Dengue Vaccine in Thailand and South Africa

Dengue Vaccine in Thailand and South Africa

Overview of the Disease

Dengue fever or dengue disease is a viral infection transmitted by the Aedes aegypti or Aedes albopictus mosquito, the same mosquito species which transmits the Zika, yellow fever and chikungunya viruses. The Aedes species of mosquito lives in warmer areas of the world, including the Americas, the Caribbean, Western Pacific Islands, Australia, Asia, Oceania, Africa and the Middle East making countries in these areas highly susceptible to mosquito-borne infections such as dengue^[i]. Each year approximately 400 million people globally are affected by dengue and 100 million people (or 25%) present symptoms (i.e., get sick), resulting in 22,000 deaths. The level of risk for prevalence of dengue fever for Thailand remains frequent and continuous while in South Africa there is no evidence of a level of risk^[ii].

Dengue fever is caused by four different subspecies, or serotypes, of the virus family Flaviviridae, including DEN-1, DEN-2, DEN-3 and DEN-4. Classified as an acute febrile disease, dengue presents with flu-like symptoms. These symptoms can be mild or severe and include nausea, vomiting, rash and joint pain. In the most severe cases dengue fever can lead to death.

There is currently no specific medicine available to treat dengue infection once contracted, so symptoms must be managed^[iii]. Symptom management is available in a variety of ways, including over-the-counter medicines such as pain relievers with acetaminophen, rest, and hydration. Once recovered, the previously infected individual gains indefinite immunity against the particular serotype that caused the infection and temporary immunity against the other serotypes[iv].

In 2016 the first dengue vaccine became commercially available in 11 countries, including Thailand. This vaccine, Dengvaxia, is produced by French pharmaceutical company Sanofi Pasteur and is currently the only licensed vaccine available to prevent Dengue fever^[v]. However, in 2017 Sanofi revised its vaccine recommendations to include only those who have had a previous dengue infection as the vaccine can worsen future outcomes for those not yet infected^[vi].

Market Size/Disease Burden

Thailand

Dengue fever is currently endemic in Thailand.  The Thailand Ministry of Public Health indicated that there were over 44,000 dengue fever patients and 62 associated deaths[vii] in the first six months of 2019^[viii]. In Thailand, the direct costs of hospitalizations related to dengue fever is approximately USD $573[ix]. The average morbidity costs associated with dengue in Thailand is approximately $599. Patients lost approximately 4.1 days of school or 8.8 working days in order to be treated.

South Africa

Dengue fever is currently not endemic in South Africa, but there have been increases in the introduction of dengue cases from endemic countries into South Africa[x]. Between 2000 and 2016, 119 confirmed dengue cases in South Africa occurred in travelers with known travel history. Their sources of infection were Southeast Asia (38%), parts of Africa (29%), India and South-central Asia (20%), Latin America, Central America and the Caribbean (10%) and Oceania (3%). Countries from which the largest numbers of cases originated were Thailand (31), Angola (18), India (18) and Brazil (7).

Company Overview: Sanofi Pasteur

Sanofi Pasteur currently produces the only licensed vaccine available to prevent dengue fever infection called Dengvaxia^[xi]. Dengvaxia is the first FDA approved vaccine for “the prevention of Dengue disease caused by all Dengue virus serotypes (1, 2, 3 and 4) in people ages 9 through 16 who have laboratory-confirmed previous dengue infection and who live in endemic areas”^[xii].

While Dengvaxia is the only vaccine currently available, it has some serious limitations. The Dengvaxia vaccine must be administered over three separate injections: the initial dose is followed by a second dose at 6 months and a third dose at 12 months. Dengvaxia must also be given only to patients who have been previously infected with at least one dengue virus serotype. If a patient who had not been previously infected received the Dengvaxia vaccine it could result in a potentially more severe infection in the future^[xiii].

Company Competitors

The global dengue vaccine market is consolidated in nature, with Sanofi Pasteur currently holding the monopoly with its product, Dengvaxia, which has been approved in 15 countries. However, research and development efforts are underway by competing international pharmaceutical companies such as Takeda Pharmaceuticals, Merck Sharp & Dohme and GlaxoSmithKline, to develop new dengue vaccines and challenge Sanofi Pasteur’s monopoly in the market^[xiv].

As of mid-2019, there are approximately five dengue vaccines  in development. The most promising vaccine, which is in phase 3 trials, is the DENVax/TAK-003 vaccine developed jointly by Inviragen and Takeda. The DENVax/TAK-003 vaccine shows promising results as potential patients would not have to have had a previous dengue infection to be eligible to receive the DENVax/TAK-003 vaccine. Additionally, new technological approaches, such as virus-vectored and virus-like-particle (VLP) based vaccines are under evaluation in preclinical studies^[xv].

