Presenter of 1 Presentation
OVERVIEW OF TAKEDA’S TETRAVALENT DENGUE VACCINE CANDIDATE CLINICAL DEVELOPMENT TO DATE
Abstract
Background
Dengue is a mosquito-borne viral disease endemic in at least 128 countries and a potential threat for travelers to these countries.
Aims
Takeda’s vaccine candidate (TAK-003) is a recombinant tetravalent dengue vaccine based on a DENV-2 backbone. The clinical development program includes an ongoing long-term Phase III efficacy clinical trial in eight dengue endemic countries evaluating long-term efficacy, safety, and immunogenicity which currently has 3 years data available.
Methods
Overall, 18 clinical trials have included 28,175 participants aged 1.5-60 years in 13 endemic and non-endemic countries. In the Phase III efficacy study, healthy 4–16 year-olds (n=20,099) were randomized 2:1 to receive two doses of TAK-003 or placebo three months apart, and are under active febrile illness surveillance to detect symptomatic dengue.
Results
Safety and immunogenicity data from Phase I/II studies established the final formulation and dosing schedule. In the pivotal Phase III efficacy study the cumulative vaccine efficacy from first dose through three years after the second dose was 62.0% (95% Confidence Interval: 56.6–66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8–88.4) against hospitalized VCD for safety set. Efficacy varied by serotype and some decline in efficacy was noted in a year-to-year comparison but remained robust against hospitalized VCD. Rates of serious adverse events were similar between the vaccine and placebo groups. No important safety risk was identified.
Conclusions
TAK-003 was well tolerated and protected against symptomatic dengue over three years after vaccination in both dengue-naïve and pre-exposed children in dengue endemic countries with no evidence of disease enhancement to date.