Based on the clinical profile in nine years of age and older, the dengue vaccine candidate has the potential to significantly reduce disease burden in endemic countries
Sanofi Pasteur’s new data analysis published in the New England Journal of Medicine (NEJM) provide a comprehensive picture of the potential public health impact of vaccinating endemic populations from pre-adolescence to adulthood against dengue. Not only is this the largest population at risk of dengue globally, but individuals nine years of age and older also represent a highly mobile group capable of spreading disease more broadly during outbreaks and also contributing substantially to the economic burden of dengue, for example in number of lost school and work days due to the disease.
The NEJM article reported results from a new pooled efficacy analysis of individuals nine years of age and older at vaccination from the two phase III studies of Sanofi Pasteur’s dengue vaccine. The new analysis documented that the vaccine protects two-thirds of these individuals (66 per cent) against dengue, providing even greater protection against two clinically-relevant manifestations of dengue, namely severe dengue (93 per cent) and prevention of hospitalisations due to dengue (80 per cent) that account for the greatest human and economic burden of dengue in endemic countries. In addition, the dengue vaccine candidate protected volunteers nine years of age and older who were previously exposed to dengue (82 per cent), as well as those who were naive to dengue (52.5 per cent) prior to vaccination.
The clinical development programme for the vaccine candidate includes studies with four-year, long-term follow-up phases, in line with WHO guidelines for dengue vaccine development. Results from first 25 months of the two phase III efficacy studies were published in 2014. Interim data from the third year of these studies and interim data from the third and fourth years of the phase II extension study in Thailand published in the new NEJM article confirm the continuing reduction of hospitalised dengue in the vaccinated population nine years of age and older.
The third-year interim data from the Asian phase III study identified the need for further long-term surveillance in children under nine years of age to assess the impact of the dengue vaccine candidate in these younger children.
“It is not unusual to require additional data on a new vaccine to determine its value in a specific age group, particularly young children, whose immune response to the vaccine and the disease itself 2/3 may differ significantly from that of older children and adults,” noted Tim Endy, from Upstate University Hospital, New York. “It is reassuring to have confirmation of the safe protection that this vaccine offers against dengue in the endemic pre-adolescent to adult population, particularly coupled with its consistent efficacy and safety profile reported last year from the PIII studies across diverse geographic regions, ethnic study populations and dengue epidemiology covered.”
Dr Maria Rosario Capeding from the Research Institute for Tropical Medicine in the Philippines, who is a lead author on the NEJM article, points out the potential public health benefit of having a first dengue vaccine available to protect individuals nine years of age and older. “This large, at-risk population includes the most dynamic members of the community who have the potential to spread disease widely and also contribute most to dengue’s heavy societal impact in terms of school absences and lost work productivity. Certainly, individuals nine years of age and older represent a compelling target group for an immunisation programme against dengue aimed at significantly reducing overall disease burden.”
Based on the totality of the safety and efficacy data for its dengue vaccine candidate, Sanofi Pasteur has decided to recommend a targeted age indication for the vaccine of nine years of age and older in endemic countries, where the combination of disease burden and the vaccine’s proven impact profile in this age group point to the greatest potential for reduction of dengue disease burden in these countries.