World’s First Dengue Vaccine Dengvaxia into Market Plight

By Mr. Nanguo

Awkward situation of sales of Dengvaxia

Performance of the dengue vaccine—Dengvaxia that is placed high hopes on by Sanofi is not optimistic, although the dengue is still running riot. Marketed at the end of 2015, Dengvaxia only had EUR 55 million sales in 2016, far lower than the anticipated EUR 200 million; and its situation is even worse this year: its sales only reached EUR 22 million in the past three quarters, wherein, the sales were only EUR 4 million in Q3, down by nearly 90% compared to the same period of last year.

Dengvaxia took Sanofi 20 years and nearly USD 1.5 billion to develop. Regarding the current awkward situation of bleak sales, the company’s spokesperson blamed it on the economic woes and political instability of high incidence regions of dengue. Indeed, such regions are tropical countries and regions, such as Brazil, Philippines, and some Caribbean countries, which are mostly developing country, with weak economy and political instability, resulting in not much support in vaccination offered from the country level. In addition, WHO’s warning on Dengvaxia is also nonnegligible: WHO vaccine experts have warned repeatedly that people in regions with low incidence of dengue should be cautious about receiving vaccination of dengue vaccine, especially those not having had dengue, because the side effects after the vaccination might outweigh the expected benefits.

Threat from the competitor TAK-003

Sanofi is endeavoring to promote Dengvaxia, however, for now, it has not achieved the expected results. More importantly, its competitor has not slowed down. The dengue vaccine TAK-003 of Takeda has posed a strong challenge for Sanofi. There were 1,794 adolescents and children aged 2-17 from countries with high incidence of dengue—Dominica, Panama and Philippines who participated in the Phase 2 clinical trial in the past 18 months. According to the data published on Lancet, there would be the antibody for four subtypes of dengue virus after vaccination; and populations never having dengue would have high antibody after vaccination of two doses of TAK-003. Researchers will continue to track the changes of the positive antibody inside subjects in the next 2 years. Takeda has determined the vaccination schedule of TAK-003 to be two doses at interval of 3 months through the Phase 2 trial. The Phase 2 results are encouraging, however, there shall still be a large Phase III clinical trial that includes 20,100 subjects, to validate the vaccine effectiveness. The excellent Phase 2 results have raised pressure on Sanofi.

Prevention and control of dengue from the source

Besides the direct competitor, the U.S. Environmental Protection Agency (EPA) has recently approved the biotechnology company MosquitoMate to control wild populations, and reduce infection of dengue and Zika, etc. by using the Aedes albopictus infected by the harmless bacterium Wolbachia pipientis.

Wolbachia-infected male Aedes albopictus that are released to the environment will mate with wild females that do not carry Wolbachia, resulting the fertilized eggs inside the females to not hatch; and the objective of reducing population number will be finally reached as the infected males continue to be released. The company tested the action of Wolbachia on Aedes albopictus in three states in the paste three years, and such method reduced more than 70% mosquito populations in those areas.

The dengue transmission in the abovementioned high incidence countries will be reduced from the source once the modified mosquitoes of MosquitoMate Company are promoted there; and as the dengue infection scale decreases, it will affect people’s enthusiasm for vaccination, to further compress the space of Dengvaxia.

In my opinion: It seems that whether the chasing threat or the prevention and control of dengue from the source with the modified mosquitoes could not affect the sales of Dengvaxia in the short term, for which the real reason lies in the poverty of countries in main regions of dengue outbreak that leads to insufficient purchasing power. In addition, the own ADE (antibody-dependent enhancement) after dengue virus infection may worsen the condition after repeated dengue virus infection if after a healthy person receives vaccination, the neutralizing antibody titer against certain serotype of dengue virus is not ideal, which is the reason why WHO officials have been warning healthy people in regions not with high incidence to be cautious about vaccination. And even those healthy people in high incidence regions are also cautious about vaccination, which makes the relevant sales increasingly difficult on the mainstream European and American pharmaceutical markets. From this, the possible safety issue of the vaccine itself is the key factor.

About the author: Mr. Nanguo, doctoral candidate, based on the immunology area, has been engaged in research of vaccines and antibody drugs for years; participated in research of microneedle vaccine transdermal drug delivery system, and fundamental research of therapeutic hepatitis B vaccines, etc.; now insists on the research in the biomedical field, focuses on antibody drugs, and has in-depth research of immunotherapy and bispecific antibody fields.