Abstract
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The Ebola medical countermeasures (MCM)—drugs, vaccines, and diagnostics—being discussed and tested today have been developed with the significant investment in biodefense programs over the past decade. Ebola virus is a Category A priority pathogen, and it is judged to be one of a few biological agents that pose the “highest risk to national security and public health.” 2 Because Ebola has been identified as a Category A pathogen, the federal government has dedicated resources to developing medical countermeasures to be used in the event that Ebola is used against the US in a bioterrorism attack.
The US government has made sustained biodefense-related investments in basic and applied R&D aimed at producing anti-Ebola MCMs for more than a decade. 3 Investments made by the National Institute of Allergy and Infectious Diseases (NIAID), through Biodefense and Emerging Infectious Diseases Program funding, and by the Department of Defense (DoD) Defense Threat Reduction Agency (DTRA), through the Chemical and Biological Defense Program (CBDP), have led to the development of a majority of the countermeasures in the pipeline. 3 In addition, biodefense investments in building advanced development capabilities at the Biomedical Advanced Research and Development Authority (BARDA) and in building mechanisms for emergency clinical testing and emergency regulatory approval at the Food and Drug Administration (FDA) are now proving critical to current efforts to rapidly confirm safety and efficacy and ramp up production of countermeasures.
NIAID has been a major source of Ebola research and research support as part of the US biodefense enterprise. NIAID works to understand the pathophysiological processes that make Ebola and other Category A pathogens so worrisome to public health and national security agencies; it works to develop animal models that can be used to test the efficacy of countermeasures and develops treatment strategies for viral hemorrhagic fevers and other diseases. 4
Since fiscal year (FY) 2004, NIAID has invested over $333 million specifically focused on Ebola, including basic research on the virus and research toward development of vaccines, therapeutics, and diagnostics (Martin Johnson, Chief, Resource Planning and Mission Integration Branch, NIAID, NIH, personal communication, September 19, 2014) (see Table 1).
NIAID Support for Ebola Research FY2004-13 (in $Millions)
Note. Adapted from personal communication with NIAID. Funding amounts were provided by NIAID in September 2014. Amounts here exclude funding as part of the American Recovery and Reinvestment Act (ARRA).
DoD has also invested in medical countermeasures development for hemorrhagic fever viruses as part of their agency-wide Chemical and Biological Defense Program. According to a press release by DoD, DTRA has invested over $300 million since FY2003 in basic and applied research programs that work to develop vaccines, drugs, and diagnostics for Ebola and other diseases, although further breakdown of this funding was not provided by DTRA. 5 This research has been conducted with the primary purpose of protecting the warfighter, yet these investments are also proving to have benefits for civilian populations. Support provided by DTRA, the US Army Medical Research Institute of Infectious Diseases (USAMRIID), and the Defense Advanced Research Projects Agency (DARPA) for research on Ebola has contributed to a number of countermeasures that may be useful in the current crisis if they are ready and scaled up in time.
As a direct result of US biodefense investments since 2003, there are at least a dozen vaccines and therapeutics in the pipeline for Ebola (see Table 2). Many of these countermeasures are currently in phase 1 clinical trials, and for some phase 2 and 3 clinical trials have begun or are being planned for 2015. A number of the therapeutics under development have been provided to Ebola-infected patients in this outbreak under “compassionate use” regulations, which allow for use of promising but experimental drugs and vaccines for patients with life-threatening illnesses. 28 While conclusions cannot be drawn from the few patients who have received experimental treatments, it is noteworthy that drugs and vaccines were available to give in limited quantities.
Note. Adapted from a presentation by Dr. Peter Jahrling at the JHSPH Ebola Crisis Dean's Symposium on October 15, 2014. Information has been updated. 8
Current Funding Picture
Recently, NIH and DoD have continued to provide support for advancing research into many of the countermeasures included in Table 2. They have also provided support for clinical trials and have partnered with private sector pharmaceutical companies to expand production capacity of countermeasures for use in clinical trials. Some of the funding for these efforts has been derived from current MCM budgets, and other funding has been reprogrammed. In October 2014, Congress gave approval for reprogramming $750 million in DoD war funds to support Operation United Assistance, the deployment of military assets to assist the government of Liberia. As of December 1, 2014, $25.6 million of the $750 million in funding had been expended by DoD for Ebola countermeasures research and development. 29
Going forward, on December 16, 2014, the President signed into law the Consolidated and Further Continuing Appropriations Act, 2015, which appropriates a total of $5.4 billion in emergency funding to support the US response to Ebola. Of that total, approximately $1.1 billion will go to Ebola MCM research, development, procurement, and approval (see Table 3). 30
Note. Adapted from the text of H.R. 83, the Consolidated and Further Continuing Appropriations Act, 2015. 30
Future Investments Needed
The current Ebola crisis has shown that investments in biodefense and health security have benefits beyond enhancing our preparedness for bioterrorism and deserve increased and sustained support over the long run.