n=189) 500mg intravenously every 6 hours for 8 days, and every 8 hours thereafter; or to daptomycin (n=198) 6 to 10mg/kg body weight every 24 hours (plus optional astreonam at the discretion of the treating clinicians).Patients were not eligible for the trial if they had unremovable endovascular prosthetic material, pneumonia, and those receiving potentially effective antibiotics for more than 48 hours within 7 days before randomization in the absence of persistent SAB.
The primary outcome was overall treatment success at 70 days after randomization; defined as survival, bacteremia clearance, symptom improvement, no new S aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics.
Treatment success was achieved in 69.8% of the ceftobiprole group and 68.7% of those treated with daptomycin. The adverse events were also similar, reported in 63.4% of those in the ceftobiprole group and 59.1% with daptomycin. Severe adverse events were reported in 18.8% and 22.7% of the groups, respectively. Gastrointestinal adverse events, primarily mild nausea, were more frequent with ceftobiprole.
The finding of noninferiority remained consistent among key subgroups, including patients with either methicillin-resistant S aureus (MRSA) or methicillin-susceptible S aureus (MSSA).
"In addition, microbiologic eradication, relapse of bacteremia, and new or worsening SAB complications were similar in the two trial groups, findings that further indicate that ceftobiprole was not less effective than daptomycin," reported Thomas Holland, MD, Division of Infectious Diseases, Duke University and Duke Clinical Research Institute, Durham, NC, and colleagues.
