More than 10,000 people have died of Ebola virus disease (EVD) since the outbreak in West Africa began in December 2013. An epidemic of this magnitude, whether naturally occurring or caused by a biowarfare agent, could compromise both the U.S. health care system and the U.S. military’s ability to defend this country and its allies. This possibility, long recognized by the Department of Defense (DoD), drives the department’s development of medical countermeasures. The response to the current Ebola outbreak demonstrates how DoD prepares for a medical threat without knowing (1) where it will happen, (2) when it might happen, (3) what the disease will be, and (4) what local resources will be immediately available.
Ebola is a virus that has been classified by the Federal Select Agent Program as a Tier 1 Select Agent—one that presents the “greatest risk of deliberate misuse with the most significant potential for mass casualties or devastating effects.” Beginning in 2007, the Joint Project Manager for Medical Countermeasure Systems (JPM-MCS), a little-known office tucked inside DoD’s larger Chemical and Biological Defense Program, worked alongside civilian and military partners to develop detection, protection, and treatment capabilities against threats such as Ebola virus disease. All the products produced by JPM-MCS must be approved for use by the U.S. Food and Drug Administration (FDA).
Current Ebola Outbreak
In March 2014, a patient in Guinea presented with fever, severe diarrhea, hemorrhaging, and vomiting—frightening symptoms that can be caused by several diseases. While the doctors suspected one in particular—Ebola—they needed confirmation to begin proper treatments and institute containment procedures. Blood samples were taken for testing. The assay selected for testing, now considered the gold standard for Ebola detection tools, was developed by JPM MCS. Ebola was confirmed.
From the start of the outbreak, JPM-MCS was a key asset in the response. The team’s experience and expertise helped provide for EVD detection, protection, and treatment for both foreign nationals and U.S. citizens and military personnel in West Africa. JPM MCS, in collaboration with international organizations and other military and civilian health agencies, was integral to stopping the spread of the outbreak and is helping to bring it to an end.
So what did JPM MCS do, and what does it continue to do? These questions span three different areas that are common to any such outbreak, whether caused by Ebola or by an unknown or unexpected disease agent: detection (tests or assays), therapeutics (drugs), and prevention (vaccines).
Beginning in March 2014, through its Diagnostics and Critical Reagents Program teams, JPM MCS made available clinical assays and surveillance test kits to detect the presence of EVD.
The FDA granted Emergency Use Authorization for an assay kit, known as EZ1, on October 5, 2014, and it has since been used by laboratories in the U.S. and foreign locations to support monitoring of returning troops. The test has identified every case of EVD diagnosed in the United States thus far. More than 600 EZ1 kits were fielded, with the majority going to the Centers for Disease Control and Prevention (CDC) for use by participating laboratories in its Laboratory Response Network. The remaining kits have been provided to military facilities, including the U.S. Army Medical Research Institute of Infectious Diseases in Maryland, Landstuhl Regional Medical Center in Germany, medical centers at Fort Hood and Fort Bliss in Texas, Joint Base Lewis-McChord in Washington, and Fort Bragg in North Carolina.
The Critical Reagents Program produces kits used for public health surveillance. These kits — identical to the EZ1 kit except for the FDA labeling and reporting requirements — were among the first made available to West African countries. A collaborative effort involving DoD, international organizations, and nongovernmental organizations made it possible to pre-position resources that enabled the host nation to rapidly respond to events. These partnerships helped set a precedent for successfully responding to a crisis.
Both the EZ1 and the surveillance kits are manufactured at the Naval Medical Research Center, which has kept pace with delivery orders. Stockpiles are being created for the CDC (1,000 EZ1 kits), DoD (300 EZ1 kits), and locations in West Africa (450 surveillance kits).
A different diagnostic tool developed by the Diagnostics team and used in the EVD outbreak is the Next Generation Diagnostics System (NGDS) BioThreat-Ebola (BT-E) diagnostic assay from BioFire Defense. Used on the FDA-cleared FilmArray system, it is a reduced-complexity point-of-care diagnostic tool with fully automated sample preparation. The FilmArray single sample time to result is about 60 minutes. The FDA granted an Emergency Use Authorization for the BT-E diagnostic assay on October 25, 2014.
