Dengue vaccine efficacious in phase 3 trial
Sanofi Pasteur’s investigational quadrivalent dengue vaccine demonstrated an overall efficacy of 56.5% and led to an 88.5% reduction of severe disease among children, according to the results of a phase 3 trial published in The Lancet.
“The results of this first phase 3 study show the potential of the vaccine to have a significant impact on public health,” study researcher Maria Rosario Capeding, MD, of the Research Institute for Tropical Medicine in the Philippines, said in a press release. “The threat of severe dengue disease creates fear in the community. The vaccine’s impact on preventing dengue hemorrhagic fever is noteworthy. A vaccine that is able to avoid the personal suffering and reduce this significant health burden would change the lives of millions.”
The randomized clinical trial included 10,275 children aged 2 to 14 years in five countries across the Asian-Pacific region, including Indonesia, Malaysia, Thailand, Vietnam and the Philippines. Children received three injections of a recombinant, live-attenuated, quadrivalent dengue vaccine (CYD-TDV) or placebo at 0, 6 and 12 months. Participants were followed up for 25 months.
Results indicated that 250 cases of virologically confirmed dengue infection took place more than 28 days after the third injection — 117 (47%) children who received the vaccine and 133 (53%) in the control group. The vaccine reduced up to 56.5% (95% CI, 43.8-66.4) of cases, and its efficacy was higher in children with pre-existing dengue neutralizing antibodies.
Secondary analyses suggested that all four dengue serotypes contributed to the vaccine’s overall efficacy.
After three injections, vaccine efficacy against hemorrhagic fever was 88.5% (95% CI, 58.2-97.9). The vaccine also reduced hospital admissions by 67.2% (95% CI, 50.3-78.6).
The safety profile of CYD-TDV was favorable, according to the researchers. A total of 647 serious adverse events were recorded; 402 (62%) in the vaccine group and 245 (38%) in the control group. Serious adverse events were consistent with medical disorders typical for this age group and resulted primarily from infections and injuries, the researchers said.
The study revealed a significantly higher burden of disease than previously expected — up to three times higher, with an estimated one in 20 children in the control group affected by dengue each year.
“This trial was successfully done over more than 2 years in diverse dengue-endemic areas in Asia, a region that accounts for 70% of the global dengue burden,” the researchers wrote. “In this setting, we recorded promising results pointing to a substantial effect on severe disease manifestations. The safety and efficacy profile described here suggests that the CYD-TDV vaccine candidate, when given as three injections at months 0, 6, and 12 to 2-14 year-olds, has the potential to provide an important public health benefit in dengue-endemic countries.”
Disclosure: The study was funded by Sanofi Pasteur.