PDR Drug Update - June 2024

Novel Antibiotic Approved to Treat Trio of Complex Bacterial Infections

Effective and safe antibiotics are vital for the treatment of life-threatening resistant infections. The FDA supports efforts to increase the availability of drugs that match this growing need. The agency recently approved a new injectable antibiotic prodrug for three unique uses. The drug is an advanced cephalosporin called Zevtera (ceftobiprole medocaril sodium for injection), for intravenous use. The FDA approval includes indications for the treatment of adults with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis caused by methicillin-susceptible and methicillin-resistant isolates; adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the gram-positive and gram-negative microorganisms S. aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, and Klebsiella pneumoniae; and adults and patients aged 3 months to less than 18 years with community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the gram-positive and gram-negative microorganisms S. aureus (methicillin-susceptible isolates), Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Escherichia coli, and K. pneumoniae. Zevtera received Priority Review, Fast Track, and Qualified Infectious Disease Product designations for its SAB, ABSSSI, and CABP indications.

The National Institutes of Health describes ceftobiprole as an antibacterial that “binds to and inactivates penicillin-binding proteins, enzymes involved in the terminal stages of bacterial cell wall assembly and cell wall reshaping during bacterial growth and division.” As a cephalosporin, its ability to kill certain resistant bacteria or prevent them from continuing to grow makes this newly approved drug desirable as an option for helping overcome persistent infection. If patients have a history of hypersensitivity to ceftobiprole, Zevtera ingredients, or other cephalosporins, they should not take the medication. Warnings noted for Zevtera include hypersensitivity reactions, seizures and other CNS reactions, Clostridioides difficile–associated diarrhea, and increased mortality in patients with ventilator-associated bacterial pneumonia, which is an off-label use for the drug. Adverse effects associated with Zevtera differ depending on the reason for use, with some of the most prevalent being nausea, vomiting, and diarrhea.

Of note, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) are included in the safety data, but the safety and effectiveness of Zevtera for the treatment of HABP/VABP have not been established, and Zevtera is not approved for HABP or VABP. Approval for Zevtera was based on the concluding results from four controlled comparative phase 3 clinical trials:

Ceftobiprole in the treatment of patients with SAB - 191 patients received Zevtera 667mg, and 198 patients were treated with a comparator (daptomycin with optional aztreonam)
Ceftobiprole in the treatment of patients with ABSSSI - 334 patients received Zevtera 667mg, and 342 patients were treated with vancomycin plus aztreonam
Ceftobiprole in the treatment of patients with CABP - 310 patients received Zevtera 667mg, and 322 patients were treated with ceftriaxone 2g with or without linezolid 600mg
Ceftobiprole in the treatment of pediatric patients with pneumonia - 94 patients received Zevtera 13.3mg/kg to 26.7mg/kg, and 44 patients received either ceftriaxone 50-80mg/kg for CABP or ceftazidime 50mg/kg for HABP, with or without vancomycin 10-15mg/kg

Overall, the trials determined the successful efficacy of the drug and confirmed its potential for broad application for combating complex bacterial infection in various populations.

A new approval for an alternative antibiotic such as Zevtera is significant. Finding new ways to prevent and treat resistant infections remains a key healthcare strategy. According to the CDC’s report, Antibiotic Resistance Threats in the United States, 2019, improved antibiotic use is imperative, as the number of individuals facing antibiotic resistance reaches approximately 3 million in the US each year. Consequently, the label for Zevtera notes in its usage section that to reduce the development of drug-resistant bacteria and maintain effectiveness, Zevtera and other antibacterial drugs should be used only to treat or prevent infections that are proven, or strongly suspected, to be caused by susceptible bacteria. Stay informed about additional medication advances for hard-to-treat infections by exploring PDR by ConnectiveRx. You can also stay current by using the official PDR app, mobilePDR, which is available for free from your preferred app store.

FDA New Approvals

Beqvez

The FDA has approved Beqvez (fidanacogene elaparvovec-dzkt) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var capsid as detected by an FDA-approved test. Learn more about Beqvez

Hercessi

The FDA has approved Hercessi (trastuzumab-strf), a biosimilar to Herceptin (trastuzumab), to treat HER2-overexpressing breast and gastric or gastroesophageal junction adenocarcinoma. Learn more about Hercessi

Imdelltra

The FDA has approved Imdelltra (tarlatamab-dlle) for the treatment of adult patients with extensive-stage small cell lung cancer with disease progression on or after platinum-based chemotherapy. Learn more about Imdelltra

Ojemda

The FDA has approved Ojemda (tovorafenib), a type II RAF inhibitor, for the treatment of patients aged 6 months and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. Learn more about Ojemda

Opuviz

The FDA has approved Opuviz (aflibercept-yszy) as a biosimilar to Eylea (aflibercept). Opuviz is a vascular endothelial growth factor inhibitor indicated for the treatment of neovascular age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy. Learn more about Opuviz

Pivya

The FDA has approved Pivya (pivmecillinam) tablets for the treatment of female adults with uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. Learn more about Pivya

Xolremdi

The FDA has approved Xolremdi (mavorixafor) capsules for use in patients aged 12 years age and older with WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes. Learn more about Xolremdi

Yesafili

The FDA has approved Yesafili (aflibercept-jbvf), an interchangeable biosimilar to Eylea (aflibercept). Yesafili is intended for the treatment of neovascular age-related macular degeneration, visual impairment due to macular edema secondary to retinal vein occlusion, visual impairment due to diabetic macular edema, and visual impairment due to myopic choroidal neovascularization. Learn more about Yesafili

FDA New Formulations

Cyltezo

The FDA has approved the high-concentration, citrate-free formulation of Cyltezo (adalimumab-adbm) to treat multiple chronic inflammatory diseases. Learn more about Cyltezo

Ingrezza Sprinkle

The FDA has approved Ingrezza Sprinkle (valbenazine) capsules, a new oral granules formulation of Ingrezza (valbenazine) capsules prescribed for the treatment of adults with tardive dyskinesia and chorea associated with Huntington's disease. Learn more about Ingrezza Sprinkle

FDA New Indications

Breyanzi

The FDA has approved Breyanzi (lisocabtagene maraleucel), a CD19-directed chimeric antigen receptor T cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received two or more prior lines of systemic therapy. Learn more about Breyanzi

Libervant

The FDA has approved Libervant (diazepam) buccal film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients aged between 2 to 5 years with epilepsy. Learn more about Libervant

Tivdak

The FDA has approved the supplemental Biologics License Application granting full approval for Tivdak (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Learn more about Tivdak

FDA Alerts

Glatiramer Acetate Injection Products

The FDA is alerting patients, caregivers, and healthcare professionals of labeling updates for glatiramer acetate injection products. Updated labeling includes a new warning that using an autoinjector that is not compatible with a specific glatiramer acetate injection product may increase the risk for medication errors, such as a missed dose or administration of a partial dose. The FDA is also alerting patients and healthcare professionals that some glatiramer acetate injection products may be administered using an optional compatible autoinjector, while other glatiramer acetate injection products must only be injected using the prefilled syringe. Learn more about glatiramer acetate injection products

Thiopurines

The FDA is alerting healthcare professionals of the rare risk of intrahepatic cholestasis of pregnancy associated with the use of thiopurines (azathioprine, 6-mercaptopurine, and 6-thioguanine). Learn more about thiopurines

June 2024