Three companies scrambling to develop Ebola vaccines today offered updates on their progress toward advancing their candidates to human trials.
NewLink Genetics said it won FDA approval to proceed to Phase I clinical trials for the experimental Ebola vaccine, licensed from its initial developer, the Public Health Agency of Canada (PHAC), by the NewLink subsidiary BioProtection Systems.
Separately, Johnson & Johnson will team up with Bavarian Nordic and the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to develop an Ebola vaccine quickly enough to start clinical trials in humans early next year, those companies said.
J&J said its vaccine program would be a combination prime-boost regimen, using one vector to prime and another to boost immune response. The treatment would combine two vaccine components using AdVac® technology from Crucell, one of J&J’s Janssen pharmaceutical companies; and Bavarian Nordic’s MVA-BN® technology.
AdVac® technology involves the development and manufacture of vectors made from adenoviruses such as AD35. Genetic material encoding for viruses, parasites or bacteria can be inserted into the vectors to make vaccines designed to fight human pathogens.
MVA-BN (Modified Vaccinia Ankara—Bavarian Nordic) is designed to address a wide variety of infectious diseases, including biological threats. Bavarian Nordic has manufactured and supplied more than 20 million doses of an MVA-BN-based smallpox vaccine, IMVAMUNE, to the U.S. Strategic National Stockpile.
To date, more than 1,000 people have received Crucell's adeno-platform based vaccine in clinical trials, while Bavarian Nordic’s platform is the basis of the smallpox vaccine registered in Canada and Europe, and used safely in more than 7,300 humans, according to the companies.
The combo regimen will target the Zaire species of Ebola, which is linked to the outbreak in West Africa that has killed more than 1,500 people, and been declared a public health emergency of international concern by the World Health Organization (WHO).
According to J&J, the combination vaccine provided complete protection of vaccinated macaques against disease and death after exposure to a highly virulent wildtype Ebola Zaire strain. The study, conducted under NIAID’s vaccine preclinical services program, demonstrated proof of concept for the prime-boost regimen. Based on those results, Bavarian Nordic, Crucell and NIAID agreed to advance this development program to allow for initiation of a human trial in early 2015.
The Ebola program is an outgrowth of preventive vaccines against Ebola and other filoviruses now under development by Crucell and Bavarian Nordic—which said separately that it has worked with NIAID for several years to advance MVA-BN® toward development of a combined vaccine against Ebola and Marburg viruses.
Bavarian Nordic said it was concurrently developing additional Ebola vaccine candidates, now in preclinical testing. Among them is a multivalent vaccine designed to protect against both Zaire and Sudan strains of Ebola, as well as Marburg. The company is in talks with NIAID to accelerate the development of the multivalent vaccine into a clinical Phase I study in the next 12 months.
J&J said the vaccine was part of a multi-pronged response to Ebola that includes “intensive” review of known pathways linked to Ebola, to determine whether previously-tested medicines can help patients survive an infection; and additional unspecified support to the non-profit organization Direct Relief International, toward air transport of infection prevention products to Liberia and Sierra Leone.
“Our primary goal in this escalating Ebola epidemic is to assist governments in protecting health care workers, families and populations who are at high risk of being infected with Ebola as soon as possible in an effort to stop the disease from spreading further," Paul Stoffels, M.D., J&J’s CSO, said in a company statement.
News of the J&J/Bavarian Nordic Ebola combo regimen was the second disclosure in as many weeks by a major pharma about efforts to develop an Ebola vaccine.
On August 28, GlaxoSmithKline (GSK) said it was preparing to test its own experimental Ebola vaccine on healthy volunteers in the U.K., The Gambia, and Mali starting in mid-month, using more than $4.6 million in funding from an international consortium.
GSK said its vaccine will be tested in Phase I safety trials being co-developed by the pharma giant and the NIH. Those trials will be launched alongside similar studies in the U.S. by NIAID.
NIAID is also studying the experimental Ebola vaccine advanced by NewLink, which said it is working with the U.S. Department of Defense's Defense Threat Reduction Agency (DTRA) and the Walter Reed Army Institute of Research (WRAIR) to launch the initial Phase I safety trial for its vaccine candidate.
The Phase I study will evaluate how healthy adults respond to various doses of vaccine. At the highest doses planned for the trial, NewLink said, the vaccine has worked rapidly enough to be effective in non-human primates even when given after animals were challenged with lethal doses of Ebola virus.
The vaccine is directed at the protein which forms the outer coat of Ebola virus and has been shown to induce antibodies that neutralize the virus. Roughly 40 healthy volunteers will be immunized and then followed to determine the safety of the vaccine and the magnitude and durability of any immune response, including whether these volunteers develop the same levels of antibody responses that are thought to protect monkeys in Ebola challenge studies.
NewLink said it anticipates co-conducting additional Phase I studies to examine different dosing schedules and extension to vulnerable populations, along with NIAID, PHAC, and the WHO.
The company has formed a steering committee among its partners designed to identify and create the scientific, regulatory, and ethical framework needed to proceed quickly with development of its vaccine candidate.
“We are preparing for Phase I studies in North America, Europe, and Africa, and recently signed agreements with third-party manufacturers to scale up vaccine production," said Charles Link, M.D., NewLink’s CEO and CSO. "NewLink's team will be in Geneva this week at the WHO Ebola meeting to continue the process of sharing information and planning for additional studies," he added.