Alain Bouckenooghe

SanofPasteur,N°6 Raffes Quay 16-00,048580,Singapore

Clinical development update:1st dengue vaccine candidate

Alain Bouckenooghe*

SanofPasteur,N°6 Raffes Quay 16-00,048580,Singapore

A R T I C L E I N F O

Article history:

Available online 28 October 2015

Dengue vaccine

Candidate tetravalent dengue

vaccine

A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in the Asia-Pacifc and Latin American countries.We report the results of long-term follow-up interim analyses and integrated effcacy analyses.

We are assessing the incidence of hospitalization for virologically confrmed dengues a surrogate safety end point during follow-up in years 3–6 of two phase 3 trials,CYD14 and CYD15, and a phase 2b trial,CYD23/57.We estimated vaccine effcacy using pooled data from the frst 25 months of CYD14 and CYD15.

Follow-up data were available for 10,165 of 10,275 participants(99%)in CYD14 and19,898 of 20,869 participants(95%) in CYD15.Data were available for 3203 of the 4002 participants(80%)in the CYD23 trial included in CYD57.During year 3 in the CYD14,CYD15,and CYD57 trials combined,hospitalization for virologically confrmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group.Pooled relative risks of hospitalization for dengue were 0.84(95%confdence interval[CI], 0.56–1.24)among all participants,1.58(95%CI,0.83–3.02)among those under the age of 9 years,and 0.50(95%CI,0.29–0.86) among those 9 years of age or older.During year 3,hospitalization for severe dengue,as defned by the independent data monitoring committee criteria,occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group.Pooled rates of effcacy for symptomatic dengue during the frst 25 months were 60.3%(95%CI,55.7–64.5)for all participants,65.6%(95%CI,60.7–69.9)for those 9 years of age or older,and 44.6%(95%CI,31.6–55.0)for those younger than 9 years of age.

Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term followup,the risk among children 2–16 years of age was lower in the vaccine group than in the control group.

R E F E R E N C E S

[1]Hadinegoro SR,Arredondo-García JL,Capeding MR,et al. Effcacy and long-term safety of a dengue vaccine in regions of endemic disease.N Engl J Med 2015;27.

[2]Capeding MR,Tran NH,Rezeki SS,et al.Clinical effcacy and safety of a novel tetravalent dengue vaccine in healthy children aged 2 to 14 years in Asia:a phase III randomised observer-masked,placebo-controlled trial.Lancet 2014;370:1–8.

[3]Villar L,Dayan GH,Arredondo-García JL,et al.Effcacy of a tetravalent dengue vaccine in children in Latin America.N Engl J Med 2015;372:113–123.

*E-mail address:alain.bouckenooghe@sanofpasteur.com.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.014

1818-0876/?2016 The Author.Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).