Market Size of Solution

Thailand

After Sanofi Pasteur updated its recommendations in 2017 to limit the vaccine to only those who had already had a dengue infection (a positive serostatus), its target market population dropped dramatically. The available target market no longer includes the majority of the population but instead is focused on only those who can be confirmed as having a positive serostatus. This is complicated because confirming serostatus involved blood testing, which can be expensive and time-consuming and provides additional barriers to access for potential vaccine recipients, especially those in rural areas.

South Africa

In South Africa the market size is incredibly small, as dengue fever is not endemic to South Africa, and current cases are mainly due to travel to endemic neighboring regions. As this vaccine can only be given to those who have already been exposed to the dengue virus, only a limited number of regular travelers to endemic regions would have a need for testing and subsequent vaccination.

Barriers to Access and Other Concerns

For the Dengvaxia vaccine to be effective the individual receiving the vaccine must have already had the dengue virus in the past. Also, the United States FDA recommends the vaccine be administered to individuals between 9 and 16 years of age. This will exclude a significant population of patients that would benefit from a vaccine against dengue. For example, newborn and young children (below 9 years) never having dengue would not be likely candidates to receive the Dengvaxia vaccine. Also, the vaccine must be administered over three separate doses which may reduce the likelihood of completing the full treatment.

Thailand

Thailand’s publicly funded healthcare system poses several concerns for the Dengvaxia vaccine. First, Thailand has weaker intellectual property rights compared to other nations. The government’s previous decisions to override international drug patents in favor of compulsory licenses is a risk to Sanofi, as it could detract from the firm’s market share and the Dengvaxia’s intellectual property could leak.[xvi] In addition, there is a growing financial burden on Thailand’s public healthcare system. To alleviate stress on the system, authorities disclosed plans in 2015 to shift towards a co-payment system. This could price-out a segment of the population in need of the Dengvaxia vaccine. Finally, distributing through the public sector ties Sanofi to risks of political instability in Thailand.

South Africa

Both Thailand and South Africa will struggle with distributing the Dengvaxia vaccine outside of major metropolitan areas and to poorer segments of their populations.

Appendix

References

^[i] Dengue Around the World | Dengue | CDC. (n.d.). Retrieved from https://www.cdc.gov/dengue/areaswithrisk/around-the-world.html

^[ii] Dengue Around the World | Dengue | CDC. (n.d.). Retrieved from https://www.cdc.gov/dengue/areaswithrisk/around-the-world.html

^[iii] Dengue Around the World | Dengue | CDC. (n.d.). Retrieved from https://www.cdc.gov/dengue/areaswithrisk/around-the-world.html

[iv] Global Strategy for Dengue Prevention and Control, 2012-2020. R. Velayudhan, World Health Organization, 2012, https://www.who.int/denguecontrol/resources/9789241504034/en/

^[v] Questions and Answers on Dengue Vaccines. (2018, April 24). Retrieved from https://www.who.int/immunization/research/development/dengue_q_and_a/en/

^[vi] http://www.cidrap.umn.edu/news-perspective/2017/12/sanofi-restricts-dengue-vaccine-downplays-antibody-enhancement

[vii] https://reliefweb.int/report/thailand/moph-tackles-dengue-fever-after-62-deaths-reported

^[viii] https://reliefweb.int/report/thailand/moph-tackles-dengue-fever-after-62-deaths-reported

[ix] Cost of Dengue Cases in Eight Countries in the Americas and Asia: A Prospective Study (Am I Trop Med Hygiene)

[x] http://www.nicd.ac.za/wp-content/uploads/2017/03/Increased-importation-of-dengue-cases.pdf

^[xi] Questions and Answers on Dengue Vaccines. (2018, April 24). Retrieved from https://www.who.int/immunization/research/development/dengue_q_and_a/en/

^[xii] Commissioner, O. of the. (n.d.). First FDA-approved vaccine for the prevention of dengue disease in endemic regions. Retrieved from https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-dengue-disease-endemic-regions

^[xiii] Commissioner, O. of the. (n.d.). First FDA-approved vaccine for the prevention of dengue disease in endemic regions. Retrieved from https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-dengue-disease-endemic-regions

^[xiv] “Top 4 Vendors in the Global Dengue Vaccine Market ….” Accessed September 21, 2019. https://www.businesswire.com/news/home/20171216005023/en/Top-4-Vendors-Global-Dengue-Vaccine-Market.

^[xv] “Dengue Vaccines Market History and Forecast 2018-2027, By ….” Accessed September 21, 2019. https://www.marketwatch.com/press-release/dengue-vaccines-market-history-and-forecast-2018-2027-by-companies-key-regions-2019-01-23.

[xvi] Thailand Pharmaceuticals & Healthcare Report – Q1 2017. Fitch Solutions Group Limited, London, 2017. ProQuest, http://proxy.lib.umich.edu/login?url=https://search-proquest-com.proxy.lib.umich.edu/docview/1846515591?accountid=14667