Through its BioDefense Therapeutics program, JPM-MCS is developing treatments for EVD. The drugs are considered experimental and have been given to infected patients who were evacuated to the U.S. and to Europe. One, favipiravir (also known as T-705), has been used in seven patients; the other, Tekmira Ebola (also known as TKM-Ebola), has been used in six patients. Two critically ill patients received both drugs as part of combination therapy (in which multiple therapies are given). The effectiveness of these drugs is being studied closely.
Favipiravir, an antiviral drug from MediVector Inc., has recently completed Phase 3 clinical trials for influenza. Laboratory studies have shown that it is active against Ebola virus. In November 2014, JPM-MCS awarded a $30 million letter contract to MediVector to support an Investigational New Drug filing and clinical testing of favipiravir as a treatment for EVD.
TKM-Ebola, an antiviral drug from Tekmira Pharmaceuticals Corp., is in Phase 1 clinical trials to evaluate its safety in humans. Its effectiveness against Ebola has been demonstrated in animal models. MCS’s BioDefense Therapeutics program has accelerated the development and production of about 500 treatment courses of TKM-Ebola-Guinea, a related drug that targets the Ebola virus variant responsible for the current outbreak.
Tekmira is also working with the World Health Organization and the International Severe Acute Respiratory and Emerging Infection Consortium to begin a clinical trial in West Africa. While this is a separately funded effort, data collected in these trials will be leveraged for DoD-funded drug development efforts. The foresight and funding from JPM-MCS made these drugs available, but the final decision to actually use them was made by treating physicians, regulatory authorities, and the companies that own the drugs.
Through its Joint Vaccine Acquisition Program (JVAP), JPM-MCS is working in several ways to speed the development of Ebola vaccines. Vaccination programs can turn the tide against an epidemic by containing the outbreak and providing safety to health care workers as they perform vital services. JPM MCS’s prevention objective is to accelerate, as much as possible, the development of vaccine candidates. JVAP and the Defense Threat Reduction Agency, another program within DoD, are co-funding the development of an Ebola vaccine from NewLink Genetics Corp. JVAP is supporting this effort with immunological assays, nonclinical (nonhuman) studies, manufacturing efforts, and subject matter expertise.
In all, 31,000 doses of this vaccine have been produced for clinical trials. Worldwide, there are seven Phase 1 trials under way: two in the United States and one each in Canada, Switzerland, Germany, Gabon, and Kenya. Immunological testing of patients in a Phase 1 clinical trial at the Walter Reed Army Institute of Research is complete, and a vaccine efficacy study in nonhuman primates has begun.
Two other vaccine candidates, for use against both the Ebola virus and a related virus, Marburg, are next in the pipeline and could begin clinical trials in summer of 2015. MCS-JVAP is engaged across U.S. government agencies as it moves forward with the development of all these vaccine candidates. On December 9, 2014, Secretary of Health and Human Services Sylvia Mathews Burwell announced a declaration under the Public Readiness and Emergency Preparedness Act to facilitate the development of experimental Ebola vaccines, providing immunity under U.S. law against legal claims related to the manufacturing, testing, development, distribution and administration of the three Ebola vaccines.
JPM MCS’s mission is to counter chemical, biological, radiological, and nuclear threats to the country and its military forces—threats we hope never become a part of day-to-day life. Should the threats be realized, we have a unique capacity to detect, rapidly respond, and reallocate resources to counter those threats. Our ability to respond to this crisis with pre-positioned state-of-the-art diagnostic resources, the rapid acceleration of drug development, and the release of existing supplies of promising therapeutics for use on a humanitarian basis is a testament to JPM-MCS’s commitment to medical countermeasures development. In future crises, as in the current Ebola outbreak, one of the most important elements of our response will be continued cooperation and collaboration by our military, civilian, and nonprofit medical communities. The tide of this Ebola crisis has been turned back—not because of the efforts of one office or one organization, but by the combined force of military and civilian partners, international organizations, and nongovernmental organizations. The support of our nation’s leaders for the continued development of these assets, military and civilian alike, and the continued collaboration in the field are critical.
About Joint Project Manager Medical Countermeasure Systems (JPM-MCS)
The U.S. Department of Defense’s Joint Project Manager Medical Countermeasure Systems (JPM-MCS) is one of seven JPMs within the Joint Program Executive Office for Chemical and Biological Defense. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance our nation’s biodefense response capability.