ATHENS, September 5, 2007 – In a new analysis of data from the European subset of the large clinical study REST (Rotavirus Efficacy and Safety Trial), the five-type rotavirus vaccine RotaTeq® demonstrated 100%a clinical efficacy against severe rotavirus disease for the first rotavirus season after vaccinationb. The efficacy remained high through two rotavirus seasons of follow up, preventing 98%c of severe rotavirus cases.1 This new sub-analysis was presented last week at the 25th International Congress of Paediatrics in Athens.
Results across four Phase II/Phase III clinical trials in different regions of the world, including the complete REST study with nearly 70,000 infants enrolled worldwide, already supported the consistently high clinical efficacy of 98% to 100% of RotaTeq® in the prevention of severe rotavirus disease due to virus types directly targeted by RotaTeq®1.
In this REST sub-analysis, assessing the response of more than 30,000 European infants, RotaTeq® has also been shown to reduce the number of hospitalisations and accident and emergency department visits by 95%d and to lower the number of GP surgery visits by 87%,e due to serotypes G1 to G41 up to two years post vaccination in Europe.
“These data all together demonstrate that there is highly consistent and lasting protection across multiple studies of RotaTeq® and illustrates the public health benefit of this vaccine” said Timo Vesikari, Professor of Virology and Head of the Division of Paediatric Infectious Diseases at the University of Tampere, Finland. “Moreover, as rotavirus infection peaks between 6 and 24 months of age, it is important to vaccinate infants before 6 months of age to help ensure sufficiently long protection".
RotaTeq® is the only five-type rotavirus vaccine offering protection against the five rotavirus types that cause more than 98% of rotavirus diseases in Europe (G1, G2, G3, G4 and G9).2,3,4 In the European Union (25 member states), RotaTeq® was approved in June 2006; it is already available in 11 countries and being launched in several others.
Rotavirus is the most common cause of severe dehydrating diarrhoea in children worldwide5 and virtually all children will be infected with rotavirus within the first five years of life.6, 7 Rotavirus disease is a leading cause of infant hospitalisation due to gastroenteritis in Europe.8
Notes to editors
Rotavirus Gastroenteritis: an underestimated, unpredictable and unavoidable disease
In the European Union (25 member states), it is estimated that each year, 87,000 children less than 5 years of age are hospitalised due to rotavirus gastroenteritis and over 700,000 visit the doctor. It has been estimated that 1 child dies every week because of rotavirus infection.9
The typical symptoms of rotavirus disease are watery diarrhoea, vomiting, fever and abdominal pain. The severity ranges from asymptomatic forms (most of the cases) to severe forms with a dramatic loss of body fluid (dehydration) that can be fatal.10
Rehydration is the key treatment in the UK and should be administered as soon as possible in the form of oral re-hydration fluids which can be purchased from retail pharmacies. There are no risk factors for developing a severe case of rotavirus gastroenteritis. Overnight, seemingly mild forms of the disease can become life-threatening 10, 11, 12 and require hospitalisation for intravenous re-hydration.
As rotavirus is highly contagious and relatively resistant to its environment, 10, 13, 14 there has been no real way to prevent rotavirus infection in children until now. Vaccination is recognised as a measure in helping to prevent infections, and this may have a significant impact on the incidence of severe rotavirus gastroenteritis.6, 11
More about RotaTeq®
In clinical trials, RotaTeq® has shown to prevent 98% to 100% of severe rotavirus gastroenteritis due to the rotavirus types G1, G2, G3 and G4 in several clinical studies.1, 4,15,16 The vaccine also reduced related hospitalisation and accident and emergency department visits due to rotavirus types G1, G2, G3 & G4 by 94.5%f and hospitalisation and accident and emergency department visits due to the rotavirus type G9 by 100%.g 1,4 Currently, RotaTeq® has already demonstrated protection up to two years after completion of vaccination, thus covering the peak age for rotavirus infections in infants.1,4
The tolerability and efficacy of RotaTeq® have been evaluated in a very large scale clinical program, including the largest rotavirus vaccination trial ever conducted, the Rotavirus Efficacy and Safety Trial (REST), which enrolled more than 70,000 infants worldwide with 43% (31,000) coming from Europe.17 In the REST study, no difference has been shown between RotaTeq® and placebo for the most common adverse events, which were vomiting, diarrhoea and fever. No difference between RotaTeq® and placebo has been shown concerning serious adverse events, such as intussusception.4
RotaTeq® (rotavirus vaccine, live, oral) is an oral, fully liquid and ready-to-use vaccine with three doses, indicated in the European Union for the active immunisation of infants from the age of six weeks for prevention of gastroenteritis due to rotavirus infection.18
RotaTeq® has been approved in more than 60 countries around the world. In the European Union, it is available in Austria, Belgium, Denmark, Finland, France, Germany, Greece, Italy, Luxembourg, Portugal and Spain.
REST Study details
Severe rotavirus disease: Rotavirus disease is defined as vomiting and/or at least three watery stools in 24-hours and detection of RV antigen in a stool by ELISA. Serotypes were identified using RT-PCR (Clark's severity score >16/2419.)
REST was a double-blind, placebo-controlled phase III clinical study that enrolled more than 70,000 infants worldwide with 43% (31,000) of these infants coming from Europe20. RotaTeq® was administered four to ten weeks apart, with the first dose at age six to twelve weeks.
