UPDATED: Takeda yanks FDA filing for dengue vaccine, citing data disagreement with regulator

U.S. travelers and healthcare providers looking for another—and potentially safer—dengue vaccine will have to keep waiting. 

After a protracted review, Takeda has decided to withdraw the application for its dengue vaccine candidate, TAK-003, from the FDA, the Japanese company said Tuesday.

The decision comes after the FDA sought additional data that were not captured by the phase 3 TIDES trial used for the application, a Takeda spokesperson told Fierce Pharma. The company figured it couldn’t satisfy the agency’s needs within the current review cycle.

Takeda is exploring all options and will need time to fully evaluate the requirements for a resubmission in the U.S., the company spokesperson said. 

“The future plan for TAK-003 in the U.S. will be further evaluated given the need for travelers and those living in dengue-endemic areas of the U.S., such as Puerto Rico,” Takeda said in a statement.

TAK-003, also known as Qdenga, is already approved in Europe, the U.K., Brazil, Argentina, Indonesia and Thailand. Takeda will continue to seek approvals for Qdenga elsewhere as it works to determine the next steps in the U.S., Gary Dubin, M.D., president of Takeda’s vaccines business unit, said in a statement Tuesday.

Takeda has been counting on the two-dose dengue shot as a growth driver as it deals with costly patent expirations in its pharma portfolio. Targeting launches in 25 countries, Takeda recently updated its peak sales estimate for the vaccine to between $1.6 billion and $2 billion, up from a previous target of $700 million to $1.6 billion. The company has also started making capacity expansions in anticipation of strong demand.

The vaccine is intended to be an improvement on Sanofi’s scandal-laden Dengvaxia, which after a safety scare, has been restricted to use in children 6 to 16 years of age with evidence of previous dengue infections and who live in endemic areas. By comparison, Qdenga hasn’t shown the serious amplification of dengue in people not previously infected by the dengue virus.

The FDA in November put Qdenga’s application under priority review, which should have taken less than six months to complete, compared with 10 months for a standard review. The multi-year TIDES trial has given at least one dose of Qdenga to more than 20,000 individuals. Such a large trial naturally requires more time to review, the Takeda spokesperson noted.

Clinical trials of most drugs and vaccines supporting FDA approvals are mainly conducted in the U.S. and Europe. The phase 3 TIDES trial used for Qdenga’s application was run in several less well-off, dengue-endemic regions in Latin America and Southeast Asia.

The FDA did not raise any concerns during its inspections of clinical trial sites but wanted more data that were not incorporated into the TIDES trial design, the company spokesperson said. The agency previously reviewed and accepted the trial design.

The trial was designed to “account for the complex global nature of dengue,” Dubin said in a statement.

“The study was designed per World Health Organization (WHO) guidance for a second-generation dengue vaccine, and it considered the need to achieve high levels of subject retention and protocol compliance in endemic regions,” Takeda pointed out.

In a long-term exploratory analysis of the TIDES trial, Qdenga prevented 84% of hospitalizations and 61% of symptomatic dengue illness after four and a half years. In the original primary analysis, the vaccine was about 80% effective against virologically confirmed dengue cases at 12 months.

Editor's note: The story has been updated with additional comments from a Takeda spokesperson about the nature of the FDA's request.