Towards Dengue Vaccine Introduction:! Report of the Asia-Pacific Dengue Prevention Board Meeting

Transcription

1 Towards Dengue Vaccine Introduction:! Report of the Asia-Pacific Dengue Prevention Board Meeting Sri Rezeki S Hadinegoro Department of Child Health Medical Faculty University of Indonesia

2 Lay out Introduction Global dengue burden WHO dengue control strategies Dengue vaccine introduction APDPB report Conclusion

3 ! Global dengue burden! WHO dengue control strategies

4 Dengue infection is a major public health burden Distribu(on of dengue in Asia, Oceania, Africa & Middle East Incidence has increased 30 fold over the last 50 years. There are more than 100 endemic countries. There are 2.5 billion people living in endemic regions. The spread of dengue parallels the expanding range of the mosquito vector. Tomashek KM, Margolis HS. CDC Dengue sheet. CDC website:

5 Average annual number dengue cases reported! from most highly endemic countries Ten countries with the highest burden reported to WHO, Brazil Indonesia, Vietnam, Mexico, Venezuela Thailand, Philippines, Columbia, Malaysia, Honduras WHO Global Strategy for Dengue Preven3on and Control Geneva: World Health Organiza(on.

6 VACCINATION IS ONE OF THE PILLARS OF THE WHO STRATEGY TOWARDS EFFECTIVELY FIGHTING DENGUE 1 WHO OBJECTIVES Reduce mortality by 50% by 2020* Reduce morbidity by 25% by 2020* TECHNICAL ELEMENTS Es2mate true burden of disease by 2015 Diagnosis and case management Integrated surveillance and outbreak preparedness Sustainable vector control vaccine implementa(on 2 Basic opera(onal and implementa(onal research Baseline data in year of 2010 *The baseline year is WHO=World Health Organiza(on. 1. WHO, 2012, Global Strategy for Dengue Preven(on and Control. 2. Summary of the April 2016 mee(ng of the Strategic Advisory Group of Experts on immuniza(on (SAGE).

7 Introduc(on of New Vaccine IR, CFR, age, PH impact Burden of diseases Global concern SAGE, WHO Clinical trial data Vaccine safety & efficacy Vaccine availability Registration to Local FDA Cost Na(onal Health System Support to Ministry of Health policy WHO SEARO, 2010

8 Dengue vaccine introduction (CYD-TDV)

9 TWO PHASE III LARGE-SCALE RANDOMIZED EFFICACY STUDIES AND ONE PHASE IIb EFFICACY STUDY OF THE CANDIDATE DENGUE VACCINE INCLUDED >35,000 PARTICIPANTS IN ENDEMIC COUNTRIES 2009: first proof of concept phase IIb efficacy study; results published September : 2 large scale efficacy studies in Asia Pacific and La(n America; results published in ,3 Phase IIb Efficacy Asia Pacific (CYD23/57*) Proof of concept study 1,4 Country: Thailand Age group: 4 11 years Sample size: 4,002 Long term follow up: 5 years postdose 3 Year of comple2on: 2016 Phase III Efficacy Asia Pacific (CYD14) 3 Countries: Thailand, Indonesia, Malaysia, Vietnam, Philippines Age group: 2 14 years Sample size: 10,275 Long term follow up: 5 years postdose 3 Year of comple2on: 2017 *CYD57 is the long term follow up of CYD Sabchareon, 2012, Lancet. 2. Villar, 2015, N Engl J Med. 3. Capeding, 2014, Lancet. Phase III Efficacy La2n America (CYD15) 2 Countries: Colombia, Mexico, Honduras, Puerto Rico, Brazil Age group: 9 16 years Sample size: 20,869 Long term follow up: 5 years postdose 3 Year of comple2on: 2018

10 OBJECTIVE OF THE PUBLICATION: GLOBAL VIEW OF CLINICAL PROFILE OF SANOFI PASTEUR VACCINE CANDIDATE BASED ON EFFICACY AND LTFU INTERIM ANALYSES DATA CYD14 efficacy study in Asia years (N=10,275) CYD15 efficacy study in La2n America and the Caribbean years (N=20,869) hlp://linkinghub.elsevier.com/retrieve/pii/s hlp:// Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease 3 LTFU=long term follow up. 1. Capeding, 2014, Lancet. 2. Villar, 2015, N Engl J Med 3. Hadinegoro, 2015, N Engl J Med.

11 SUMMARY OF POOLED EFFICACY: EFFICACY WAS CONSISTENTLY DEMONSTRATED FOR THE CANDIDATE DENGUE VACCINE IN SUBJECTS AGED 9 16 YEARS IN THE 25-MONTH ACTIVE PHASE1 Pooled results (CYD14+CYD15; ITT) Any serotype DENV 1 DENV 2 DENV 3 DENV 4 VE (%) and 95% CI Severe dengue DHF (WHO) Hospitalized cases In dengue seroposi2ve subjects In dengue seronega2ve subjects DENV=dengue virus; DHF=dengue hemorrhagic fever; ITT=intent to treat; VE=vaccine efficacy; WHO=World Health Organiza(on Hadinegoro, 2015, N Engl J Med.

