May 6, 2019Regulatory
The CDC estimates more than one-third of the world's population is living in areas at risk for infection by dengue virus which causes dengue fever, a leading cause of illness among people living in the tropics and subtropics. The first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu or another viral infection. A subsequent infection can lead to severe dengue, including dengue hemorrhagic fever (DHF), a more severe form of the disease that can be fatal. Symptoms may include stomach pain, persistent vomiting, bleeding, confusion and difficulty breathing. Approximately 95% of all severe/hospitalized cases of dengue are associated with second dengue virus infection. Because there are no specific drugs approved for the treatment of dengue disease, care is limited to the management of symptoms. Each year, an estimated 400 million dengue virus infections occur globally according to the CDC. Of these, approximately 500,000 cases develop into DHF, which contributes to about 20,000 deaths, primarily among children. Although dengue cases are rare in the continental U.S., the disease is regularly found in American Samoa, Puerto Rico, Guam, the U.S. Virgin Islands, as well as Latin America, Southeast Asia and the Pacific islands.
The FDA has approved Dengvaxia, the first vaccine approved for the prevention of dengue disease caused by all dengue virus serotypes (1, 2, 3 and 4) in people ages 9 through 16. Dengvaxia has already been approved in 19 countries and the European Union. People eligible for the vaccine should have laboratory-confirmed previous dengue infection and live in endemic areas. According to the FDA, infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease, which may lead to hospitalization or even death. FDA added that as the second infection with dengue is often much more severe than the first, the FDA's approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease.
The safety and effectiveness of the vaccine was determined in three randomized, placebo-controlled studies involving approximately 35,000 individuals in dengue-endemic areas, including Puerto Rico, Latin America and the Asia Pacific region. The vaccine was determined to be approximately 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in individuals 9 through 16 years of age who previously had laboratory-confirmed dengue disease. The most commonly reported side effects by those who received Dengvaxia were headache, muscle pain, joint pain, fatigue, injection site pain and low-grade fever. The frequency of side effects was similar across Dengvaxia and placebo recipients and tended to decrease after each subsequent dose of the vaccine.
Dengvaxia is not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. This is because in people who have not been infected with dengue virus, Dengvaxia appears to act like a first dengue infection - without actually infecting the person with wild-type dengue virus - such that a subsequent infection can result in severe dengue disease. Therefore, health care professionals should evaluate individuals for prior dengue infection to avoid vaccinating individuals who have not been previously infected by dengue virus. This can be assessed through a medical record of a previous laboratory-confirmed dengue infection or through serological testing (tests using blood samples from the patient) prior to vaccination.
Dengvaxia is a live, attenuated vaccine that is administered as three separate injections, with the initial dose followed by two additional shots given six and twelve months later
The FDA granted this application Priority Review and a Tropical Disease Priority Review Voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of certain tropical diseases. The approval was granted to Sanofi Pasteur.