WHO Prequalifies Takeda’s Qdenga Dengue Vaccine

• by Marco Cáceres and Barbara Loe Fisher

• Published May 28, 2024
• Vaccines

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On May 10, 2024, the World Health Organization (WHO) granted prequalification status to the Qdenga (TAK-003) dengue vaccine, developed by Takeda Pharmaceutical Company Ltd. of  Tokyo, Japan. The live attenuated virus vaccine is recommended to be given in two doses three months apart to children six to 16 years old living in areas where dengue fever disease is endemic. It is designed to protect against four types of dengue: dengue 1, 2, 3, and 4.^{1 2 3 4 5 6 7}

According to the U.S. Centers for Disease Control and Prevention (CDC), the disease affects people living in tropical and subtropical areas of the world and “up to 400 million people are infected by a dengue virus” after being bitten by infected Aedes mosquitoes. Symptoms of the disease include a fever and aches and pains in muscles, joints, bones and eye pain typically behind the eyes; nausea and vomiting; and rash. There is no specific medicine to treat dengue and most people will recover within a week.⁸

Prequalification signifies that the WHO has assessed the quality, safety and efficacy of the vaccine. It opens the way for governments and organizations around the world to purchase supplies of Qdenga for distribution.^{6 7}

According to Rogerio Gaspar, PhD, director for regulation and prequalification for the WHO:

The prequalification of Aedes is an important step in the expansion of global access to dengue vaccines, as it is now eligible for procurement by UN agencies including UNICEF and PAHO. With only two dengue vaccines to date prequalified, we look forward to more vaccine developers coming forward for assessment, so that we can ensure vaccines reach all communities who need it.^{2 3 4 5 7}

Qdenga is the second dengue vaccine authorized by the WHO. The first was Dengvaxia (CYD-TDV), developed by Sanofi Pasteur SA of Paris, France. Dengvaxia, also a live attenuated virus vaccine, was approved by the U.S. Food and Drug Administration (FDA) on May 1, 2019. But Dengvaxia has experienced some problems. In 2017, Sanofi Pasteur announced that the vaccine could lead to more severe cases of dengue fever in some individuals. An 2018 article in The Vaccine Reaction noted that studies on Dengvaxia revealed that giving the vaccine to people who had never contracted dengue “leaves them vulnerable to a severe reaction if they subsequently contract the disease.”^{9 10}

A study on Dengvaxia published in the journal Nature on Apr. 15, 2023 confirmed:

[T]he optimism that a dengue vaccine was finally available quickly became disappointment when a safety signal was observed in vaccine recipients who were dengue non-immune at the time of vaccine administration. In the third year of the phase III clinical trial, the youngest, non-immune vaccine recipients experienced increased rates of hospitalized and severe dengue compared to their unvaccinated peers.¹¹

On the CDC’s website, which was updated in January 2022, at the top of the page on dengue vaccination, there is a boxed warnng on use of Dengvaxia stating:

Sanofi Pasteur will stop manufacturing its dengue vaccine for children. The manufacturer is discontinyuing the vaccine citing lack of demand in the global market to continue production of this vaccine. CDC, in collaboration with the Puerto Rico Department of Health, will continue alerting health professionals about the discontinuation of Dengvaxia and the use of this vaccine as recommended by the Advisory Committee on Immunization Pratices (ACIP). Denvaxia is safe and effective when administered as recommended. There are two other dengue vaccines either approved or in late stages of development. However, they are not currently available in the United States. People can continue to protect themselves and their families from dengue by preventing mosquito bites and controlling mosquitoes in and around their homes.¹²

Qdenga is intended to be an improvement over Dengvaxia. Reportedly, so far it has not been found to have similar problems as the Sanofi vaccine. Research suggests Takeda’s dengue vaccine, which was approved by the European Medicines Agency (EMA) in 2022, is 84 percent effective in preventing hospitalizations due to dengue and 61 percent effective in reducing symptoms of the disease.^{1 2}

FDA Granted Takeda a Priority Review of Qudenga Dengue Vaccine

The FDA accepted and granted priority review of Takeda’s Biologics License Application (BLA) for Qdenga on Nov. 22, 2022.¹³

However, following discussions with the FDA, Takeda voluntarily withdrew its BLA for Qdenga on July 11, 2023 citing “data collection issues” that could not be addressed within the review cycle period. The FDA had reportedly requested additional data that was not included in the double-blind, randomized, placebo-controlled Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial.^{14 15 16} The company stated:

The future plan for TAK-003 in the US will be further evaluated given the need for travelers and those living in dengue-endemic areas of the U.S., such as Puerto Rico.^{14 16}

Takeda is evaluating the requirements for resubmitting a BLA for Qdenga with the FDA. The company is initially looking to distribute Qdenga in some 25 countries.

Dengue Infection Rates Much Higher Than Two Decades Ago

Dengue is endemic in more than 125 countries and infection rates are eight times higher now than they were two decades ago. Takeda anticipates strong market demand for the vaccine around the world and estimates its product could generate $1.6 billion to $2 billion in sales revenue.^{14 17}

On May 10, 2024, the Pan American Health Organization (PAHO) published a Situation Report confirming 6,769,140 suspected cases of dengue in 2024. The report attributed 1,733 deaths to the disease worldwide last year.¹⁸

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