Abthrax (raxibacumab) / Emergent Biosolutions - LARVOL DELTA

United States' regulatory approved pharmacotherapies for nuclear reactor explosions and anthrax-associated bioterrorism. (PubMed, Expert Opin Drug Saf) - "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)...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."

Journal • Review • Infectious Disease • Oncology • Respiratory Diseases

Pre- and Postlicensure Animal Efficacy Studies Comparing Anthrax Antitoxins. (PubMed, Clin Infect Dis) - "These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment."

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Pre- and Postlicensure Animal Efficacy Studies Comparing Anthrax Antitoxins. (PubMed, Clin Infect Dis) - "These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment."

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Survival of Patient With Hemorrhagic Meningitis Associated With Inhalation Anthrax. (PubMed, Clin Infect Dis) - "His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Respiratory Diseases • Septic Shock

A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis. (PubMed, Front Microbiol) - "Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium."

Journal • Preclinical • Immune Modulation • Infectious Disease • Inflammation

Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives. (PubMed, ACS Infect Dis) - "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."

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Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea? (PubMed, Front Med (Lausanne)) - "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...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."

Journal • Review • Immunology • Infectious Disease • Malaria • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Transplant Rejection • Transplantation

Population pharmacokinetics of raxibacumab in healthy adult subjects. (PubMed, Br J Clin Pharmacol) - "A dose of 40 mg/kg provided comparable exposure across the overall healthy subject population. IIV in raxibacumab versus time profiles could partially be accounted for by differences in body weight."

Clinical • Journal • PK/PD data

Extrapolation and dosing recommendations for raxibacumab in children from birth to < 18 years of age. (PubMed, Br J Clin Pharmacol) - "Age-related maturation processes may affect raxibacumab clearance in young patients. The proposed dosing regimens take into account effects of body weight and maturation processes on the elimination of raxibacumab."

Clinical • Journal • Pediatrics

A Review of the Efficacy of FDA-Approved B. anthracis Anti-Toxin Agents When Combined with Antibiotic or Hemodynamic Support in Infection- or Toxin-Challenged Preclinical Models. (PubMed, Toxins (Basel)) - "At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Administration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. To provide a broader view of the potential effectiveness of these agents, this review examines the controlled preclinical experience either in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines. The strength and weaknesses of these preclinical experiences are discussed."

FDA event • Journal • Review • Septic Shock

Effect of raxibacumab on immunogenicity of Anthrax Vaccine Adsorbed: a phase 4, open-label, parallel-group, randomised non-inferiority study. (PubMed, Lancet Infect Dis) - P4 | "Co-administration of raxibacumab with AVA does not negatively affect AVA immunogenicity. This finding suggests that combining raxibacumab with AVA might provide added benefit in postexposure prophylaxis against inhalational anthrax."

Clinical • Head-to-Head • Journal • P4 data

Effect of Raxibacumab on Immunogenicity of Anthrax Vaccine Adsorbed (clinicaltrials.gov) - P4; N=30; Active, not recruiting; Sponsor: GlaxoSmithKline; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Immunology

Approval of Raxibacumab for the Treatment of Inhalation Anthrax Under the US Food and Drug Administration "Animal Rule". (PubMed) - Front Microbiol - "Raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or not appropriate. The developmental process required for approval of Raxibacumab illustrates many of the challenges that product developers may encounter when pursuing approval under the Animal Rule and highlights a number of important regulatory and policy issues."

Journal • Biosimilar

Clinical Benefit, Safety and PK of Raxibacumab in Subjects Exposed to Bacillus Anthracis (clinicaltrials.gov) - P4; N=100; Not yet recruiting; Sponsor: Emergent BioSolutions; Trial completion date: Apr 2021 ➔ Jul 2025; Trial primary completion date: Apr 2021 ➔ Jul 2025

Trial completion date • Trial primary completion date • Biosimilar

Monoclonal antibodies against infectious microbes: so long and too little! (PubMed, Infect Disord Drug Targets) - "So far, only five mAbs have been approved for the management of infectious states - since, the marketing authorization (1998) given to palivizumab (Synagis®) for the prophylaxis of lower respiratory tract disease caused by respiratory syncytial virus in pediatric patients. Ibalizumab-uiyk (Trogarzo™) used for the management of multidrug resistant HIV-1 infection not yielding to at least 10 antiretroviral drugs previously was approved recently. Among the three antibacterial mAbs, raxibacumab (ABthrax®/ Anthrin®) and obiltoxaximab (Anthim®) are indicated for the treatment and prophylaxis of inhalation anthrax due to Bacillus anthracis; bezlotoxumab (Zinplava®) is used to reduce the recurrence of Clostridium difficile infection...The current cutting-edge engineering technologies revolutionizing the production of mAbs include phage-displayed antibody libraries, cloning from single-memory B cells or single-antibody-secreting plasma B cells,..."

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