Dengue Vaccine Initiative Statement on Results of Studies on the Efficacy and Long-Term Safety of Sanofi Pasteur’s Dengue Vaccine Candidate in Dengue-Endemic Regions
WASHINGTON DC – JULY 28, 2015—A study titled “Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease” (Hadinegoro et al.), published yesterday in The New England Journal of Medicine, assesses vaccine efficacy and interim long-term safety results of Sanofi Pasteur’s dengue vaccine candidate, CYD-TDV, across three clinical trials in dengue-endemic countries within Asia-Pacific and Latin America. This analysis marks a significant scientific milestone in Sanofi Pasteur’s efforts to develop a dengue vaccine.
Analyses of pooled data from the two Phase 3 trials (CYD14 in Asia-Pacific and CYD15 in Latin America) showed a reduction in dengue disease during the first 25 months of the study among children and adolescents 2-16 years of age who received CYD-TDV, consistent with previously published results from each trial. The pooled data allowed for greater post-hoc analysis of age effects. Among individuals aged 9 years and older, efficacy was substantially higher at 65.6% than in younger children. Children aged 9 and older who had evidence of prior dengue virus infection (i.e., were seropositive) had an efficacy of 81.9%; seronegative individuals in this age group had significant efficacy of 52.5%. Serotype-specific efficacy was also significant in the older age group, ranging from 47.1% against serotype 2 to 83.2% against serotype 4. Among children younger than 9 years of age, efficacy was lower at 44.6% with 70.1% efficacy in seropositive and 14.4% in seronegative children. Efficacy against severe dengue and hospitalization was 93.2% and 80.8%, respectively, in individuals aged 9 years or older; and 44.5% and 56.1%, respectively, in children younger than 9 years.
Long-term safety follow up from the third year of the Phase 3 trials and from the third and fourth years of a Phase 2b long-term follow up study (CYD23/57) conducted in Thailand demonstrated reduction in dengue hospitalizations among individuals 9-16 years of age for up to two years after completion of the three-dose vaccine regimen. The pooled relative risk of hospitalization among individuals aged 9 years or older was 0.50, demonstrating significantly decreased risk in vaccine recipients. However, this risk reduction was not observed among vaccinated children under 9 years old. The pooled relative risk of dengue hospitalization in this younger vaccinated group was 1.58 during the third year, suggesting a trend to increased risk. Among the very young children, this increased risk became more apparent. The relative risk of hospitalization in 2-5 year old vaccinated children during the third year of CYD14 was 7.45 and in 4-5 year old vaccinated children in the third year of CYD 23/57 was 2.44.
The Dengue Vaccine Initiative welcomes the demonstrated vaccine efficacy across age groups and geographic regions. In particular, the Initiative is encouraged by the overall level of protection and prevention of severe dengue and hospitalizations among individuals 9 years of age or older, along with the significant reduction in dengue cases among both seropositive and seronegative individuals within this age group without apparent safety issues. However, DVI considers further evaluation in the population at large, especially in children younger than 9 years of age, to be crucial to better understand the effects of this vaccine, as well as to clarify the duration of protection. Of particular importance will be to understand why there appeared to be an increased risk of hospitalization among the very young during the third year, and whether this risk continues into subsequent years. Safety signals clearly exist for persons aged less than 5, but the mechanism remains unclear. DVI looks forward to further information from the additional years of long-term safety follow up from these three ongoing trials. Additionally, the Initiative continues to be highly interested in whether fewer number of doses could provide similar levels of protection by this candidate, as well as its forecasted price if licensed.
About the Study
The results are based on CYD14, a Phase 3 trial involving 10,275 individuals aged 2–14 years from Indonesia, Malaysia, the Philippines, Thailand and Vietnam; CYD15, a Phase 3 trial of 20,869 individuals aged 9–16 years from Brazil, Colombia, Honduras, Mexico and Puerto Rico; and CYD23/57, a Phase 2b trial and long-term safety study of 3,203 children aged 4-11 years (at time of vaccination) from Thailand.
Dengue is the most common vector-borne viral disease. It causes an estimated 390 million infections a year in over 120 countries, threatening the health of 40% of the global population. Urgent preventive intervention is needed, however, no licensed dengue vaccine is currently available. A safe, effective and affordable vaccine would represent a major advancement for the control of dengue.
- World Health Organization Q&A on efficacy and longer-term safety of CYD-TDV
- More about the burden of dengue here and dengue vaccines here.
DVI is an international consortium that specializes in epidemiology and other research, health economics, policy and advocacy to equip countries with objective information and scientific evidence to fight dengue fever. The Initiative is supported in part by the Bill & Melinda Gates Foundation.
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