Mlm Reviews
Raxibacumab (ABthrax, HGS ) Review
Monoclonal antibody protection from Inhalation Anthrax toxin ( bioterror)A multimedia review of the first monoclonal antibody (mAbs) to protect from inhalation Anthrax toxin is presented. Since it is unethical to do human studies with anthrax, animal studies in 2 species along with pharmacokinetics studies in healthy volunteers are sufficient for FDA approval ( Animal rule 2002). The NDA/BLA was filed in May 2009 and the FDA Antiinfective Drug Advisory Committee reviewed the safety and efficacy data on October 2009 and recommended its approval. FDA and EMA have granted fast track and orphan drug status to Raxibacumab. FDA inspection and audit of the clinical trial site revealed important concerns about the reliability, quality and validity of the human pharmacokinetics data. It is assumed that HGS has responded to the FDA audit and taken steps to rectify the error. The regulatory clock has probably restarted once the quality issues raised by the FDA were addressed and approval is expected soon. HGS has supplied the drug to the CDC national stockpile in 2009 (worth $ 180 million) and has contract to supply more up to 2012.
This site complies with the HONcode standard for trustworthy health information: verify here.
Search only trustworthy HONcode health websites.
Publishers, corporations, educational, academic, government, foundations, organizations and readers are invited to read the following document for funding, sponsorship and commercial license opportunities. The document explains author's policy: to provide trustworthy information, conflict of interest, marketplace and privacy and data protection issues.
Sponsorship, Commercial Use and IPR The article discusses many unapproved, unlabeled and unevaluated uses/indications of products under clinical investigation which have not been approved or reviewed by the FDA/EMA. Raxibacumab has not been reviewed or approved by the FDA/EMA.
 QR-Code of this knol: http://goo.gl/nF5dM.qr and short URL http://goo.gl/nF5dM. Use the QR-Code for your cell phones and mobile devices (Handy, GSM, Bluetooth, BlackBerry...) be prepared for 21th Century ;-) |
Introduction
Two recent outbreaks of Anthrax were probably both linked to accidental or deliberate release of the bacteria Bacillus anthracis from Bio Weapon laboratories in the USSR and USA. An accident in the germ warfare lab in the former Soviet Union killed 68 persons in Sverdlovask (Yaketerinburg). At least 77 exposed persons survived exposure to Anthrax aerosol and were vaccinated and treated with antibiotics. [1]
Bacillus anthracis spores in the powder form were mailed in 2001 through the US postal service resulting in exposure of 22 persons, 11 each with cutaneous and inhalation anthrax. Five inhalation anthrax patients died despite antibiotics treatment and only 6 persons survived . All patients with cutaneous anthrax responded to antibiotics and survived. This comes to a high mortality rate of 45%.[2][3] Current antibiotics treatment is aimed at eradicating B. anthracis bacteria. Antibiotics fail to protect against bacterial toxins released in the host. The bacteria releases 2 toxins Lethal Toxin LT and Edema Toxin ET. These toxins are formed through bacterial proteins Protective Antigen PA, Lethal Factor LT and Edema Factor EF.
The US Defence efforts to deal with bioterror are described in a recent article. [4]
Images
Under Creative Commons Attribution 3.0 License Image 1: CDC PHIL 4550
Emerging Infectious Diseases (EID) cover artwork for Volume 8, Number 10, October 2002 issue.
The cover artwork titled, "Postman Reading Mail" was a Saturday Evening Post cover, February 18, 1922, and was created by Norman Rockwell, (1894-1978). The art was provided as a courtesy of the Curtis Publishing Company, Indianapolis, Indiana, USA.
