FDA News

FDA approves Dengvaxia for dengue prevention in children

Peter Marks
Peter Marks

The FDA approved Sanofi Pasteur’s vaccine Dengvaxia to prevent dengue disease caused by all four serotypes in children aged 9 through 16 years who have laboratory-confirmed previous dengue infection. Children living in U.S. territories where dengue is endemic — including American Samoa, Guam, Puerto Rico and the U.S. Virgin Islands — will be eligible for vaccination, the agency said.

Dengvaxia had been previously approved in 19 other countries and the European Union.

Today’s FDA approval was based on the results of three randomized, placebo-controlled studies that included approximately 35,000 participants in several endemic areas, including Puerto Rico, Latin America and the Asia Pacific region. The vaccine was approximately 76% effective in preventing symptomatic and lab-confirmed dengue disease in children who had been infected before vaccination.

Historically, it has been challenging to develop an effective dengue vaccine. Patients infected with one of the four serotypes develop lifelong immunity to that serotype, but these patients are at an increased risk for severe dengue if they become infected with one of the remaining three serotypes. An effective vaccine must prevent infection from all four serotypes.

The FDA noted that the vaccine is not approved for individuals who have not been previously infected with dengue or who have no record of dengue infection. This is because the vaccine appears to act as a first dengue infection, without actually infecting the person with wild-type dengue virus, and could therefore make subsequent infections much more severe.

This phenomenon, triggered by antibody-dependent enhancement, was observed in 2017 during a nationwide immunization program in the Philippines. The program was suspended after data from two phase 3 trials revealed that participants aged 2 to 5 years were five times more likely to be hospitalized for dengue compared with participants who received placebo.

“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,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release.

Before vaccinating, health care providers are urged to evaluate children for prior dengue infection and avoid vaccinating uninfected people. If no medical records of previous dengue infection are available, a patient’s infection status can be determined by serological testing before vaccination, according to the FDA.

“When Dengvaxia is administered in accordance with the FDA-approved prescribing information, the FDA is confident in the safety of Dengvaxia,” an FDA spokesperson told Infectious Diseases in Children.

The CDC estimates that 400 million dengue virus infections occur every year around the world. Approximately 500,000 of these infections progress to dengue hemorrhagic fever (DHF), a more severe form of the illness. DHF causes approximately 20,000 deaths, and most fatalities are reported among children.

“The FDA is committed to working proactively with our partners at the U.S. CDC, as well as international partners, including WHO, to combat public health threats,” Anna Abram, FDA deputy commissioner for policy, legislation and international affairs, said in a press release. “While there is no cure for dengue disease, today’s approval is an important step toward helping reduce the impact of this virus in endemic regions of the United States.” – by Katherine Bortz

Disclosures: Marks and Abram report no relevant financial disclosures.

Peter Marks
Peter Marks

The FDA approved Sanofi Pasteur’s vaccine Dengvaxia to prevent dengue disease caused by all four serotypes in children aged 9 through 16 years who have laboratory-confirmed previous dengue infection. Children living in U.S. territories where dengue is endemic — including American Samoa, Guam, Puerto Rico and the U.S. Virgin Islands — will be eligible for vaccination, the agency said.

Dengvaxia had been previously approved in 19 other countries and the European Union.

Today’s FDA approval was based on the results of three randomized, placebo-controlled studies that included approximately 35,000 participants in several endemic areas, including Puerto Rico, Latin America and the Asia Pacific region. The vaccine was approximately 76% effective in preventing symptomatic and lab-confirmed dengue disease in children who had been infected before vaccination.

Historically, it has been challenging to develop an effective dengue vaccine. Patients infected with one of the four serotypes develop lifelong immunity to that serotype, but these patients are at an increased risk for severe dengue if they become infected with one of the remaining three serotypes. An effective vaccine must prevent infection from all four serotypes.

The FDA noted that the vaccine is not approved for individuals who have not been previously infected with dengue or who have no record of dengue infection. This is because the vaccine appears to act as a first dengue infection, without actually infecting the person with wild-type dengue virus, and could therefore make subsequent infections much more severe.

This phenomenon, triggered by antibody-dependent enhancement, was observed in 2017 during a nationwide immunization program in the Philippines. The program was suspended after data from two phase 3 trials revealed that participants aged 2 to 5 years were five times more likely to be hospitalized for dengue compared with participants who received placebo.

“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,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in a press release.

Before vaccinating, health care providers are urged to evaluate children for prior dengue infection and avoid vaccinating uninfected people. If no medical records of previous dengue infection are available, a patient’s infection status can be determined by serological testing before vaccination, according to the FDA.

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“When Dengvaxia is administered in accordance with the FDA-approved prescribing information, the FDA is confident in the safety of Dengvaxia,” an FDA spokesperson told Infectious Diseases in Children.

The CDC estimates that 400 million dengue virus infections occur every year around the world. Approximately 500,000 of these infections progress to dengue hemorrhagic fever (DHF), a more severe form of the illness. DHF causes approximately 20,000 deaths, and most fatalities are reported among children.

“The FDA is committed to working proactively with our partners at the U.S. CDC, as well as international partners, including WHO, to combat public health threats,” Anna Abram, FDA deputy commissioner for policy, legislation and international affairs, said in a press release. “While there is no cure for dengue disease, today’s approval is an important step toward helping reduce the impact of this virus in endemic regions of the United States.” – by Katherine Bortz

Disclosures: Marks and Abram report no relevant financial disclosures.