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Gaps in knowledge of RSV
Louis Bont
ReSViNET: a Clinical RSV Research Network
• A global network of experts in RSV infections and clinical trial infrastructure
• Vision: combine expertise and leadership to decrease the global burden of RSV infection.
• Mission: perform high quality research to improve knowledge of RSV epidemiology, and to develop safe and effective therapeutic and preventive interventions.
1st ANNUAL RSV EXPERT MEETING JANUARY 2015
ORGANISED BY ReSViNET
2014
2015
Outline
1. Morbidity and Mortality
2. Timing of Vaccination
3. RSV, Wheeze and Asthma
RSV Epidemiology
• 34,000,000 Patients • 3,400,000 Hospitalizations • 253,000 Deaths
Pipeline RSV: Vaccines Overview
Can we prevent RSV mortality?
Schickli J Clin Invest 2015
McLellan, Science 2013
Corti Nature 2013
What is the peak age of RSV mortality?
rsvgold@umcutrecht.nl
Chu JID 2014 Bont PIDJ 2011
Prevention ICU admisions
rsvgold@umcutrecht.nl
• Multicenter ICU study (n=250)
• Healthy term
• Co- morbidity
• Prematurity
• Protection (hypothetical)
• 30 / 60 / 90 / 120 days
• Proportion prevented (%) 0
102030405060708090
100
30 60 90 120P
reve
nta
ble
Pts
(%
)
Duration of Protection (days)
Co-morbidity
0102030405060708090
100
30 60 90 120
Pre
ven
tab
le P
ts (
%)
Duration of Protection (days)
Healthy Term
Scheltema, in progress
Three Distinct Wheezing Phenotypes
RSV Infants wheeze Asthma
Stein Lancet 1999
Sigurs Thorax 2010
Bacharier JACI 2013
RSV and Asthma
RSV Bronchiolitis in Early Life (RBEL), n=206, < 13 months
Asthma < 7y 48%
Active asthma 35%
Bacharier, JACI 2013
Key Facts on Asthma
Unmet Need
Opportunity Risk
One of the major non-communicable diseases 235 million people currently suffer from asthma Common disease among children. Most asthma-related deaths occur in LMIC
Disability adjusted life years
Key Facts on Asthma
Unmet Need
Opportunity Risk
Costs in the United States “The annual direct health care cost of asthma is approximately $50.1 billion; indirect costs
(e.g. lost productivity) add another $5.9 billion, for a total of $56 billion dollars”
Prevention of Asthma
Unmet Need
Opportunity Risk
Prevention of Asthma Tobacco Smoke Exposure Respiratory Tract Infection Pollution
Chicken or Egg
Blanken NEJM 2013
Serial hypothesis Parallel hypothesis
Pre-existent healthy
Viral bronchiolitis
Recurrent wheeze
Pre-existent susceptibility
Viral
bronchiolitis
Recurrent
wheeze x
x
RSV and Wheeze
0
500
1000
1500
2000
2500
1 2 3 4 5 6 7 8 9 10 11 12
Cum
ula
tive w
heezin
g d
ays
Month follow-up
PalivizumabPlacebo
p<0.0001
Blanken NEJM 2013
Studying Long-term effects
1. Clinical Relevance (Quality of Life)
2. Societal Relevance (56 billion$)
3. Mechanism of Disease (parallel vs serial hypothesis)
4. Feasibility (small sample size)
Conclusions
1. Morbidity and Mortality
2. Timing of Vaccination
3. RSV, Asthma and Wheeze 0
500
1000
1500
2000
2500
1 2 3 4 5 6 7 8 9 10 11 12
Cu
mu
lative w
he
ezin
g d
ays
Month follow-up
PalivizumabPlacebo
Save The Date To Meet RSV Experts
DATE 19-21 JANUARY 2016 LOCATION THE NETHERLANDS WEBSITE www.resvinet.org
CONTACT ReSViNET Louis Bont (ReSViNET Chairman ) louis.bont@resvinet.org +31 (0) 88 75 75 114
Leyla Kragten-Tabatabaie (Network Manager)
leyla.kragten@resvinet.org +31 (0) 611 33 13 91
Cyrus Park (Manager Clinical Research & Development)
cyrus.park@juliusclinical.com +31 (0) 621 16 29 69
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