Dengvaxia: The world's first anti-dengue vaccine

In April, the Department of Health (DOH) launched the first school-based dengue immunization program on Monday with around 250 Grade 4 students of Parang Elementary School in Marikina City.

The DOH chose Grade 4 students from the National Capital Region, Calabarzon, and Central Luzon four regions with the highest number of dengue cases.

The vaccine called Dengvaxia, took scientists 20 years to develop and is considered the world’s first anti-dengue vaccine, and the Philippines is the first country where it is commercially available.

Dengue is a high-motile and ongoing public health concern in the Philippines. The first known epidemic of severe dengue or dengue hemorrhagic fever anywhere in the world was recorded in Manila in 1953.1 By the mid 19705 severe dengue had become a leading cause of hospitalization and death among children in the region 2 Between 2004 and 2010, the Philippines experienced the seventh highest number of dengue cases in the world according to the World Health Organization (WHO).

In 2013, DOH reported 204,906 cases of dengue, the highest number recorded since the establishment of the National Dengue Prevention and Control Program in 1993. More than 200,000 dengue cases were reported in the Philippines in 2015, 80,000 more than were reported in 2014. In both September and October 2015, the number of reported cases rose above the epidemic threshold. d

Although the number of reported dengue cases slightly decreased in 2014, the 2015 data suggest an increasing trend in cases in the coming years. Recent data gathered by the Department of Health from January to 24 September this year shows an increase of 11.5 percent year on year across the country, with t otal dengue Infections at 142,247 compared to 127,525 last year and 604 recorded fatalities.

Based on Philippine surveillance data collected between 2011 and 2015, an average of 220 dengue cases were reported in the country every day.8 In 2015, almost 50% of reported cases came from three most urbanized regions Region 3 (17.6%), Region 4 (17.3%), and the National Capital Region (12.6%).9 Cases stemming from all four serotypes of dengue were reported in 2015.

Disease burden: US$345 million per year

The economic burden of dengue in the Philippines is substantial. A study published in 2015 estimated that between 2008 and 2012. clinically diagnosed dengue cases in the Philippines were associated with a direct medical cost (in 2012 US dollars) of $345 million annually. The study calculated the average cost of treatment per case to be $409, representing 16% of the Philippines’ 2012 per capita GDP. Sixty-live percent of cases were treated in inpatient hospitals, representing 90% of direct costs.

In addition to dengue‘s burden on a household, the illness can adversely impact a country’s economy through a loss of productivity caused by the illness and pre-mature death, increased healthcare costs and a possible reduction in tourism.

DENGVAXIA THE FIRST DENGUE VACCINE (Source)

Sanofi Pasteur’s vaccine is the culmination of over two decades of scientific innovation and collaboration, as well as 25 clinical studies in 15 countries around the world. Over 40,000 volunteers participated in the Sanofi Pasteur dengue vaccine clinical study program (phase I, II and III), of whom, 29,000 volunteers received the vaccine. Dengvaxia successfully completed phase III clinical studies in 2014 to evaluate the primary objective of vaccine efficacy.

Long-term follow-up studies of the vaccine, recommended by WHO for all dengue vaccines in development, are currently ongoing. Additional pooled efficacy and integrated safety analyses from the 25-month Phase III efficacy studies and the ongoing long-term studies, respectively, were recently published in The New England Journal of Medicine reconfirming the vaccine’s consistent efficacy and longer-term safety profile in populations 9 years of age and older. In a pooled efficacy analysis in volunteers aged 9-16 who participated in the two Phase III 25-month efficacy studies, Dengvaxia was shown to reduce dengue due to all four serotypes in two-thirds of the participants. Furthermore, this pooled efficacy analysis showed that Dengvaxia prevented 9 out of 10 cases of severe dengue and 8 out 10 hospitalizations due to dengue in this age group.

Dengvaxia is the first vaccine licensed for the prevention of dengue in the world. First doses of the vaccine have been produced and full scale production capacity will be reaching 100 million vaccine doses annually.

Seasonality and global climate change

Dengue has become a year-round threat in the Philippines. However, data suggests that the number of dengue cases increases one to two months after the onset ofthe rainy season, resulting in a peak of dengue cases between July and November each year.13

The Philippines is severely affected by extreme weather events and is vulnerable to the effects of climate change Vector-borne diseases like dengue may be particularly sensitive to both periodic tiuctuations and sustained changes in global and local climates.“ Additionally, a study examining data from eight Asian countries including the Philippines over 18 years revealed a strong correlation between regional dengue epidemics and elevated temperatures associated with El Nino.

In a recent vaccine cost-effectiveness study performed by Professor Hilton Lam of the UP-National Institute of Health, a nationwide annual routine vaccination of nine year olds starting in 2016 would lead to an estimated 24.2 reduction in dengue cases in the country over a five year period. This would translate to 775,053 avoided cases of dengue, 502,000 avoided hospitalizations, 22,010 avoid deaths and almost P21 billion in avoided cost to society.

