The FDA recently announced the approval of Zevtera (ceftobiprole medocaril sodium for injection) for three difficult-to-treat infectious conditions. The injectable antibiotic is approved for adults with Staphylococcus aureus bloodstream (SAB) infections (bacteremia), including those with right-sided infective endocarditis; adults with acute bacterial skin and skin structure infections (ABSSSI); and adult and pediatric patients aged 3 months to <18 years with community-acquired bacterial pneumonia (CABP).
Basilea Pharmaceutica International Ltd., based in Basel, Switzerland, was granted Priority Review, Fast Track, and Qualified Infectious Disease Product designations for the CABP, ABSSSI, and SAB indications.
“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.”
A randomized, controlled, double-blind, multinational, multicenter trial evaluated Zevtera’s efficacy in treating SAB. For the trial, the study team randomly assigned 390 subjects to receive either Zevtera or daptomycin plus optional aztreonam—the comparator. The primary measures of efficacy for the trial were survival, symptom improvement, S aureus bacteremia bloodstream clearance, no new S aureus bacteremia complications, and no use of other potentially effective antibiotics at the posttreatment evaluation visit; that visit occurred 70 days after being randomly assigned an antibiotic. Overall success was achieved in 69.8% of subjects who received Zevtera compared with 68.7% of subjects who received the comparator.
The antibiotic’s efficacy in treating ABSSSI was evaluated in a randomized, controlled, double-blind, multinational trial involving 679 participants who received either Zevtera or vancomycin plus aztreonam. With the primary measure of efficacy defined as early clinical response 48 to 72 hours after start of treatment, 91.3% of patients achieved an early clinical response within the necessary timeframe compared with 88.1% of subjects who received the comparator. Early response was measured by 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.
Zevtera’s efficacy in treating adult patients with CABP was evaluated in a randomized, controlled, double-blind, multinational, multicenter trial of 638 adults hospitalized with CABP and requiring IV antibacterial treatment for at least 3 days. The comparison was between Zevtera or ceftriaxone with optional linezolid, and 76.4% of those receiving the new drug achieved clinical cure compared with 79.3% of subjects who received the comparator. The measure was of clinical cure rates at test-of-cure visit, which occurred 7 to 14 days after end-of-treatment. An additional analysis considered an earlier timepoint of clinical success at Day 3, with 71% success in patients receiving Zevtera and 71.1% in patients receiving the comparator.
“Given the similar course of CABP in adults and pediatric patients, today’s approval of Zevtera in pediatric patients three months to less than 18 years with CABP was supported by evidence from the CABP trial of Zevtera in adults and a trial in 138 pediatric subjects [aged] 3 months to less than 18 years of age with pneumonia,” the FDA reported.
Side effects of Zevtera differed somewhat based on usage:
• For adults with SAB, the most common side effects of Zevtera included anemia, nausea, low levels of potassium in the blood (hypokalemia), vomiting, diarrhea, increased levels of certain liver tests (hepatic enzymes and bilirubin), increased blood creatinine, high blood pressure, low white blood cell count (leukopenia), fever, abdominal pain, fungal infection, headache, and shortness of breath (dyspnea)
• For adults with ABSSSI, the most common side effects of Zevtera included nausea, diarrhea, headache, injection site reaction, increased levels of hepatic enzymes, rash, vomiting, and altered taste (dysgeusia)
• For adults with CABP, the most common side effects of Zevtera included nausea, increased levels of hepatic enzymes, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, vein inflammation (phlebitis), high blood pressure, and dizziness
• For pediatric patients with CABP, the most common side effects of Zevtera included vomiting, headache, increased levels of hepatic enzymes, diarrhea, infusion site reaction, vein inflammation (phlebitis), and fever.
The FDA cautioned that patients should not use Zevtera if they have a known history of severe hypersensitivity to ceftobiprole or any of the components of the drug or other members of the cephalosporin antibacterial class.
Other warnings and precautions concern increased mortality in ventilator-associated bacterial pneumonia patients (an unapproved use), hypersensitivity reactions, seizures and other central nervous system reactions, and Clostridioides difficile-associated diarrhea.
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