Originally published by our sister publication Infectious Disease Special Edition

By IDSE News Staff

The FDA approved ceftobiprole medocaril sodium for injection (Zevtera, Basilea Pharmaceutica International) for three different indications.

Ceftobiprole medocaril is indicated for the treatment of adults with bacteremia caused by Staphylococcus aureus, including those with right-sided infective endocarditis, adults with acute bacterial skin and skin structure infections (ABSSSI), and adults and children 3 months to 17 years old with community-acquired bacterial pneumonia (CABP).

The New Drug Application (NDA) was supported by three phase-3 studies.

The efficacy of ceftobiprole medocaril for bacteremia was evaluated in a randomized, controlled, double-blind, multinational, multicenter ERADICATE trial. Researchers randomly assigned 390 patients to receive ceftobiprole medocaril (192 subjects) or daptomycin plus optional aztreonam (198 subjects). The primary measure of efficacy was overall success (defined as survival, symptom improvement, S. aureus bacteremia bloodstream clearance, no new S. aureus bacteremia complications and no need for alternative antibiotics) at the post-treatment evaluation visit, which occurred 70 days after random assignment of an antibiotic. 

A total of 69.8% of patients who received ceftobiprole medocaril achieved overall success compared with 68.7% of those who received the comparator.

“There is a high medical need in Staphylococcus aureus bacteremia, therefore, the first approval of a therapy for this indication in over 15 years is highly welcome,” said Thomas Holland, MD, an associate professor in the Department of Medicine at the Duke University School of Medicine and chair of the data review committee of the ERADICATE study.

Another randomized, controlled, double-blind, multinational TARGET trial looked at ceftobiprole for ABSSSI. Researchers randomly assigned 679 patients to receive either ceftobiprole medocaril (335 subjects) or vancomycin plus aztreonam (344 subjects). The primary measure of efficacy was early clinical response 48 to 72 hours after start of treatment. Early clinical response required a reduction of the primary skin lesion by at least 20%, survival for at least 72 hours, and the absence of additional antibacterial treatment or unplanned surgery. Of the patients who received ceftobiprole, 91.3% achieved an early clinical response within the necessary period compared with 88.1% of those who received the comparator.

The efficacy in treating adult patients with CABP was evaluated in a randomized, controlled, double-blind, multinational, multicenter CABP trial. Researchers randomly assigned 638 adults hospitalized with CABP and requiring IV antibacterial treatment for at least three days to receive either ceftobiprole medocaril (314 subjects) or ceftriaxone with optional linezolid (the comparator; 324 subjects). The primary measure of efficacy was clinical cure rates at the test-of-cure visit, which occurred seven to 14 days after the end of treatment. Of the patients who received ceftobiprole, 76.4% achieved clinical cure compared with 79.3% of those who received the comparator. An additional analysis considered an earlier time of clinical success at day 3, which was 71% in patients receiving ceftobiprole and 71.1% in those receiving the comparator.

Given the similar course of CABP in adult and pediatric patients, today’s approval of ceftobiprole medocaril in children 3 months to 17 years old with CABP was supported by evidence from the CABP trial of ceftobiprole medocaril in adults and a trial in 138 children with pneumonia.

Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced generation cephalosporin antibiotic for IV administration, with rapid bactericidal activity against a range of gram-positive bacteria, such as S. aureus, including methicillin-resistant strains (MRSA), and gram-negative bacteria.

For adults with bacteremia, the most common side effects included anemia, nausea, hypokalemia, vomiting, diarrhea, increased levels of hepatic enzymes and bilirubin, increased blood creatinine, hypertension, leukopenia, fever, abdominal pain, fungal infection, headache and dyspnea.

For adults with ABSSSI, the most common side effects included nausea, diarrhea, headache, injection site reaction, increased levels of hepatic enzymes, rash, vomiting and dysgeusia.

For adults with CABP, the most common side effects included nausea, increased levels of hepatic enzymes, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, phlebitis, hypertension and dizziness. For pediatric patients with CABP, the most common side effects included vomiting, headache, increased levels of hepatic enzymes, diarrhea, infusion site reaction, phlebitis and fever.

Ceftobiprole medocaril comes with certain warnings and precautions, such as increased mortality in ventilator-associated bacterial pneumonia patients (an unapproved use), hypersensitivity reactions, seizures and other central nervous system reactions, and Clostridioides difficile infection.

“The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Zevtera will provide an additional treatment option for a number of serious bacterial infections,” said Peter Kim, MD, MS, the director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research. “The FDA will continue our important work in this area as part of our efforts to protect the public health.”

Zevtera was granted Priority Review, Fast Track and Qualified Infectious Disease Product designations for all three indications.