FDA Approves Zevtera for Serious Bacterial Infections

The FDA has approved Basilea’s Zevtera (ceftobiprole medocaril sodium) to treat three different infections: adults with Staphylococcus aureus bloodstream infections, including those with right-sided infective endocarditis; adults with acute bacterial skin and skin structure infections; and adult and pediatric patients three months to less than 18 years old with community-acquired bacterial pneumonia.

"Complicated Staphylococcus aureus infections have a high mortality rate and are associated with substantial morbidity. We need more options for treating these infections, especially if MRSA is involved," Vance G. Fowler, Jr., M.D., professor in the Departments of Medicine and Molecular Genetics & Microbiology at the Duke University School of Medicine and academic lead investigator, said in a news release.

Zevtera is a beta-lactam antibiotic for intravenous administration. It has activity against Gram-positive bacteria including methicillin-resistant strains of Staphylococcus aureus (MRSA). Zevtera will launch later this year with an unnamed U.S. partner, a Basilea spokesperson said. The partner will be announced by the middle of the year. Zevtera's price has not yet been determined.

For the majority of the uses (i.e., in the hospital), Zevtera is expected to be covered as part of the diagnosis-related group (DRG) bundled payment system. The DRG is determined by the diagnosis.

The approval of Zevtera was based on three separate studies. In the Staphylococcus aureus bloodstream trial, researchers enrolled 390 patients who were treated either with Zevtera or daptomycin plus optional aztreonam. A total of 69.8% of patients who were treated with Zevtera achieved overall success compared with 68.7% who received daptomycin.

In this trial, the most common side effects included anemia, nausea, low levels of potassium in the blood, vomiting, diarrhea, increased levels of certain liver tests, increased blood creatinine, high blood pressure, low white blood cell count, fever, abdominal pain, fungal infection, headache and shortness of breath.

In the acute bacterial skin and skin structure infections trial, 679 adults received either Zevtera or vancomycin plus aztreonam. Of those who received Zevtera, 91.3% achieved an early clinical response compared with 88.1% of those in the vancomycin/aztreonam arm. Early clinical response, the primary end point, was defined as a response seen between 48 and 72 hours after start of treatment.

The most common side effects were nausea, diarrhea, headache, injection site reaction, increased levels of hepatic enzymes, rash, vomiting and altered taste

In the community-acquired bacterial pneumonia trial, 638 patients received either Zevtera or ceftriaxone with optional linezolid. Of those who received Zevtera, 76.4% achieved clinical cure compared with 79.3% owho received the comparator. The most common side effects of Zevtera included nausea, increased levels of hepatic enzymes, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, vein inflammation, high blood pressure and dizziness.

Basilea’s phase 3 program for ceftobiprole is funded in part with federal funds from the Department of Health and Human Services (HHS); the Administration for Strategic Preparedness and Response (ASPR); Biomedical Advanced Research and Development Authority (BARDA).