Beyond the Vial: A Social Value Business Model For Sanofi Pasteur’s Dengue Vaccine

Dr. Su - Peing Ng, Global Medical Director of Sanofi Pasteur is joined by Lee Kuan Yew School of Public Policy Professor Tikki Pang at a recent launch of Sanofi’s dengue vaccine, Dengvaxia last Sept 20 at New World Hotel Makati with Sanofi officials and media.

Dr Su-Peing Ng and Professor Tikki Pang discussed with members of the press the latest scientific evidence or data on the dengue vaccine and how it prevented the rise of dengue fever in the country.

Dengue is a serious and complex disease. The mosquitos that transmit dengue indiscriminately pass the disease amongst people of all ages and socio-economic levels.  About half of the world’s population lives in areas where dengue is endemic, and millions suffer its seemingly bone-breaking pain and severe fevers, each year. Its reach has grown 30-fold in the last 50 years, swelling with globalization, urbanization, and climate change. Global costs of dengue are around $9 billion, annually . But in the years ahead, the tide of dengue could be better controlled through enhanced international collaborations in public health, and an innovative social business model with a vaccine at its core.

         
Twenty years ago, Sanofi Pasteur identified the potential scale of the dengue problem at its early stages, and began to put in place a set of innovative scientific and industrial solutions. In 2015, the dengue vaccine received its first market approvals.  In July 2016, after more than two years of review processes and inputs from clinical trial data and from top global dengue and infectious diseases experts, the World Health Organization issued its recommendation that countries where the dengue burden is high should consider vaccine introduction as part of integrated dengue prevention and control measures. As of September 14th 2016, the vaccine waslicensed in 9 endemic countries in Asia and Latin America  and public immunization programs are underway in Brazil and the Philippines, while the vaccine is also available on the private markets in those countries as well as in Mexico and El Salvador.

The story behind the vaccine is one of hard-earned research and development – but you’ve heard that story before. This story goes beyond the vial, as well: It’s about a new, social value business model that Sanofi Pasteur has built in collaboration with dengue-endemic countries and global health institutions. In time, it can help control dengue. But as importantly, it can help to support better healthcare outcomes in emerging markets by accelerating access to needed innovations.

When Sanofi Pasteur first identified a viable dengue vaccine candidate, we saw the opportunity to develop a health solution specifically for the countries where the dengue burden is highest.  We wanted to make sure that people who lived in grip of dengue’s threat were the people for whom the vaccine is designed and delivered primarily.  It sounds simple enough but in traditional pharmaceutical business models, this is often not the case.  More often than not, travelers and other select groups of individuals from high-income countries have access to new preventive tools against tropical diseases first, at a premium, before these solutions are made available, often as many as 10 years later, in less rich economies, even if this is where the disease burden is heaviest.

Our faith in this“flipping the model” approach was inspired by the scale of the dengue problem. Vaccines are widely considered among the most effective healthcare interventions against infectious diseases. They often confer protection against a disease that extends beyond the vaccinated to also the unvaccinated population. Given dengue’s massive spread, a vaccine could help national authorities in dengue-endemic countries achieve WHO 2020 objectives for dengue reductions in mortality (50%) and morbidity (25%) if it is implemented in large-scale public health programs1.

We anticipated this, and began building robust public health collaborations and industrial resources essential to success. The global clinical development program of the vaccine included 40,000 participants in 15 countries across Asia and Latin America ,  ,  . We invested in extensive skills training for healthcare personnel, upgraded healthcare facilities and increased prevention and education efforts. We captured new scientific insights into dengue epidemiology and transmission which is shared with host governments.  In parallel, Sanofi Pasteur built a dedicated dengue-vaccine production facility that will allow large and cost-effective supply to support optimal uptake of the vaccine as needed around the world.

Successful implementation of dengue vaccination programs can help governments in dengue-endemic countries to take control over the disease. Mathematical modeling of the vaccine’s impact indicate  that if countries take up broad public vaccination programs in highly dengue-endemic countries like those that participated in the Phase III development of the vaccine, vaccination can help cut the burden of disease in half over five years . Healthcare systems’ loads can be lightened and they can attract further outside public health investment with demonstrated program results. Successful vaccination programs therefore have the potential to be catalysts for social and economic progress.  Today, states like Paraná in Brazil are taking up the lead in this effort.  Public program introduction of the dengue vaccine in Mexico has been recommended by CONAVA, that country’s National Vaccination Council. Countries like these that have participated in the clinical development of the vaccine can see the value in the entire process as well as in the potential future results.

At Sanofi Pasteur, we welcome enhanced support and investment in the robust public-private collaborations that ensure broad reach for innovative health solutions like the dengue vaccine. Working together to establish balanced trust and long-term commitment to new ways of bringing innovation to people is critical to unlocking innovative business models’ fullest potential for improving public health worldwide.