Takeda announced Tuesday that it has voluntarily withdrawn its application to the Food and Drug Administration for its dengue vaccine, making it unclear when or if the vaccine will be licensed in this country.
The company said in a press release that it will review whether to proceed with trying to bring the vaccine to the U.S. market. The vaccine has already been approved in the European Union, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand.
“The urgent global need to combat the growing burden of dengue remains, and we will continue to progress regulatory reviews and provide access for people living in and traveling to dengue-endemic areas while we work to determine next steps in the U.S.,” Gary Dubin, president of Takeda’s global vaccines business unit, said in a statement.
Currently there is only one dengue vaccine licensed in the U.S., GSK’s Dengvaxia. But it is only licensed for use in children and teens aged 6 to 16 living in dengue-endemic areas — principally Puerto Rico — who have previously had a laboratory-confirmed case of dengue. It cannot be used as a travel vaccine, for people living on the U.S. mainland who are traveling to areas of the world where dengue spreads.
Dengue has been a challenging virus to develop a vaccine against, because of a peculiarity of the virus. There are four serotypes of dengue, numbered 1 through 4. Infection with one does not protect against infection by another. And, in fact, in some cases a previous exposure to dengue — through infection or vaccination — can lead to more serious disease on the second or subsequent infections.
The Takeda press release stated that the company’s decision was based on the fact that the FDA asked for additional data that were not captured by the clinical trial for the vaccine. It further said that the agency had previously reviewed and accepted the trial protocol.
Takeda declined STAT’s request for an interview and did not specify what additional information the FDA was seeking.
Dengue is nicknamed breakbone fever, because of the painful infection it triggers. Transmitted by Aedes aegypti mosquitoes, it’s estimated that nearly 100 million to 400 million people a year are infected with dengue, which is found in much of Asia, Africa, and Latin America.
A small portion of people who contract the disease develop a severe form — dengue hemorrhagic fever — which can be fatal. It’s estimated that about 500,000 people develop severe dengue each year and about 22,000 die.
In most of the United States, dengue is not frequently diagnosed. In the first five months of this year, there were 129 dengue cases reported, only three of which were thought to have been locally acquired. In Puerto Rico, where dengue is endemic, 256 cases were reported from the start of the year through June 1.
The virus is found in more than 100 countries around the globe, according to the World Health Organization.
There have been some concerns about the performance of Takeda’s vaccine, which is a two-dose vaccine with shots spaced three months apart. The Phase 3 clinical trial found a lack of efficacy against dengue 3 in children who were sero-negative — those who had never previously been infected with dengue. And there were too few cases of dengue 4 to determine if the vaccine was effective against it.
A spokesperson said Takeda is not concerned that the decision to withdraw the application from the FDA will hurt the reputation of the vaccine or affect its chances of being approved elsewhere.
“Takeda’s decision to withdraw the application for TAK-003 in the U.S. is not expected to have a material impact on the full year consolidated reported forecast for the fiscal year ending March 31, 2024,” the spokesperson said via email.
“More broadly, the withdrawal will have no impact on the label in countries that have approved the vaccine, nor will it change the indication that we seek. We will continue to progress regulatory filings in dengue-endemic and non-endemic countries globally.”
The clinical trial to support the licensure application enrolled 20,000 people from eight dengue-endemic areas in Latin America and Asia.