![[BIOHAZARD LOGO]](http://www.freelabs.com/~whitis/biosafety/logo-biohazard.gif){kind=logo}
Anthrax & Bioterror
Bacillus anthracis is considered a potential agent for bioterrorism as its spores can be weaponized in the aerosol or powder form. The gram positive toxin producing B. anthracis can cause cutaneous, gastrointestinal and inhalation anthrax depending on the route of exposure. Inhalation anthrax is the most deadly form of exposure. FDA approved several existing antibiotics under Emergency fast track approval based on efficacy in animal models. Ciprofloxacin, doxycycline and peniccillin G were fast tracked approved by the FDA in 2000-2001 for inhalation anthrax based on efficacy data in Monkeys. Levofloxacin was approved in 2004 under similar rules and has emerged as the first choice antibiotic for anthrax exposure. [5][6][7]November 16-17, 2010: Vaccines and Related Biological Products Advisory Committee Briefing Document Pathway to Licensure for Protective Antigen-based Anthrax Vaccines for a Post-exposure Prophylaxis Indication Using the Animal Rule (PDF - 655KB)
Images and Videos
YouTube Video
Under Creative Commons Attribution 3.0 LicenseCDC PHIL ID 10123
CDC PHIL 11748
This image depicted numbers of Bacillus anthracis bacterial colonies, which had been allowed to grow on sheep's blood agar (SBA) for a 24 hour period. Note the classical appearance exhibited in the colonial morphology including a ground-glass, non-pigmented texture with accompanying "comma" projections from some of the individual rough-edged colonies.
YouTube Video
Under Creative Commons Attribution 3.0 License
 |
| PicApp Images Permitted Use |
A bicyclist rides past the American Media Inc. building while wearing a respirator October 10, 2001 in Boca Raton, FL. FBI agents continue to investigate the newspaper offices where two men were exposed to Anthrax. These incidents prompted heightened fear of bioterrorism across the country during 2001. (Photo By Eliot J. Schechter/Getty Images) Content 2010 Getty Images All rights reserved.
 |
| PicApp Images Permitted Use |
Content 2010 Getty Images All rights reserved.
Anthrax Vaccine
Live attenuated anthrax vaccine was one of the earliest vaccine produced by Louis Pasteur in late 19th century. NIH in 1970 approved Anthrax Vaccine Absorbed (aluminium hydroxide as adjuvent) from Emergent BioSolution (BioThrax AVA and BioThrax IM) which was later on certified/approved by the FDA.[5][6][8][9] US military persons have the mandatory requirement to get vaccinated. The dose schedule is 0, 1, 6, 12 and 18 months followed by annual boosters. Extensive monitoring by CDC and a review by Institute of Medicine found the vaccine to be safe. Department of Health and Human Services has awarded R&D contracts to biotechnology firms to come with alternative vaccines limited to a 3 dose schedule. Initial contract awarded to Vaxgen was cancelled as the company failed to meet deadlines and agreed milestones. Pharm Athen has won a contract for over $ 213 million to develop Spar Vax anthrax vaccine.[10] . It has a follow up 3rd generation anthrax vaccine in development.
Monoclonal Antibody mAbs
HGSI discovered that a monoclonal antibody targeting the PA bacterial protein was able to protect against bacterial anthrax toxin. The R&D funding was provided by HHS and FDA Animal Rule of 2002 provided for fast track and orphan approval after animal protection studies in 2 species. In addition to HGSI, two other mAbs from Elusys (Anthim) and Pharm Athen and BMS Medarex (Valortim) anti PA mAbs are in development.[8][11]
All anthrax mAbs were designated fast track and orphan drug status by the FDA and received HHS funding through NIH, BARDA or CDC. Under Creative Commons Attribution 3.0 License
 |
| Image from Pharm Athen |
Valortima fully human mAbs was licensed by Medarex/BMS to Pharm Athen and received $ 24 million of government funding. Valortim binds to a new site of the Anthrax protective antigen. Preclinical and clinical Phase I studies were completed. In animal models, valortim protected 100% of animals from exposure to lethal spores of Anthrax, was effective at all doses tested and even in post exposure settings.[14]. Valortim advantage was that the mAbs was effective both in prophylaxis and therapy post infection and neutralizes both the cell bound and free circulating anthrax toxin.
Decade after anthrax attacks, worry over stockpile
Mon 6:26 pm ET (AP)
Anthrax vaccine -- check. Antibiotics -- check. A botulism treatment -- check. Smallpox vaccine -- check. Ten years after the anthrax attacks brought home the reality of bioterrorism, the nation has a stockpile of some basic tools to fight back against a few of the threats that worry defense experts the most.
