In August, 2014, BARDA responded to the Ebola epidemic by working with our PHEMCE and industry partners to transition early stage therapeutic and vaccine candidates (supported by NIH and DoD) into BARDA’s advanced development programs.
Under the Project BioShield Act (2004) (PDF - 191 KB), Pandemic and All-Hazards Preparedness Act (2006) (PDF -248 KB), and Pandemic and All-Hazards Reauthorization Act (2013) (PDF - 284 KB), BARDA’s strategy to support advanced development of critical medical countermeasures (MCMs) targets biothreats that have been determined by the Department of Homeland Security as Material Threats. The material threat determinations for Ebola and Marburg were issued in September, 2006. The Ebola epidemic of 2014-2015 in the West African countries of Guinea, Liberia and Sierra Leone demonstrates that this virus is also an emerging infectious disease. BARDA’s Ebola MCM strategy for development, manufacturing and evaluation of monoclonal antibody and antiviral drug therapeutic candidates has three goals: make clinical trial materials with industry partners, ensure safety and efficacy evaluation in animal or clinical studies, and support improved product manufacturing toward FDA approval.
In August, 2014, BARDA responded to the Ebola epidemic by working with our PHEMCE and industry partners to transition early stage therapeutic and vaccine candidates (supported by NIH and DoD) into BARDA’s advanced development programs. This filled the last gap in BARDA’s CBRN MCM development programs. BARDA is supporting the advanced development of six (6) monoclonal antibody candidates and one (1) antiviral drug candidate for treatment of Ebola. ZMapp (Mapp Biopharmaceutical), which is formulated and filled by BARDA’s Fill Finish Manufacturing Network, is a tobacco-based monoclonal antibody cocktail currently under clinical evaluation for safety and efficacy to use as a therapeutic in West Africa. Other Ebola monoclonal antibody candidates from Regeneron and Genentech (partnered with BARDA) are utilizing specialized Chinese Hamster Ovary (CHO) cells and other monoclonal antibody technologies. These new monoclonal antibody candidates are in nonhuman primate challenge studies for safety and efficacy using BARDA’s Nonclinical Studies Network, and manufacturing of future clinical investigational lots is planned at BARDA’s Centers for Innovative Advanced Development and Manufacturing (CIADMs). Additionally, the Ebola antiviral drug candidate BCX4430 (BioCryst) transitioned from NIH is now in Phase 1 dose-ranging pharmacokinetics/pharmacodynamics studies in the U.S.
BARDA’s investment in Ebola therapeutics also is bolstered by support for advanced development of diagnostic tests and platform technologies. Rapid, accurate diagnostic tests can facilitate early warning, outbreak control and targeted therapeutic drug therapy for infected patients. The rapid and coordinated support for development of Ebola diagnostic, therapeutic and vaccine candidates demonstrates the effectiveness of leveraging BARDA’s programs together with the new National MCM Response Infrastructure to respond to today’s crisis and prepare for future Ebola and unknown emerging infectious disease epidemics.
Under the Project BioShield Act (2004) (PDF - 191 KB),BARDA was charged with developing medical countermeasures to address biothreats to the United States determined by the Department of Homeland Security as Material Threats. Since Ebola is both a bioterrorism threat and an emerging infectious disease, the Pandemic and All-Hazards Preparedness Act (2006) (PDF -248 KB), directs BARDA to support advanced development of medical countermeasures for this threat. Established in 2014, BARDA’s Ebola Vaccines Program as part of the U.S. Ebola response focuses on the advanced development, manufacturing, and clinical evaluation of vaccine candidates through collaborations with federal and industry partners. The Program's immediate main goals are to ensure the availability of vaccine investigational lots for clinical trials; support these clinical trials for safety, immunogenicity and efficacy with technical expertise and BARDA’s Clinical Studies Network; transition vaccine manufacturing from pilot to commercial scale; and develop more thermostable vaccines for easier usage and longer storage. The long-term goal of the Ebola Vaccines Program is to support advanced development and procurement of multivalent vaccines effective for prevention of multiple strains of Ebola viruses and Marburg virus.
BARDA is supporting in 2015 the advanced development of three (3) Ebola vaccine candidates with several more under consideration. These vaccine candidates include live, attenuated virus vaccines using recombinant adenovirus and vesicular stomatitis virus vectors to express the Ebola G protein. Phase 1 clinical studies on two of these vaccine candidates show they are well tolerated and immunogenic. The program is making rapid progress with these vaccine manufacturers by ensuring clinical investigational lots of vaccine are available, transitioning manufacturing from pilot to commercial scale to increase production capacity, and testing freeze-dried vaccine formulations to increase stability. With its Clinical Studies Network and technical staff, BARDA is aiding CDC to conduct the Ebola vaccine clinical trial that started in April, 2015 in Sierra Leone, testing safety, immunogenicity and efficacy while also addressing logistical issues of frozen vaccine shipping, storage and distribution.
Provided the vaccine(s) are shown to be safe and efficacious, BARDA’s Ebola Vaccines Program and Clinical Studies Network, working with international partners, may enable potential mass vaccination campaigns in West Africa to reduce the current Ebola epidemic to zero cases. Ultimately, the Ebola Vaccine Program’s continued success will provide safe and effective vaccines to protect against the next Ebola outbreak (across the world and the United States) from man-made and natural viral hemorrhagic fever virus threats.