Long-term data strengthen TAK-003 potential against dengue

The live-attenuated tetravalent dengue vaccine TAK-003 showed cumulative long-term efficacy in preventing symptomatic dengue caused by all four dengue virus (DENV) serotypes among previously exposed children and adolescents, and by DENV-1 and DENV-2 in dengue-naïve participants in eight* dengue-endemic countries, a study has shown.

Overall, the vaccine’s cumulative efficacy was 61.2 percent against virologically confirmed dengue and 84.1 percent against hospitalized virologically confirmed dengue from the first dose to up to 4.5 years after the second dose.

When stratifying by serostatus, cumulative efficacy against virologically confirmed dengue was 64.2 percent among dengue-exposed participants and 53.5 percent (45.4 percent [DENV-1] and 88.1 percent [DENV-2]) among those who were dengue-naïve.

For hospitalized virologically confirmed dengue, the corresponding efficacies were 85.9 percent in the dengue-exposed group and 79.3 percent (78.4 percent [DENV-1] and 100 percent [DENV-2) in the dengue-naïve group. [Lancet Glob Health 2024;12:e257-e270]

“Assessing vaccine efficacy against virologically confirmed dengue and hospitalized virologically confirmed dengue for all four DENV serotypes can be difficult owing to the erratic and unpredictable nature of dengue epidemiology; however, we were able to collect data for all four serotypes in this trial, albeit limited in some subgroups,” the researchers said.

Favourable safety

“TAK-003 also demonstrated a favourable safety profile during part 3 of the trial (about 22–57 months after the first vaccine),” the researchers said. The rates of serious adverse events (AEs) were similar between the TAK-003 and placebo arms, regardless of baseline serostatus (5 percent vs 6 percent [seropositive] and 4.9 percent vs 5.7 percent [seronegative]).

“No serious AEs were considered related to the investigational product or study procedures for either group,” the researchers said.

The TAK-003 arm had low rates of dengue fever and dengue haemorrhagic fever, be it among those who were seropositive (0.4 percent and <0.1 percent) or seronegative (0.5 percent and 0.2 percent). A similar pattern of dengue fever and dengue haemorrhagic fever incidence was seen in the placebo arm (1.3 percent and 0.2 percent [seropositive] and 1.2 percent and 0.1 percent [seronegative]).

A challenge for high-risk, underserved regions

In this trial, 20,099 participants (mean age 9.6 years, 50 percent male) were randomized 2:1 to receive two SC 0.5-mL doses of TAK-003 or placebo 3 months apart. Ninety-one percent completed ~4.5 years of follow-up after the second vaccine. About a quarter (28 percent) of participants had no previous DENV exposure at baseline. Enrolment was balanced between Asia (45 percent) and Latin America (55 percent).

At ~57 months after the first dose, febrile illnesses were reported in 17,978 patients in the TAK-003 arm and 9,698 in the placebo arm. Of these illnesses, virologically confirmed dengue was detected in 2.5 percent and 5.8 percent, respectively.

During the last 18 months, there were fewer cases of virologically confirmed dengue in the TAK-003 (n=55/447) and placebo arms (n=57/560). “All four serotypes were detected in Asia, whereas most virologically confirmed dengue cases in Latin America were caused by DENV-1 and DENV-2,” the researchers noted.

The dengue disease burden has already dropped in 2020 and 2021, but it took a different turn when an upsurge was observed in 2022. [Lancet Infect Dis 2022;22:657-667; https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON448] “Even with reductions in disease burden in many countries, the diagnosis and treatment of dengue place immense pressure on healthcare services in underserved regions and those already overwhelmed by COVID-19, particularly in urban high-risk areas for both diseases,” said the researchers.

“[As the] global burden of dengue is high and growing … [t]he long-term efficacy and safety data presented in this report demonstrates potential for TAK-003 to help combat the risk of dengue disease posed to those living in, or travelling to, dengue-endemic areas,” the researchers concluded.

TAK-003 has gained approval for use in individuals with and without prior dengue infection in the EU, UK, and other dengue-endemic countries. [https://www.ema.europa.eu/en/documents/product-information/qdenga-epar-product-information_en.pdf; https://www.pom.go.id/siaran-pers/persetujuan-izin-edar-vaksin-dengue-qdenga-untuk-usia-6-45-tahun]