Hundreds of thousands of Americans could be protected from or treated for Ebola infections through the first purchase of vaccines and therapeutic drugs by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services. The vaccines and drugs are the first for Ebola to receive Project BioShield funding which supports late-stage development toward licensure and stockpile purchases.
“Today we are prepared to add four Ebola countermeasures to the stockpile whereas three years ago, very few products were even in early stages of development,” BARDA Director Rick Bright, Ph.D., said. “This marks a pivotal moment in U.S. and global preparedness for future public health emergencies from viral hemorrhagic fevers like Ebola. We reached this point at unprecedented speed, and that’s a direct result of innovative approaches to product development and to partnering across the U.S. government, other nations, and private industry.”
Ebola is considered a potential bioterrorism threat by the U.S. Department of Homeland Security as well as a naturally occurring public health threat. Natural Ebola outbreaks occur most often in African countries, the most recent, from 2014 through 2016. According to the World Health Organization, during that outbreak more than 28,600 cases of Ebola virus infection were suspected, probable or confirmed and more than 11,000 people died.
Under the agreements announced today, BARDA will provide Project BioShield funding for each company to validate its manufacturing processes and undertake the final preparations necessary to apply for approval through the U.S. Food and Drug Administration (FDA). While that work is completed, BARDA can purchase the vaccines and drugs for potential use in a public health emergency.
BARDA could purchase up to 1.13 million regimens of vaccine, including a single-dose vaccine from Merck Sharp & Dohme Corp of Whitehouse Station, New Jersey, and a two-dose vaccine from Janssen Vaccines and Prevention B.V. of Leiden, The Netherlands. In addition, BARDA will purchase a therapeutic drug from Mapp Biopharmaceutical, Inc. of San Diego, California, and a therapeutic drug from Regeneron Pharmaceuticals, Inc. of Tarrytown, New York.
Merck Sharp & Dohme Corp’s single-shot vaccine would be used to protect people who are at high risk of exposure to Ebola. BARDA will provide $39.2 million for late stage development and purchase. The vaccine showed potential efficacy during testing in Guinea, West Africa, using a ring-vaccination protocol. This approach aims to stop the spread of a virus by vaccinating everyone a patient came in contact with and everyone who came in contact with the patient’s contacts.
The Public Health Agency of Canada supported the vaccine’s discovery and partnered with the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, and the U.S. Department of Defense to fund early development. BioProtection Systems Corporation continued the vaccine’s development with support from NIAID, BARDA, DoD, and international partners. Merck Sharp & Dohme Corp now will take additional steps necessary to apply for licensure of the vaccine through the FDA.
Janssen Vaccines and Prevention B.V.’s vaccine is a two-dose vaccine regimen that would be used to prevent illness in people who have not been exposed to Ebola but could be, such as health care workers and the general public. The regimen requires an initial vaccine which is protective against Ebola, followed by a second vaccine that uses different technology and boosts the body’s immune response. This two-dose approach has progressed into multiple Phase 3 studies and demonstrated efficacy in animal models.
This vaccine also received early funding from NIAID to conduct clinical studies in Guinea and Liberia and transitioned to BARDA’s advanced research and development program. Now BARDA will provide $44.7 million for late-stage development and purchase under Project BioShield.
Under the agreement with Mapp Biopharmaceutical, BARDA will initially provide $45.9 million for late-stage development and initial purchase of the therapeutic drug ZMapp™ under Project BioShield. ZMapp is a combination of three monoclonal antibodies. Monoclonal antibodies bind certain proteins in the virus cell to neutralize the virus, decreasing the amount of the virus in the body that the patient’s immune system has to fight.
ZMapp was shown to reduce mortality in guinea pigs and nonhuman primates exposed to Ebola viruses. ZMapp was manufactured for a Phase 1/2 clinical trial during the 2014-2016 Ebola epidemic and used to treat 36 patients with a separate control arm of 35 patients. ZMapp continues to be available and, through an expanded access protocol in the United States and West Africa, the company can collect clinical data when the product is used.
The Defense Threat Reduction Agency (DTRA) within the Department of Defense and the NIAID supported initial work on ZMapp. To speed the drug’s development, BARDA worked closely with those agencies and then worked separately with the company to optimize and accelerate the manufacturing of ZMapp.
In addition, BARDA will initially provide $40.4 million for late-stage development and an initial purchase of REGN3470-3471-3479 from Regeneron Pharmaceuticals, Inc. Regeneron Pharmaceuticals, Inc.’s therapeutic is a monoclonal antibody drug manufactured using specialized CHO mammalian (Chinese hamster ovary) cells. Regeneron Pharmaceuticals, Inc. used its proprietary technology to accelerate the drug’s development timeline from rapid candidate identification to large scale manufacture and can produce large quantities of the drug quickly in an emergency.
Final development and purchase of the new Ebola vaccines and therapeutic drugs under Project BioShield are part of ASPR’s efforts to prepare the nation for Ebola and other severe, highly infectious biothreats, either natural or man-made.
To provide the necessary vaccines and drugs to prevent or treat Ebola and other biothreats, BARDA maintains a comprehensive integrated portfolio approach to advanced research and development, innovation, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, diagnostic tools, and non-pharmaceutical products for public health emergency threats. These threats include pandemic influenza, chemical, biological, radiological, and nuclear agents, emerging infectious diseases, and antimicrobial resistant pathogens.
ASPR and other federal agencies collaborate as a Public Health Emergency Medical Countermeasure Enterprise to prioritize and develop medical countermeasures needed to save lives in disasters and public health emergencies. Through this collaborative body, potential products transition from basic research and early clinical trials at one agency, such as NIAID, to BARDA for the advanced development necessary for a private company to apply for FDA approval or licensure.
HHS is the principal federal agency for protecting the health of all Americans and providing essential human services, especially for those who are least able to help themselves. ASPR leads HHS in preparing the nation to respond to and recover from adverse health effects of emergencies, supporting communities’ ability to withstand adversity, strengthening health and response systems, and enhancing national health security.
For more information on public health and medical preparedness, visit www.phe.gov and to learn more about partnering with BARDA in medical countermeasure development visit www.medicalcountermeasures.gov.