Non-replicating smallpox vaccine
IMVAMUNE® is approved in Canada and in the European Union (marketed under the trade name IMVANEX®. Phase 3 registration trials have been successfully concluded in the U.S. and filing of a BLA is expected in second half of 2018.
IMVAMUNE is a non-replicating smallpox vaccine distributed in liquid-frozen formulation, suitable for use in people for whom replicating smallpox vaccines are contraindicated (e.g. people with HIV and atopic dermatitis). The vaccine is the only non-replicating smallpox vaccine approved in Europe for use in the general adult population. Although not yet approved in the United States, IMVAMUNE is currently stockpiled by the U.S. Government for emergency use in people for whom replicating smallpox vaccines are contraindicated. Registration studies to support FDA approval for use of the vaccine in the entire population have been concluded and submisson of a BLA is expected in second half of 2018.
Traditional smallpox vaccines are based on replicating vaccinia virus strains. Although these vaccines have been effective in preventing the disease, their use may be associated with an increased risk of adverse events, including death and severe disability.
IMVAMUNE is based on MVA-BN® (a strain of the Modified Vaccinia Ankara virus). It is injected like other modern vaccines rather than pricked into the skin with a bifurcated needle. While the MVA-BN virus is highly attenuated and is thus incapable of replicating in the body, it is still capable of eliciting a potent immune response and does so without producing the post-vaccination complications associated with traditional smallpox vaccines.
Although the World Health Organization (WHO) declared smallpox eradicated in 1980, this contagious and deadly disease remains high on the list of possible bioterror threats. Unique to humans, the disease is caused by the Variola virus and transmitted from person to person through direct contact with contaminated fluids and objects, as well as through the air. Historically, about 30% of those who became infected with smallpox died from the illness. There is currently no cure for the disease, vaccination is the only proven protection.
The U.S. government considers smallpox a material threat to national security. National security concerns are based on intelligence regarding previous biological weapons programs, coupled with the infectivity of the virus, an increasingly vulnerable population due to lack of immunity, and the relative ease of large-scale production. In fact, the U.S. Department of Defense has a mandatory smallpox vaccination program for troops being deployed to certain areas around the globe.
While the only known samples of smallpox are held at secure labs in the U.S. and Russia, the U.S. National Research Council found in a 2008 report that "the creation or acquisition of smallpox is well within the technical reach of a determined and well-resourced terrorist."
Given today's global travel and the virus' long incubation period, all nations must safe-guard against this virus. A smallpox outbreak anywhere could quickly become a global, not a local, problem.
The U.S. Government has a long-term strategy to provide sufficient non-replicating smallpox vaccine to protect 66 million people, representing 132 million doses of IMVAMUNE, to address those for whom a replicating smallpox vaccine is contraindicated or who have severe immunodeficiency and who are not expected to benefit from the vaccine. These individuals include severely immuno-compromised individuals and the following individuals who are otherwise at increased safety risk: pregnant women; individuals with HIV infection; individuals with a history of eczema or atopic dermatitis; individuals who are undergoing bone marrow transplantation or individuals with primary or acquired immunodeficiency who require isolation; or infants less than one year of age.
As part of this strategy, we were awarded a contract in 2009 to develop a freeze dried formulation of IMVAMUNE, which we believe indicates the U.S. Government's desire to develop an improved formulation of IMVAMUNE to replace the liquid-frozen formulation of IMVAMUNE currently stockpiled in the SNS. The freeze-dried formulation has a potential shelf life of 5+ years and would also simplify the storage and shipping logistics.
We have generated the clinical data required to support stockpiling of this next generation of the vaccine in the SNS and are on track to validate the production process, which remains the final step towards meeting the overall U.S. regulatory requirements for the freeze-dried version of the vaccine.