Takeda has voluntarily withdrawn the Biologics License Application for its dengue vaccine candidate TAK-003 following discussions with the FDA regarding additional data collection, the Japanese pharma company announced Tuesday.
According to Takeda, it will not be able to address the regulator’s concerns within the current BLA review cycle. The company is currently assessing its future options and plans for TAK-003, as well as evaluating the requirements for a potential BLA resubmission in the U.S., a spokesperson told Fierce Pharma.
The FDA accepted Takeda’s BLA for TAK-003 in November 2022 and put the application under Priority Review, which typically results in a decision within six months versus the standard 10-month review period.
“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 vaccines business unit, said in a statement.
TAK-003 is a tetravalent live-attenuated vaccine candidate that can induce immunity for all four major dengue serotypes. In a large mid-stage trial, Takeda demonstrated that immunization with TAK-003 led to high antibody titers in children and teens, regardless if they were seropositive or seronegative at baseline. The immune response persisted for up to 48 months post-dose.
Takeda followed up the Phase II data with the pivotal Phase III TIDES trial, which met its primary endpoint of overall vaccine efficacy. TIDES enrolled nearly 21,000 participants across several dengue-endemic areas in Latin America and Asia, who were enrolled at a 2:1 ratio to receive either TAK-003 or a placebo.
The study’s primary endpoint is vaccine efficacy and safety calculated through 12 months after the second dose. TAK-003 had a vaccine efficacy of 80.2% against virologically confirmed dengue in the per-protocol analysis and a 95.4% efficacy rate against dengue leading to hospitalization.
At the 17-month follow-up, TAK-003 had an efficacy rate of 90.4% against hospitalized dengue and 85.9% against dengue hemorrhagic fever.
In a statement to Fierce Pharma, the Takeda spokesperson said that the FDA had previously reviewed and approved the trial design for TIDES, but during discussions with the company asked for more data that were beyond the scope of the study.
TIDES is designed in accordance with “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 said in a statement Tuesday.
TAK-003 is approved in Thailand, Indonesia, Argentina, Brazil, the UK and the EU, where it is marketed under the brand name Qdenga.