Raxibacumab
It is an anti PA human recombinant IgG1 mAb and prevents formation of anthrax toxins.The mab was selected based on its ability to neutralize PA in cell line assays. it inhibited lethal toxin mediated cell death. Raxibacumab for clinical studies was produced by murine cell lines and underwent 6 purification and filteration steps.
Nomenclature| Prefix | Sub stem A | Sub stem B | Suffix common |
| Raxi | ba/bac | u | mab |
| Innovator choice | bacterial | human | monoclonal antibody |
Raxibacumab is a human monoclonal antibody for bacterial infections.
Animal studies in both pre and post exposure were done to determine the dose, efficacy, therapeutic efficiency and duration of efficacy. these studies were done in rats, rabbits and monkeys model of inhalation anthrax. The mAb provided protection and increased survival in all the animal models and was safe. The mAb increased survival rate and time and decreased signs of anthrax disease and did not interfere with antibiotics. survival rate in animal studies was upto 100% in monkey and 95% in rabits. Studies in monkeys and rabbits showed that the mAbs provided no additional benefit when added to the conventional antibacterial regimen. The recommended dose for human use is 40 mg/kg iv over 2 hrs 15 minutes with diphenhydramine pretreatment.[15][16]
Raxibacumab was tested in 4 Phase I clinical pharmacology and safety studies. Three studies were done with iv dosing and over 400 sunjects were treated. over 326 subjects received 40 mg/kg dose many in single anmd repeat doses. Comparable levels as predicted from animal studies were observed in human PK studies. The FDA advisory committee has recommended approval by a vote of 16 to 7 (against).[17][18] [19][20]
Under Creative Commons Attribution 3.0 License Protects against Anthrax induced cell death.
Rabbit Model of inhalation Anthrax
Images and data from HGSI.
Live MED and R&D RSS Feeds
Raxibacumab Google News (U.S.)Raxibaclumab Google News (U.S.)
Bioterror & Anthrax Market
The market is dependent on government orders which can be sudden and on an urgent basis. Departments of Defence and Health and Human Services are the major clients along with NATO, ECDC and European governments. National stockpiles and annual renewal are the only market and advance purchase order or commitment before production of the drug is required. The US has over 2 billion dollar worth of antibiotics and vaccines to deal with anthrax emergency in the national strategic stockpile after the outbreak of Anthrax threats in 2001 and under Bioshield project. Europe might have similar levels of Stockpile. HGS has delivered 20, 000 doses of raxibacumab in 2009 and reported sales of $180 million. The company has orders for 45000 more doses to be delivered by 2012. The new contract is worth $150 million to HGS.
The current anthrax vaccine market based on 75 million doses for the US stockpile is over $ 1 billion. It may grow to 1.5 billion in future and the EU market may add $ 1 billion to make it $2.5 billion. Monoclonal antibodies market may total $ 1 billion as well.
Monoclonal Antibody Guide
Monoclonal Antibody Guide, KnolsMonoclonal Antibody Guide, Knols
Acknowledgements
Thanks are due to Mr. Jean-Antoine de Mandato (PDP, Geneva) for providing office facilities and administrative support.
Mark it as your favorite knol
Author's publications
Visit also : Knol-its possibilities, who explains you more about Knol...
Author's publications
Visit also : Knol-its possibilities, who explains you more about Knol...
Share and Communicate
Share |
Social Bookmarking Sponsorship, Commercial Use and IPR
sponsorship, commercial use and iprsponsorship, commercial use and ipr
TVI Express - An Expert MLM Review
Next page: Network Marketing Products
Recommended Products
Mlm Reviews News
MLM Network Marketing Your Biggest Problem Solved
10 Feb 2012 at 11:14pm MLM Network Marketing YOUR Biggest Problem Solved In “MLM Network Marketing” what is you biggest problem? Hint, it is not making money! It is making money fast enough to survive long enough to make a living. It does not matter …Read more...
Impressive MLM Advertising System Generating an Online Buzz - MLM Profit ... ...
1 Feb 2012 at 10:50am SBWire (press release) An impressive MLM advertising system is already creating a wave of enjoyment in the online advertising neighborhood. New York, NY -- (SBWIRE) -- 02/01/2012 -- MLM Profit Marketing System happens to be an ingenious MLM Advertising and marketing system ... |
Read more...