The protective efficacy of RotaTeq® was evaluated in two ways:
1.) In 5,673 enrolled infants (2,834 in the vaccine group) protective efficacy was measured as a reduction in the incidence of rotavirus gastroenteritis caused by vaccine serotypes (G1-G4) that occurred at least 14 days after the third dose of vaccine through the first full rotavirus season after vaccination. In this cohort RotaTeq® prevented 74%h of PRG (Paediatric Rotavirus Gastroenteritis) of any severity.
2.) In 68,038 enrolled infants (34,035 in the vaccine group) protective efficacy was measured as a reduction in the rate of hospitalisations and emergency department visits for rotavirus gastroenteritis from 14 days for up to a maximum of two years after the third dose.
Intussusception: During the combined 42-day periods following each dose, there were 6 cases of intussusception in 34,837 recipients of RotaTeq® compared with 5 cases in 34,788 placebo recipientsi. There was no causal relation of intussusception and vaccine.
Phase II/Phase III Studies
1. A double-blind, placebo-controlled clinical trial conducted at four sites in Finland between June 1998 and June 2001. RotaTeq® was administered to healthy infants of 2-8 months of age. A total of 499 infants were analysed for rotavirus gastroenteritis (G1-G4), 237 RotaTeq® and 262 placebo15.
2. A double-blind, placebo-controlled phase III clinical trial conducted in 27 sites in the US and 3 sites in Finland from September 2002 to June 2004. RotaTeq® was administered to healthy infants of ~6-12 weeks of age. A total of 1112 infants were analysed for efficacy against severe rotavirus gastroenteritis (G1-G4)16.
About Sanofi Pasteur MSD
Sanofi Pasteur MSD is a joint venture between sanofi pasteur, the vaccine division of sanofi-aventis, and Merck & Co. Inc.. Combining innovation and expertise, Sanofi Pasteur MSD is the only company in Europe dedicated exclusively to vaccines. Sanofi Pasteur MSD is able to draw on the research expertise of sanofi pasteur and Merck & Co. Inc., together with their teams throughout the world, to focus on the development of new vaccines for Europe, which aim to extend protection to other diseases and perfect existing vaccines in order to improve the acceptability, efficacy and tolerability of vaccination.
a 95 % Confidence Interval: 91 to 100%
b Based on data available for vaccinated infants evaluated in Finland as part of the European subgroup ; vaccine n=1344 placebo n=1342
c 95 % Confidence Interval : 90 to 100%
d 95 % Confidence Interval: 91 to 97%
e 95 % Confidence Interval: 68 to 95%
f 95 % Confidence Interval: 91.2 to 96.6%
g 95 % Confidence Interval: 67.4 to 100%
h 95 % Confidence Interval: 66.8 to 79.9%
I 95 % Confidence Interval for the risk: 0.4, 6.4
1 Vesikari T et al., Efficacy of RotaTeq® to reduce any severity and severe rotavirus disease in Europe. Poster presentation ICP 2007.
2 Santos N and Hoshino Y. Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 2005;15:29-56.
3 Van Damme P et al., Distribution of Rotavirus Genotypes in Europe, 2004-2005: The REVEAL Study, J. Infect. Dis. 2007, 195[Suppl 1], S17-S25.
4 Vesikari T et al. Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine. N Engl J Med 2006; 354(1):23-33.
5 Centers for Disease Control and Prevention. Rotavirus. http://www.cdc.gov/rotavirus/ (last visit 16 April 2007).
6 Parashar UD. et al. Global illness and deaths caused by rotavirus disease in children. Emerg Inf Dis 2003;9:565-572
7 Clark HF et al. Rotavirus Vaccines. In: Plotkin SA, Orenstein WA eds. Vaccines 4th Ed. Philadelphia: Saunders; 2004. p. 1327-1345.
8 Van Damme P et al., Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAl study. J Infect Dis 2007, 195 [suppl1]: S4-16.
9 Soriano-Gabarro M et al. Burden of rotavirus disease in European Union Countries. Pediatr Infect Dis J 2006;25:S7-S11.
10 Raebel MA, Ou BS. Rotavirus disease and its prevention in infants and children. Pharmacotherapy 1999;19(11):1279-1295.
11 Clark HF and Offit PA. Vaccines for rotavirus gastroenteritis universally needed for infants. Ped Ann 2004; 33(8). 537-543.
12 Matson D.O. In: Long SS Ed. Principles and Practice of Paediatric Infectious Diseases. New York: Churchill Livingstone 2003. 1105-1108.
13 Fischer TK, Bresee JS, Glass RI. Rotavirus vaccines and the prevention of hospital acquired diarrhea in children. Vaccine 2004;22:49-54.
14 Dennehy PH. Transmission of rotavirus and other enteric pathogens in the home. Pediatr infect Dis J 2000; 19[Suppl10]: S103-5.
15 Vesikari T et al. Effects of the potency and composition of the multivalents human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants. Vaccine 2006; 24: 4821-4829.
16 Block SL et al. Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine at the end of shelf life. Pediatrics 2007;119:11-18.
17 Vesikari T et al. Clinical Trials of rotavirus vaccines in Europe. Pediatr Infect dis J 2006;25(1):S42-S47.
18 RotaTeq SmPC. 2006
19 Clark HF et al. Protective effect of WC3 vaccine against rotavirus diarrhea in infants during a predominantly serotype 1 rotavirus
season. J Infect Dis 1988;158(3):570-587.
20 Vesikari T et al. Clinical Trials of rotavirus vaccines in Europe. Pediatr Infect dis J 2006;25(1):S42-S47.
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Code: UK 10902 Date of preparation: 040907
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