12 SAFETY OVERVIEW AFTER ANY DENGUE VACCINE OR PLACEBO DOSE SUBJECTS 9 60 YEARS OF AGE 1 INTEGRATED SAFETY ANALYSIS* Unsolicited non serious AE Placebo (n=1780) CYD vaccine (n=4615) Solicited systemic reac(on Solicited injec(on site reac(on Solicited AR Immediate unsolicited AR Percentage of subjects presen2ng with at least 1 reac2on or event *Integrated safety analysis pooling data from 13 studies that used the final formula(on and final vaccina(on schedule (CYD12, 13, 22, 24, 28, 30, 47, 23, 17, 32, 14, 15, 51). AE=adverse event; AR=adverse reac(on. 1. Chuenkitmongkol, 2015, JITMM.

13 SAGE Recommendation! April 2016 The Strategic Advisory Group of Experts on Immunization (SAGE) recommendations indicate that routine vaccination with CYD-TDV should be considered for children aged at least 9 years in highly endemic settings (dengue seroprevalence 70% but not less than 50%)

14 WHO Position Paper July 2016 The target age for routine dengue vaccination should be defined by each country based on an assessment of dengue endemicity and programmatic feasibility of targeting particular age groups.

15 Dengue age specific seroprevalence:! nearly all children infected by age 18 year Seroprevalence study (DNG26) in Indonesia n = 3,198, 1 18 year of age in 30 districts At 1 year old, >25% of children infected at least once, at 5 years old > 50% infected Dengue seroprevalence: 95% in the 18 years old children Ref. Ari Prayitno et al. Dengue seroprevalence and force of primary infection in urban dwelling Indonesian children: a nationally-representative study. Presented at ICID Hyderabad Feb 2016

16 Asia Pacific Dengue Prevention Board

17 Dengue Vaccine Initiative hosts two regional Dengue Prevention Boards Asia-Pacific Dengue Prevention Board (APDPB) 13 members from the region Public health & Vaccine policy Americas Dengue Prevention Board (AmDPB)

18 Asia-Pacific Dengue Prevention Board Convened mee(ngs each year to address issues related to dengue preven(on Disseminate information Make recommendations concerning best practices related to dengue control To advocate for dengue prevention through immunization

19 APDPB June 2016! Kuala Lumpur, Malaysia The meeting highlighted points for consideration in light of licensure of the first dengue vaccine In particular, the meeting sought answers to What are the specific priorities for countries to make decisions regarding the introduction? What specific factors do countries need to consider when making decisions about introduction?

20 Key Highlights (1) A comprehensive roadmap for vaccine introduction should be prepared by each country before any decisions are made about vaccine introduction Decision-making should be based on a clear understanding of available country-specific data about dengue endemicity A communication plan should be prepared beforehand to address specific questions Experiences and lessons learned among countries The private sector should be considered along with public sector.

21 Key Highlights (2) Plans for appropriate post-introduction studies of vaccine effectiveness and safety should be prepared beforehand Adequate surveillance systems to detect dengue cases should be in place both before and after possible vaccine introduction Vaccination registries (electronic or paper-based) should be established or improved. Adequacy of diagnostic assays should be addressed (e.g., molecular/antigen detection vs serological tests with potential cross-reactivity).

22 Tools required (1) Identification and modification (if appropriate) of existing WHO guidance documents relevant to dengue vaccine introduction Generic Principles and considerations for adding a vaccine to a national immunization program Considerations regarding consent in vaccinating children and adolescent between 9 and 17 years old School vaccination readiness assessment tool Vaccine safety guidance/reference documents/tools Immunization in practice: a practical guide for health staff Related (Human papillomavirus vaccine, HPV) Options for linking health interventions for adolescents with HPV vaccination

23 Tools required (2) Additional technical guidance documents for specific topics such as: methodologies to assess dengue seroprevalence and improve dengue surveillance development of vaccination registries Communication toolkits Country-specific technical support for assessing dengue endemicity (i.e. areas to target vaccination) establishing the economic case for dengue vaccine introduction developing vaccine registries (electronic or paper-based) clarifying the roles of various organizations

24 Integrated Management Strategies for Dengue in Latin America IMS-Dengue Working group within PAHO recognizes vaccination as a key tool to manage dengue

25 Conclusion APDPB recognized that the role of dengue vaccines in global public health has reached a critical juncture with the licensure of the first dengue vaccine It was discussed that many countries either introduced it (Philippines) or considering to introduce it Strategies outlined by APDPB shall facilitate decision making process for vaccine introduction in the region Effective and impactful introduction of this new tool will require experience sharing among countries and collaboration of all sectors

26 References Prevention Board reports WHO documents vaccine_intro_resources/nvi_guidelines/en/ consent_note/en/ school_assessment_tool/en/

27 Thank you