Takeda’s investigational dengue vaccine had an acceptable safety profile and induced a sustained antibody response after 18 months, according to interim phase 2 data.
The findings are from a planned 48-month trial analyzing the safety and immunogenicity of the vaccine candidate, TAK-003, in children living in dengue-endemic countries. They come on the heels of positive 6-month results that were published earlier this year.
The live-attenuated tetravalent vaccine is also being evaluated in a large phase 3 trial in eight dengue-endemic countries, with results expected in late 2018, Takeda said. It is given in two doses 3 months apart.
Dengue is the most common mosquito-borne virus in the world, but protecting against it has been a challenge. To be effective, a vaccine must prevent infection from all four dengue serotypes. Patients who become infected with one dengue serotype develop lifelong immunity to it, but they are at an increased risk for severe dengue if they are infected with one of the other three serotypes.
According to the new phase 2 results, TAK-003 is effective against all four dengue serotypes. The findings were published in The Lancet Infectious Diseases and presented at the American Society of Tropical Medicine and Hygiene annual meeting in Baltimore.
“These data are an important step in the development of our dengue vaccine candidate,” Derek Wallace, MBBS, head of Takeda’s global dengue program, said in a news release. “The reduced incidence of dengue in children and adolescents receiving TAK-003 is encouraging; however, data from our ongoing phase 3 efficacy trial, TIDES, are required to confirm these findings.”
Between Dec. 5, 2014, and Feb. 13, 2015, researchers randomly assigned 1,800 children aged 2 to 17 years into four groups at three sites in the Dominican Republic, Panama and the Philippines. The participants received either two doses of TAK-003 given 3 months apart (n = 201), one dose of the vaccine (n = 398), one dose followed by a booster dose 1 year later (n = 1,002), or placebo (n = 199).
According to the results, TAK-003 produced a durable immune response against all four dengue serotypes after 18 months in each of the vaccine groups regardless of vaccine schedule or previous exposure to the virus, with a relative risk for symptomatic dengue infection of 0.29 (95% CI, 0.13 to 0.72) compared with participants in the control group.
In the group that received a second dose after 3 months, the tetravalent seropositive rate was 86% after 6 months, compared with 69% among participants who received just one dose. In the group that received a booster dose at 12 months, 100% of participants who were seronegative at baseline were tetravalent seropositive 1 month later.
The researchers said the data “provide proof of concept for [TAK-003] and support the ongoing phase 3 efficacy assessment of two doses 3 months apart.” – by Gerard Gallagher
Sáez-Llorens X, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30632-1.
Tricou V, et al. Abstract 623. Presented at: American Society of Tropical Medicine and Hygiene conference; Nov. 5-9, 2017; Baltimore.
Disclosures: Wallace is head of Takeda’s global dengue program. Please see the study for all authors’ relevant financial disclosures.