Takeda Redacts Dengue Vaccine Application After FDA Requests More Data

Yesterday, Takeda Pharmaceutical Co. announced the withdrawal of a Biologics License Application (BLA) for its dengue vaccine candidate, TAK-003.

Takeda opted to voluntarily rescind the application, reportedly after the US Food and Drug Administration (FDA) requested additional data not included in the phase 3 TIDES trial for TAK-003. The FDA’s requested aspects of data collection “cannot be addressed within the current BLA review cycle,” Takeda stated. “The future plan for TAK-003 in the US will be further evaluated given the need for travelers and those living in dengue-endemic areas of the US, such as Puerto Rico.”

Dengue fever is the world’s most prevalent mosquito-borne disease, actively threatening half of the global population. Dengue is endemic in more than 125 countries, and infection rates are 8 times higher now than they were 20 years ago.

Climate change is a major factor, growing the mosquito population and making vector-borne diseases possible in new regions of the world. Dengue is transmitted by Aedes mosquitoes, and changing climates mean areas outside of the tropics and subtropics have become breeding grounds for the vector.

Individuals traveling to Latin America, Southeast Asia, and the Caribbean are at particularly high risk of dengue fever. However, the disease has recently expanded to Croatia, France, Portugal, and the southern states of the US, thus increasing the need for an approved dengue vaccine.

TAK-003, marketed as Qdenga, is authorized in the European Union, United Kingdom, Brazil, Argentina, Indonesia, and Thailand. After its December approval, TAK-003 became the only dengue vaccine available in the EU for individuals with and without prior dengue exposure.

The approval was based upon the global phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, which met its primary endpoint of vaccine efficacy, preventing 80.2% of symptomatic dengue cases a year after vaccination. TAK-003 also met its secondary endpoint during the TIDES trial, with 90.4% of hospitalizations prevented 18 months after vaccination.

Throughout the 4.5-year follow-up period, TAK-003 prevented 84% of hospitalized dengue cases and 61% of symptomatic infections in the overall population. TAK-003 had a favorable safety profile with no evidence of disease enhancement in seropositive or seronegative individuals who received the vaccine, and no important safety risks.

The TAK-003 vaccine is based on a live-attenuated dengue serotype 2 virus, laying the genetic groundwork for 4 dengue serotypes and protecting against them all. With the EC approval, TAK-003 (Qdenga) is indicated to prevent dengue disease in individuals as young as 4 and living in the EU Member States. The vaccine is administered subcutaneously as 2 0.5 mL doses, given 3 months apart.

The WHO estimates there are 3.1 million cases of mosquito-borne viral infections in the US, with over 25,000 classified as severe. Recently, Florida and Texas reported the US’s first locally acquired malaria cases in 20 years, with 7 confirmed infections.