obiltoxaximab
Sources réglementaires consultées
Indications approuvées
- Traitement du charbon d’inhalation avec des antibactériens et prophylaxie lorsqu’aucune alternative appropriée n’est disponible. L’efficacité repose sur des études animales.
Mises en garde cliniques
- Peut provoquer une anaphylaxie et des réactions sévères à la perfusion ; la prophylaxie ne se justifie que si le bénéfice dépasse ce risque. Prémédiquer, surveiller et arrêter immédiatement en cas de réaction grave. — DailyMed, set_id 39ad8799-00a4-4fc8-9852-c0536350c474
- Mise en garde majeure · Ne prévient ni ne traite la méningite charbonneuse. — DailyMed, set_id 39ad8799-00a4-4fc8-9852-c0536350c474
Effets indésirables
Communs (≥1%)
Céphalées, prurit, infection respiratoire haute, toux, hématome de ponction veineuse, œdème ou douleur au site de perfusion, congestion nasale, urticaire et douleur des extrémités
Grossesse et allaitement
N’utiliser pendant la grossesse que si le bénéfice justifie le risque. Décider de l’allaitement après évaluation du bénéfice et du risque.
Bibliographie récente (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.
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.
Chemical, biological, radiological and nuclear (CBRN) agents can pose a significant risk to public health. Concerningly, for many of the CBRN threats there are no treatment options available. Conducting pivotal randomized controlled trials (RCTs) usually required for regulatory approval of medicinal products may not be feasible for medical countermeasures (MCM) intended for the treatment of CBRN threats because of the low prevalence and case numbers and ethical concerns on conducting RCTs, considering the potential serious health outcomes associated with CBRN threats. This is concerning, as it hampers the development and availability of new treatments against CBRN threats, which are needed for preparedness to ensure appropriate response to an outbreak. This review outlines alternative, regulatory flexible approaches that were used for the approval under exceptional circumstances of therapeutic MCMs against biological threats in the European Union. Considerations on the requirements of using animal efficacy data as key evidence for inferring efficacy from animals to humans, on using animal pharmacokinetic/pharmacodynamic data including pharmacometric modelling and simulation approaches to predict the human dose and on generating safety data in healthy humans are discussed. Challenges and advantages of this approach are highlighted, including the lessons learned based on the examples of tecovirimat, zanamivir and obiltoxaximab. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.