Results of an ongoing phase 3 trial of Takeda’s tetravalent dengue vaccine candidate, known as TAK-003, suggest that the vaccine is effective in children and adolescents aged 4 to 16 years.
The findings, which were presented previously at the annual meeting of the American Society of Tropical Medicine and Hygiene, have now been published in The New England Journal of Medicine.
“It is important that there are multiple options to fight dengue, as it is the fastest spreading mosquito-borne disease and one of the top 10 threats to global health, according to WHO,” Derek Wallace, MBBS, vice president and global program lead in dengue for Takeda, told Infectious Diseases in Children. “In the absences of a specific treatment, prevention of dengue becomes very important.”
Wallace stressed that vector control and personal measures to reduce exposure to mosquitos have not been sufficient in preventing disease.
One other tetravalent dengue vaccine, known as Dengvaxia (CYD-TDV, Sanofi Pasteur), has been used in children in Asia and Latin America. However, Wallace and colleagues wrote that the vaccine increased the risk for severe dengue and dengue-related hospitalizations in children who had never been infected with the virus. Because of the increased risk for severe outcomes, Dengvaxia is only recommended for those with confirmed previous dengue virus infection.
“This leaves a significant unmet need for a vaccine that is safe and protects those at risk for dengue regardless of previous dengue exposure,” Wallace said.
For the trial, the researchers administered TAK-003 to healthy children and adolescents residing in endemic areas in Asia and Latin America. Participants received either two doses of the vaccine or placebo, with 3 months between each dose.
More than 20,000 children and adolescents were administered at least one dose of the vaccine or placebo, and nearly all (94.8%) received both doses. Wallace and colleagues wrote that one dose of the vaccine was 80.9% effective (95% CI, 75.2%-85.3%). Compared with placebo, the rate of infection was lower among children who received one dose of the vaccine (0.5 vs. 2.5 cases per 100 person-years).
Wallace said that the efficacy between the first and second dose of TAK-003 was “important and unexpected.”
“While this may have relevance for travelers and in outbreak settings, long-term safety and efficacy is assessed after two doses,” he said. “We therefore intend to file with a two dose regimen.”
Two doses of the vaccine were 80.2% (95% CI, 73.3%-85.3%) effective at preventing infection . The researchers identified fewer cases of virologically confirmed dengue virus infection among those who received two doses of the vaccine compared with placebo (61 vs. 149), and there was a 95.4% (95% CI, 88.4%-98.2%) reduction in hospitalizations due to dengue among recipients of TAK-003.
That last finding has “significant potential relevance,” according to Wallace.
“Dengue is an epidemic disease and creates huge pressure on public health infrastructure,” he explained. “There are an estimated 500,000 hospitalizations due to dengue each year. A reduction in hospitalization is therefore relevant both to the individual and to the public health systems in dengue-endemic areas. We are especially encouraged to note that the reduction in risk of hospitalization was observed in both seropositive and seronegative individuals.”
Before vaccination, 27.7% of participants who received both doses of TAK-003 were seronegative at baseline. Wallace and colleagues wrote that the vaccine demonstrated 74.9% efficacy in these children and adolescents (95% CI, 57%-85.4%), with 20 cases of virologically confirmed dengue virus infection occurring among those who received the vaccine and 39 cases among those who received placebo.
The researchers identified similar rates of adverse events among those who received the vaccine (3.1%) and those who received placebo (3.8%).
Wallace said the next steps in the trial include an analysis of an additional 6 months of data to determine the vaccine’s efficacy by serotype, baseline serostatus and severity of disease. He said these data will be presented at the upcoming American Society of Tropical Medicine and Hygiene annual meeting. A third analysis will examine the vaccine’s efficacy and long-term safety after an additional 3 years.
“We continue to collaborate with governments, nongovernmental organizations, policy organizations and dengue experts to ensure they have early and ongoing access to our data,” Wallace said. “These are the individuals and groups that are most important in defining how the vaccine candidate could potentially best be used. We will focus on filing in dengue-endemic countries where there is the greatest need in parallel with filings in nonendemic countries. The planned dossier will include safety and efficacy data from our trial and supporting data from our other phase 3 studies.” – by Katherine Bortz
Disclosures: Wallace is an employee of Takeda. Please see the study for all other authors’ relevant financial disclosures.