Where is the dengue vaccine?

Per Susana van der Ploeg It is Caroline Scopelfor the column Health is not a commodity

In this article, the Working Group on Intellectual Property (GTPI) sets out to answer a recurring question: where is the dengue vaccine? We also want to present what we can call commercial determinants in controlling the disease: monopoly, limited production and high prices. Over the years, there have been several initiatives to develop vaccines against dengue, which for various reasons did not result in commercially viable products.

In 2015, the first health registration of a vaccine against dengue in Brazil was granted, Dengvaxia, from the company Sanofi. However, this vaccine is only recommended for people who have already had the disease, as in others, vaccination increases the risk of worsening the disease. For these reasons, it is not a viable vaccine for the public health system, as it does not fulfill the essential function of reducing the costs associated with treatment and complications of the disease.

In 2023, a dengue vaccine called Qdenga was registered by the Japanese company Takeda and incorporated into the SUS National Immunization Plan. However, the company’s limited capacity to supply the vaccine, which will only provide 5 million doses throughout 2024, limited the vaccination campaign to just 521 municipalities, around 10% of the total, and reduced population groups , for children between 10 and 14 years old, even though it was approved for a wider audience from 4 to 60 years old.

There are alternatives that would allow vaccination coverage to be increased. Why is there only one company, with limited production capacity, making the dengue vaccine available in the SUS, while we are witnessing an uncontrolled epidemic throughout the country? We have been living with the dengue epidemic in Brazil for 40 years. Why do we depend on a Japanese company? Dependence on a single manufacturer, due to the patent monopoly granted by the State, is a risk to public health and undermines control of the epidemic.

What is dengue and how does it affect the country

Dengue is a viral disease transmitted by an arthropod vector, the mosquito Aedes aegypti. The dengue virus belongs to the arbovirus family and four serotypes are known, called DENV-1, DENV-2, DENV-3 and DENV-4. Like other mosquito-borne diseases, the transmission of dengue fever and its epidemics is directly associated with climatic factors, especially the rainy season, which occurs in Brazil between October and May. However, climate change and urbanization conditions in large centers worsen the spread of the disease, which affects social classes unequally. Marginalized populations have a higher incidence of the disease, especially in large cities.

The way of organizing life in cities, the occupation of urban space, the great Brazilian social inequality, sanitation and inadequate treatment of urban waste, drainage and water flow, population growth, increased density and distribution of vectors and barriers to accessing public health care are factors that facilitate the transmission and endemic maintenance of dengue in Brazil.

In the first week of April, Brazil recorded the highest number of confirmed dengue deaths in a single year, since the beginning of the historical series in 2000. In relation to the number of cases, 2024 has already surpassed previous years. Until the 11th week of the year, the Ministry of Health registered more than 2.9 million probable cases of the disease.

Dengue symptoms, such as fever, headache, prostration, muscle and/or joint pain and pain behind the eyes, are common and suddenly debilitating manifestations, impacting the disease burden. While many people recover well, certain populations face a higher risk of complications and even death, including pregnant or breastfeeding women, children under age 2, and seniors over age 65.

However, the majority of these fatalities could be avoided, with prevention and treatment actions, highlighting the crucial importance of the quality and organization of health services. This raises serious concerns, especially for the most vulnerable communities, who often face significant difficulties in accessing these essential services. This disparity in healthcare responses highlights the deep social inequalities that persist and require urgent political action to ensure protection and equitable access to healthcare for all citizens.

There is no specific drug treatment for dengue fever. The main recommendation for the classic form of dengue is hydration, rest, control of symptoms, especially pain and fever, and monitoring of signs; in case of severe dengue, hospitalization, parenteral fluid replacement and monitoring of venous pressure may be necessary. The lack of specific treatment and the difficulties in controlling the spread of the vector make vaccinating the population an important tool for controlling dengue epidemics.

Vaccination – and how it could have happened before

It is important to highlight that vaccination is a public health measure. Mass vaccination is an effective way to prevent epidemic and pandemic outbreaks. By maintaining high immunization rates in the population, it is possible to stop the spread of pathogens and prevent the uncontrolled spread of diseases.

Vaccination in the private sector, which aims at individual protection, is not capable of producing the same impact on public health as campaigns coordinated by the public health system, due to unequal access, lack of coordination, and lack of a systemic approach and focus on profit. In contrast, vaccination campaigns coordinated by the national immunization system (SNI) tend to be more comprehensive, equitable and effective in promoting public health.

The Qdenga vaccine, produced from the attenuated virus, is not in itself a new technology. The first vaccine in history, the smallpox vaccine, developed more than 230 years ago, already presented the concept of an attenuated virus. The polio vaccine, developed by Jonas Edward Salk, was developed with the “dead” virus in 1955. Salk, when asked who the patent belonged to, replied: “Who owns my vaccine? To the people! Can you patent the sun?” Vaccination is an essential public health measure to save lives. As long as profit is put first, the epidemic will remain uncontrolled.

As we learned in the Covid-19 pandemic, increasing production capacity, lowering prices and expanding vaccine supply are fundamental steps to guaranteeing access to technology for those who need it. Technology transfer can be an alternative to address the issue of access to the dengue vaccine in the SUS. In addition, there is also the possibility of supplying the vaccine from the Butantan Institute, which still depends on approval from the National Health Surveillance Agency (Anvisa).

The dependence on a single manufacturer or technology transfer processes occurs because the products are protected by several patents – some even owned by the United States government – ​​arising from research carried out with public investment. In Brazil, there are at least 50 patent applications related to dengue vaccines, filed with the National Institute of Industrial Property (INPI), which restrict research, production and access, as shown in Figure 1 at the end of the text.

Overlapping patent applications is a strategy commonly used by pharmaceutical companies to extend their monopoly and maximize their profits; If all these patent applications for the dengue vaccine were granted in Brazil, this would result in a market monopoly until 2041, lasting 45 years. Mapping and monitoring the patent status are important tools for understanding the patent status of products, helping to formulate strategies to overcome this barrier and provide access to the population.

Furthermore, even after the validity period of these patents, the mass commercialization of these vaccines would be difficult, as in Brazilian legislation there is no possibility of registering vaccines as generic or biosimilar products, which means that for the registration of a new vaccine a long and expensive process of clinical and industrial development of the product is required.

The fight against dengue in Brazil is a complex battle that goes beyond public health issues. The uncontrolled epidemic and limited access to vaccination raise serious concerns about gaps in the healthcare system. The dependence on a single manufacturer, the barriers imposed by patents and the lack of policies that facilitate the large-scale production and distribution of vaccines are challenges that need to be faced.

Transferring technology to public laboratories or approving vaccines from other sources are potential solutions to expand access to vaccination and effectively control the spread of the disease. Ultimately, public health must not be held hostage by commercial interests, urgent measures are needed to ensure that protection and equitable access to healthcare are a reality for all citizens.

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Figure 1: Life cycle of the patent monopoly on the dengue vaccine in Brazil, based on patent applications filed with the INPI and an estimated 20 years of monopoly. Patent applications in gray are extinct or archived, in green they are rejected, in yellow they are pending and in red they are granted. This patent mapping, which was constructed from the cross-referencing of publicly available information, is not intended to be exhaustive, but is intended to exemplify the overlapping of patent applications in Brazil.