TAK-003 Dengue Vaccine Shows Promise in Phase 3 Trial in Children and Adolescents

Takeda Pharmaceuticals’ dengue vaccine candidate exhibited protection against virologically-confirmed dengue in children and adolescents aged 4 to 16 years in phase 3 research, according to the primary endpoint analysis.

The vaccine candidate, TAK-003, is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all 4 serotypes, according to the company.

The Tetravalent Immunization against Dengue Efficacy Study (TIDES) is an ongoing double-blind, randomized, placebo-controlled study that is evaluating the safety and efficacy of 2 doses of TAK-003. Primary efficacy data from part 1 of the trial were published in the New England Journal of Medicine.

The study enrolled healthy children and adolescents between the ages of 4 and 16 years who lived in areas of Asia and Latin America where dengue is endemic. At enrollment, the participants were randomly assigned in a 2:1 ratio to receive 2 doses of the vaccine candidate or placebo 3 months apart.

The primary end point was overall efficacy of the vaccine to prevent virologically confirmed dengue caused by any dengue virus serotypes.

A total of 20,071 participants were given at least 1 dose of vaccine or placebo, 19,021 (94.8%) received both injections and were included in the per-protocol analysis.

The overall vaccine efficacy among participants who received at least 1 dose was 80.9% (95% confidence interval [CI], 75.2 to 85.3). There were 78 cases of dengue per 13,380 [0.5 per 100 person-years] in the vaccine group compared to 199 cases per 6687 [2.5 per 100 person-years] in the placebo group.

In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3). There were 61 cases of dengue in the vaccine group versus 149 cases in the placebo group. The efficacy against dengue leading to hospitalization was 95.4% (95% CI, 88.4 to 98.2), with 5 hospitalizations in the vaccine group and 53 hospitalizations in the placebo group.

“Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group),” the authors wrote, elaborating that efficacy trends varied according to serotype.

The incidence of serious adverse events was similar between groups (3.1% in the vaccine group compared to 3.8% in the placebo group).

The phase 3 TIDES trial will continue to assess safety and efficacy in study subjects for a total of 4.5 years.

The primary endpoint analysis evaluated vaccine efficacy and safety through 15 months after the first dose. The second part of the study continued for an additional 6 months to complete the assessment of the secondary endpoints of vaccine efficacy by serotype, baseline serostatus and severity. The final part of the study will evaluate efficacy and long-term safety by following participants for an additional 2 years.

“The results of this first analysis are very encouraging, indicating that the vaccine could potentially provide important public health benefits against dengue fever and hospitalization,” said Humberto Reynales, MD, PhD, a lead author of the New England Journal of Medicine paper said in Takeda’s statement. “It will be important to further analyze the trial results over time in order to assess the long-term efficacy and safety of the vaccine. If longer follow-up data confirm this initial observation, we are looking at a significant step forward in the global fight against dengue.”