Medical Countermeasures for Anthrax
Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis, which can cause human disease via gastrointestinal, cutaneous, or inhalational (pulmonary) routes. Although clinical manifestations of the disease differ by route, inhalational anthrax is the most lethal. The threat from a potential antibiotic-resistant strain of B. anthracis is also recognized. On January 20, 2004, the Secretary of Homeland Security determined that anthrax is a material threat to the U.S. population sufficient to affect national security.
HHS Medical Countermeasure Efforts
The U.S. Department of Health and Human Services (HHS) is pursuing a comprehensive strategy to address the threat of anthrax, and has made a substantial investment in the acquisition of medical countermeasures for the Strategic National Stockpile (SNS). This comprehensive approach includes acquisition of vaccines, antibiotics, and therapeutics to meet immediate public health needs in the event of an attack.
Under the Project BioShield Act (2004), Pandemic and All-Hazards Preparedness Act (2006), and Pandemic and All-Hazards Reauthorization Act (2013), BARDA’s strategy to support advanced development of critical medical countermeasures targets biothreats that have been determined by the Department of Homeland Security as Material Threats. An integral part of BARDA’s anthrax medical countermeasures (MCM) portfolio, the Anthrax Vaccines Program supports the PHEMCE strategy of having a compliment of antibiotics, vaccines and antitoxins that enable the U.S. Government to respond appropriately to an anthrax attack. When used in combination with antibiotics, anthrax vaccines can be administered in a post-exposure setting to those individuals at high risk or suspected exposure. The Anthrax Vaccines Program’s goal is one part of BARDA’s over-arching strategy to support advanced development of vaccines and antibiotics for post-exposure prophylaxis and anthrax antitoxins for the treatment of individuals who are symptomatic with anthrax disease. Specific goals of the anthrax vaccine program are to improve the utility of the currently-licensed anthrax vaccine (BioThrax®), to enhance the currently-licensed vaccine’s capability through development of an adjuvanted formulation, and to support the development of next-generation anthrax vaccine candidates that may further improve U.S. Government response capabilities against anthrax.
BARDA’s near-term strategy for anthrax vaccines leverages funding to support improvements in the utility and capability of BioThrax®. Significant progress toward this goal includes delivery of BioThrax® to the Strategic National Stockpile (SNS) under PBS funding and submission in late 2014 of the Supplemental Biologics License Application (sBLA) for post-exposure prophylaxis (PEP) indication, with anticipated FDA licensure in 2015. Projects are ongoing to expand the vaccine’s label indication for post-exposure prophylaxis, increase the current U.S. manufacturing production capacity and support the development of an enhanced vaccine formulation candidate with adjuvant (NuThrax®) that may produce a more rapid immune response with fewer doses required for protection. NuThrax® will enter Phase 3 clinical development in 2015 and potentially transition to procurement under PBS later in the decade. Successful execution of this near-term strategy may have a significant impact on U.S. preparedness against an anthrax attack and provide a substantial reduction in costs across the PHEMCE.
BARDA’s long-term anthrax vaccine strategy supports the advanced development of next-generation anthrax vaccine candidates that may further reduce the number of doses required for protection, improve response concept of operations with a thermostable vaccine in the field, and lower overall costs of stockpiling vaccine with longer shelf life and easier cold storage. Since 2006, BARDA has supported the advanced development of five (5) next-generation vaccine candidates, including recombinant protective antigen (rPA) and adenovirus-vectored vaccines. Three (3) next-generation candidates remain in the anthrax portfolio and soon will be evaluated in clinical trials for safety and immunogenicity to determine their potential as long-term replacement vaccines for the SNS. BARDA will manage its long-term anthrax vaccine development portfolio proactively through data-driven down selection of candidate vaccines that do not represent a transformative improvement in preparedness over existing stockpiled vaccine(s). This strategy will ensure wise use of limited resources and optimize the Nation's capability for responding to an anthrax attack. BARDA continues to coordinate with its PHEMCE partners to develop and procure robust and complementary medical countermeasure armamentaria necessary to respond to an anthrax event, including vaccines, therapeutics and antibiotics for the general and special populations.
Under the Project BioShield Act (2004), Pandemic and All-Hazards Preparedness Act (2006), and Pandemic and All-Hazards Reauthorization Act (2013), BARDA’s strategy to support advanced development of critical medical countermeasures targets biothreats that have been determined by the Department of Homeland Security as Material Threats. The material threat determination for Anthrax was issued in 2005. BARDA supports the Public Health Emergency Countermeasure Enterprise (PHEMCE) strategy of having vaccines and antibiotics for post-exposure prophylaxis and anthrax antitoxins in combination with antibiotics for the treatment of individuals who are symptomatic with inhalational anthrax disease. These anthrax antitoxin products were developed to address a gap in preparedness observed during the Amerithrax Attacks in 2001, when 50 percent of individuals with anthrax disease died despite treatment with antibiotics. A robust stockpile of complimentary antibiotics, vaccines and antitoxins was developed to prepare the U.S. government to appropriately respond to an anthrax attack in the event that antibiotics are unavailable or obsolete.
BARDA has supported the advanced development of six (6) antitoxin product candidates, both monoclonal and polyclonal. This support led to two (2) products being FDA-approved and procured under Project BioShield (PBS), making this the most advanced portfolio of candidates supported by BARDA’s Chemical, Biological, Radiological and Nuclear (CBRN) Division. Raxibacumab®, a monoclonal candidate manufactured by GlaxoSmithKline (GSK), was the first novel product to be approved (2012) under the FDA’s Animal Rule and the first product supported under PBS to achieve that milestone. A polyclonal product manufactured by Emergent/Cangene (anthrax immunoglobulin AIG, Anthrasil®) was licensed by the FDA in 2015, becoming the second anthrax antitoxin candidate and the third product supported under PBS to achieve licensure. Under PBS, BARDA funded the advanced development of both products toward FDA approval. BARDA has purchased, delivered and maintained these anthrax antitoxins in the Strategic National Stockpile (SNS) to treat symptomatic individuals in the event of an anthrax incident. BARDA also has provided PBS funds to collect additional human plasma to be manufactured into Anthrasil® final product in the future, as product currently in the SNS expires.
A third candidate, ETI-204 or Anthim (developed by Elusys) represents a second monoclonal in the BARDA Anthrax portfolio. Anthim was FDA approved in March 2016. With submission of the BLA, the project will soon transition to potential procurement under PBS. Inclusion of this candidate in the SNS will provide a second monoclonal product and a total of three (3) anthrax antitoxin products to address the need for treatment of symptomatic individuals. The ETI-204 candidate highlights the PHEMCE model of transitioning programs from early research and development at NIH to BARDA for advanced development and potential procurement under PBS, followed by maintenance by the SNS. The accomplishments of the Anthrax Antitoxins program have increased our preparedness to treat individuals with inhalational anthrax disease. Future goals for this program include transitioning from late stage development and procurement to sustaining preparedness levels and supporting Phase 4 post-marketing commitments and requirements under FDA licensure.