raxibacumab
Regulatory sources consulted
Approved indications
- Treatment of inhalational anthrax with antibacterial drugs and prophylaxis when appropriate alternatives are unavailable. Efficacy is based on animal studies.
Clinical warnings
- It may cause anaphylaxis and severe infusion reactions; administer where immediate treatment is available and stop the infusion for a severe reaction. — DailyMed, set_id f6927e91-bb46-47b3-ab66-f9d8a9d7b12a
- Major warning · It does not cross the blood-brain barrier and does not prevent or treat anthrax meningitis. — DailyMed, set_id f6927e91-bb46-47b3-ab66-f9d8a9d7b12a
Adverse events
Common (≥1%)
Rash, pain in extremity, pruritus, somnolence, headache, and injection-site reaction, erythema, or pain
Pregnancy and lactation
Use during pregnancy only when expected benefit justifies risk. Decide on breastfeeding after assessing benefit and risk.
Recent literature (PubMed)
The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of the invading pathogen by the immune system is promoted. As compared to antibiotics, the pathogen-selective antivirulence drugs hold promise to minimize collateral damage to the beneficial microbiome. Also, selective pressure for resistance is expected to be lower because bacterial viability is not directly affected. Antivirulence drugs are being developed for stand-alone prophylactic and therapeutic treatments but also for combinatorial use with antibiotics. This Review focuses on drug modalities that target bacterial exotoxins after the secretion or release-upon-lysis. Exotoxins have a significant and sometimes the primary role as the disease-causing virulence factor, and thereby they are attractive targets for drug development. We describe the key pre-clinical and clinical trial data that have led to the approval of currently used exotoxin-targeted drugs, namely the monoclonal antibodies bezlotoxumab (toxin B/TcdB, Clostridioides difficile), raxibacumab (anthrax toxin, Bacillus anthracis), and obiltoxaximab (anthrax toxin, Bacillus anthracis), but also to challenges with some of the promising leads. We also highlight the recent developments in pre-clinical research sector to develop exotoxin-targeted drug modalities, i.e., monoclonal antibodies, antibody fragments, antibody mimetics, receptor analogs, neutralizing scaffolds, dominant-negative mutants, and small molecules. We describe how these exotoxin-targeted drug modalities work with high-resolution structural knowledge and highlight their advantages and disadvantages as antibiotic alternatives.
Raxibacumab is a fully humanized monoclonal antibody that blocks the interaction of Bacillus anthracis toxins, thereby protecting target cells from its effects. Raxibacumab is approved in the USA for the treatment of adults and children with inhalational anthrax in combination with antibiotics, and for prophylaxis of inhalational anthrax. The aim of this investigation was to characterise the population pharmacokinetics and assess the effect of baseline demographic covariates on the disposition of raxibacumab. The data used for this analysis were obtained from 3 clinical trials and include 2229 blood samples from 322 healthy subjects who were randomised to receive a 40 mg/kg intravenous dose of raxibacumab over a period of 2.25 hours. Population pharmacokinetic modelling was performed using a nonlinear mixed effects approach. Secondary parameters of interest were the area under the curve, maximum concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28 days in any monkey challenged with B. anthracis that died. Raxibacumab exposure in healthy subjects was described by a 2-compartment model. Interindividual variability was estimated for all model parameters, whilst residual variability was described by a proportional and additive error model. Weight was the only influential covariate with significant effect on disposition parameters. A dose of 40 mg/kg provided comparable exposure across the overall healthy subject population. Interindividual variability in raxibacumab vs. time profiles could partially be accounted for by differences in body weight.
Nuclear reactor incidents and bioterrorism outbreaks are concerning public health disasters. Little is known about US Food and Drug Administration (FDA)-approved agents that can mitigate consequences of these events. We review FDA data supporting regulatory approvals of these agents. We reviewed pharmaceutical products approved to treat Hematopoietic Acute Radiation Syndrome (H-ARS) and to treat or prevent pulmonary infections following Bacillus anthracis (anthrax) exposure. Four drugs were approved for H-ARS: granulocyte-colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor, pegylated G-CSF, and romiplostim. For bioterrorism-associated anthrax, the FDA approved five antibiotics (doxycycline, penicillin-G, levofloxacin, moxifloxacin, and ciprofloxacin), two monoclonal antibodies (obiltoxaximab and raxibacumab), one polyclonal antitoxin (Anthrax Immune Globulin Intravenous) and two vaccines (Anthrax Vaccine Adsorbed and Anthrax Vaccine Adsorbed with an adjuvant). A national stockpile system ensures that communities have ready access to these agents. Our literature search was based on data included in drugs@FDA (2001-2023). Two potential mass public health disasters are aerosolized anthrax dissemination and radiological incidents. Five agents authorized for anthrax emergencies only have FDA approval for this indication, five antibiotics have FDA approvals as antibiotics for common infections and for bacillus anthrax, and four agents have regulatory approvals for supportive care for cancer and for radiological incidents.
Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.