The U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for the expansion of the indication for ACAM2000, (Smallpox and Mpox (Vaccinia) Vaccine, Live) to include prevention of mpox disease in individuals at high risk for mpox infection.
The approval is based on previously available human safety data and data from a well-controlled animal study in which ACAM2000 vaccine was shown to be effective in protecting against mpox virus exposure.
Emergent’s ACAM2000 is a single-dose vaccine administered percutaneously via a bifurcated needle that is dipped into the vaccine solution and the skin is pricked several times in the upper arm with a droplet of the vaccine.
The vaccine was first approved by the FDA in 2007 for active immunization for the prevention of smallpox disease in individuals determined to be at high risk for smallpox infection.
Mpox, previously called monkeypox, is an infectious disease endemic to central and west Africa caused by the double-stranded DNA mpox virus. The virus is a member of the Orthopoxvirus genus in the Poxviridae family, related to the virus which caused smallpox, which was eradicated in 1980.
“The FDA approval of ACAM2000 for immunization against mpox in high-risk individuals further strengthens and broadens our industry-leading smallpox portfolio, which includes VIGIV and TEMBEXA,” says Joe Papa, president and CEO of Emergent, in a news release. “This expanded indication for ACAM2000 comes at a critical time as the global health community comes together to ensure an effective and cohesive response to the recent upsurge in mpox cases. We believe Emergent is poised to support the global response needed by actively engaging with world health leaders, as well as deploying product currently available in inventory based on the needs, as well as the ability to increase supply.”
This approval follows Emergent’s announcement that it filed an Expression of Interest (EOI) with the World Health Organization (WHO) for the WHO’s assessment of ACAM2000 vaccine to be added as an Emergency Use Listing in connection with the mpox outbreak. Emergent also is in discussions with other global public health leaders to help address the current mpox outbreak in response to the WHO’s Director-General’s August 14 statement declaring that the upsurge of mpox is a public health emergency of international concern under the International Health Regulations.
As part of its support to the response, Emergent announced that it will donate 50,000 doses of ACAM2000 for potential deployment across impacted countries in Central Africa.
“Mpox has progressed to become an uncontrolled epidemic in Africa — prompting the WHO to declare a second public health emergency of international concern — creating an enormous need to use all effective tools to extinguish it as a threat,” says Dr. Amesh A. Adalja, FIDSA FACP FACEP & health security and emerging infectious diseases expert, Johns Hopkins Center for Health Security. “ACAM2000, a direct descendant of the Jenner vaccine (humanity’s first) which was used to eradicate smallpox, and now with the broadened indication, will be an invaluable tool in this endeavor.”
In 2022, the world experienced a global outbreak of clade II mpox, which led to more than 95,000 cases across 115 non-endemic countries.
The clade I variant of mpox is characterized by more severe clinical outcomes and a higher case fatality rate. The recently identified clade Ib variant, exhibiting enhanced transmissibility through close contact, has led to an increase in cases, particularly in Central Africa, and a sizable impact on children and families. According to the WHO, clade I mpox tends to cause a higher number of severe infections and have a higher mortality rate than clade II mpox.
ACAM2000 is indicated in the U.S. for active immunization for the prevention of smallpox and mpox disease in individuals determined to be at high risk for smallpox and mpox infection.
The labeling for ACAM2000 contains a contraindication for individuals with severe immunodeficiency. Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems. Individuals with severe immunodeficiency who are not expected to benefit from the vaccine should not receive ACAM2000®. The risk for experiencing severe vaccination complications must be weighed against the risk for experiencing a potentially severe or fatal smallpox or mpox infection.
Additionally, there are warnings and precautions for myocarditis, pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson Syndrome), eczema vaccinatum resulting in permanent sequelae or death, accidental eye infection (ocular vaccinia), which can cause ocular complications that may lead to blindness, and fetal death. These may occur following either primary vaccination or revaccination with live vaccinia virus vaccines, including ACAM2000. These risks are increased in certain individuals and may result in severe disability, permanent neurological sequalae and/or death.
