Sanofi announces results of first Phase III dengue vaccine in The Lancet
14 July 2014
Sanofi Pasteur, the vaccines division of Sanofi, today announced the publication of the detailed results of its first landmark phase III dengue vaccine efficacy study conducted in five countries in Asia, in The Lancet.
It said, results show overall efficacy against symptomatic dengue of 56.5%* in children aged 2 to 14 years old after a three-dose vaccination schedule. Importantly, analyses show an 88·5%* reduction of dengue haemorrhagic fever, the severe form of dengue, according to the WHO criteria (World Health Organisation. Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. 1997. http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/ (accessed 7 June 2014 2014)).
The study also showed a clinically important reduction in the risk of hospitalisation due to dengue by 67%* during the study. The favorable vaccine safety profile observed during the 25 month follow up of the phase III study in Asia is consistent with the safety profile documented in other studies (phase I, II, IIb).
(* 56.5% (95% CI: 43.8-66.4); 88·5% (95% CI 58·2 to 97·9); 67.2% (95% CI: 50.3 to 78.6).)
Dengue is a threat to nearly half the world's population, and is a pressing public health priority in many countries in Asia and Latin America where epidemics occur. The study confirmed the very high burden of disease by revealing that one in twenty children in the control group suffered from dengue each year, which was three-fold higher than initially expected. Each year, an estimated 500,000 people, including children, have severe dengue requiring hospitalization.This puts huge strain on hospitals and health care systems during outbreaks. (WHO Dengue and severe dengue fact sheet # 117 Updated March 2014 Available at http://www.who.int/mediacentre/factsheets/fs117/en/) .
"The results of this first phase III study show the potential of the vaccine to have a significant impact on public health," commented Dr. Maria Rosario Capeding, study principal investigator, Research Institute for Tropical Medicine, the Philippines. "The threat of severe dengue disease creates fear in the community. The vaccine's impact on preventing dengue haemorrhagic fever is noteworthy. A vaccine that is able to avoid the personal suffering and reduce this significant health burden would change the lives of millions."
Safety analyses (solicited reactions, unsolicited events and Serious Adverse Events SAEs) during the study showed similar reporting rates between the vaccine and control groups. SAEs were consistent with medical disorders in this age group and were mainly infections and injuries. Safety is continuously reviewed by an independent data monitoring committee. To date, 27,000 children, adolescents and adults have been vaccinated with three doses of the candidate dengue vaccine throughout the clinical studies.
"The high efficacy observed against severe dengue and the reduction of hospitalization by two thirds is an extremely important public health outcome. Furthermore this dengue vaccine continues to meet the highest safety expectations, which is very reassuring," commented Professor Duane Gubler, Professor and Founding Director of the Signature Research Program on Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore, and Chairman of the Partnership for Dengue Control.
"These pivotal phase III vaccine efficacy study results take us closer to our ambition to bring the first vaccine against dengue to the world," said John Shiver, Senior Vice President, R&D at Sanofi Pasteur. "After more than 20 years of commitment in collaboration with the scientific community, we are on course to make dengue the next vaccine-preventable disease. The public-health implications of a future dengue vaccine are significant and these findings are an important stride towards meeting the WHO's strategic goals of reducing dengue mortality by half and morbidity by at least 25% by 2020."
The four dengue virus serotypes have circulated during the study with a distribution representative of the epidemiology in Asia. The measured efficacy of the vaccine during the 25 months observation of the study is consistent across countries and appears to vary by dengue serotype (between 34.7% and 72.4%) and by age. The results of this first, large-scale efficacy study will be supplemented by results from a second, large-scale phase III study in Latin America and the Caribbean, including more than 20,000 children and adolescents aged 9 to 16 years old from Brazil, Colombia, Honduras, Mexico and Puerto Rico.
Dengue is caused by four distinct virus serotypes transmitted by mosquitoes. It is a threat to nearly half of the world's population. Currently, there is no specific treatment available for dengue. It is a health priority in many countries of Latin America and Asia where epidemics occur regularly. The WHO estimates up to 100 million infections per year; however, the overall number of people infected with dengue globally is not fully known. The WHO has set the goal of estimating the true public health burden of dengue by 2015. Dengue is underreported because the disease is often misdiagnosed due to a large spectrum of clinical symptoms from mild non-specific illness to life threatening complications and because of the limitations of the surveillance systems.
Each year, an estimated 500,000 people, including children, with severe dengue require hospitalisation. About 2.5 per cent affected would die.3 Severe dengue (also known as dengue haemorrhagic fever) is a potentially deadly complication due to plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment.2 Dengue places tremendous pressure on health systems and straining medical resources resulting in significant economic and social impact. Timely access to appropriate health care is critical to reduce the risk of mortality in case of severe dengue. The WHO has set the target to reduce dengue mortality by 50% and reduce morbidity by 25% by 2020.
(World Health Organization (WHO). Global strategy for dengue prevention control: 2012-2020. Available at: http://reliefweb.int/sites/reliefweb.int/files/resources/9789241504034_eng.pdf. Published 2012. Accessed April 3, 2014)
About the Phase III clinical study conducted in Asia
The Phase III clinical study conducted in Asia is a randomised, observer-blind, placebo-controlled multicentre trial. A total of 10,275 children aged 2 to 14 years from dengue endemic areas of Indonesia, Malaysia, the Philippines, Thailand and Vietnam participated in the study from 2011-2013 and were randomised to either receive three injections of the dengue vaccine or a placebo (2 to 1 ratio) at 6-month intervals. The primary endpoint was measured by the number of symptomatic virologically-confirmed dengue cases caused by any serotype. The study will continue with a long term follow up of the study population until 2017.
Sanofi Pasteur has been working on a dengue vaccine for more than 20 years. The company's goal is to make dengue the next vaccine-preventable disease with a safe and effective dengue vaccine accessible in all regions of the world where dengue is a public health issue.
Over 40,000 volunteers are participating in the Sanofi Pasteur dengue vaccine clinical study program (Phase I, II and III).
Two pivotal Phase III efficacy studies involve more than 31,000 volunteers from Asia (Indonesia, Malaysia, the Philippines, Thailand and Vietnam) and Latin America (Brazil, Colombia, Honduras, Mexico and Puerto Rico). The Phase III evaluations provide pivotal data on efficacy, safety, and immunogenicity of the vaccine candidate in a broad population and different epidemiological environments and assess the potential public health impact of the vaccine on the disease burden.
- World Health Organization (WHO). Global strategy for dengue prevention control: 2012-2020. Available at: http://reliefweb.int/sites/reliefweb.int/files/resources/9789241504034_eng.pdf. Published 2012. Accessed April 3, 2014