The Food and Drug Administration on Wednesday approved the first vaccine against dengue fever, one that protects against a common disease but has generated significant controversy due to evidence it can increase the risk of severe infection in some people.
The agency ruled that Dengvaxia, manufactured by Sanofi (SNY) Pasteur, can only be used in individuals aged 9 to 16 living in parts of the United States where the dengue virus is endemic — in other words, where it circulates on an ongoing basis. Dengue is found only in Puerto Rico and a few other U.S. offshore territories and protectorates.
Furthermore, the vaccine can only be given to children and teens who have had one previous laboratory-confirmed case of dengue.
The various restrictions mean the U.S. market for the vaccine is smaller still than the already modest market Sanofi had sought. Still, the company said it was pleased by the FDA’s decision.
“Today’s FDA approval of Dengvaxia allows us to bring a critical medical prevention tool to at-risk populations, helping combat and prevent dengue, particularly among children, in U.S. dengue-endemic areas,” Dr. David Greenberg, Sanofi’s regional medical head for North America, said in a statement.
Late last year, the European Commission approved the vaccine for use in dengue endemic parts of Europe — mainly offshore territories, such as the Caribbean islands of Martinique and Guadeloupe. The approval allows for use of the vaccine in people ages 9 to 45 who have previously had at least one dengue infection.
Regulators have sought to restrict access to Dengvaxia following post-marketing research by Sanofi that showed that, while the vaccine offers protection for people who have already had at least one bout of dengue, it increases the risk of severe infection in children who were dengue-naïve — that is, never infected — when they were vaccinated.
There are four serotypes of dengue viruses, numbered 1 through 4. Infection with one virus does not protect against the others and actually appears, for a time, to increase the risk that another dengue infection will trigger a severe form of the disease that can be life threatening. That phenomenon is called antibody-dependent enhancement, or ADE.
After Sanofi announced its findings, the Philippines — the only country to have used the vaccine broadly to date — suspended use of Dengvaxia and ultimately revoked its license. Prosecutors have charged Sanofi, a half-dozen of its employees, and several current and former Philippines health officials over a series of deaths it alleges are linked to use of the vaccine.
Based on the company’s findings, experts who advise the World Health Organization on vaccine policy recommended that Dengvaxia only be given to people who are known to have had a previous infection.
Identifying those people is currently a challenge. Many dengue infections are mild and go undiagnosed, so lack of a confirmed dengue case on a child’s medical record cannot be taken as proof the child was never infected. Testing is needed — but at present there is no rapid point-of-care test to administer.
Sanofi officials have said they hope to have such a test ready to submit for approval to the FDA by late 2020.
Dengvaxia is licensed for use in 19 countries, plus the eligible parts of the European Union. Sanofi said the vaccine is currently available in 10 countries in Latin America and Asia.
Despite the restrictions placed on the vaccine by the FDA, by bringing to market a product to protect against dengue fever, Sanofi will earn a priority review voucher — an incentive created to encourage pharmaceutical companies to develop drugs and vaccines that can treat or protect against diseases for which market forces alone don’t spur development.
A company can use a voucher to expedite the review of another product it hopes to bring to market or it can sell it to another pharmaceutical firm. Since the priority review voucher program was initiated about a decade ago, roughly two dozen vouchers have been issued; vouchers that have been sold recently earned prices of between $80 million to $130 million.