Taking the next step toward challenging Sanofi’s first-to-market Dengvaxia, on Wednesday, Takeda kicked off a global Phase III trial of its dengue vaccine, TAK-003. The announcement comes just days after the company pushed into another mosquito-borne disease, Zika, through a $312 million R&D deal with the U.S. government.

Takeda vaccinated the first subject in a dengue study that’ll include more than 20,000 participants aged 4 to 16 in endemic nations in Latin America and Asia. It’s a “critical milestone” in efforts to bring the candidate--a live-attenuated tetravalent dengue vaccine--to market, Takeda vaccines head Rajeev Venkayya said in a statement.

With the study, Takeda is embarking on a new effort to take its vaccines business global, the Financial Times reported. Analysts have estimated dengue vaccines could be a $1 billion market or more per year, but Sanofi's Dengvaxia launch has faltered and another potential rival is already in Phase III testing in Brazil. It's unclear whether the market would be big enough for all three vaccines.

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TAK-003 will be administered in two doses 90 days apart as part of the double-blind, placebo-controlled trial. Investigators will look at vaccine efficacy in all four dengue serotypes “regardless of age and whether the individual has previously been exposed to the virus,” Takeda said in a statement.

That last point could prove to be important, as a new study this week demonstrated that Dengvaxia can lead to more serious dengue infections if it’s used in areas where the disease isn't common. Dengue infections tend to be more serious the second time around, researchers said this week.

If Dengvaxia is administered to a person who hasn’t previously been infected, the vaccine “acts very much like a natural infection but without making recipients sick,” the scientists said in a release about their study. Then, if that person encounters the virus naturally, their immune system could process it as a second infection that’s much more severe.

Takeda is aiming to circumvent that problem. “An ideal vaccine would have an acceptable safety profile and protect against all four types of the virus in both adults and children, whether or not they have been previously infected with dengue,” Duke-NUS Medical School professor emeritus Duane Gubler said in the Japanese company's study announcement.

According to the WHO, 40% of the world's population lives under the threat of dengue, meaning dengue vaccines have a huge potential for sales by volume, even though many of the people at risk live in developing countries with limited healthcare budgets. To address this, Sanofi said early on it was "flipping the model" with its Dengvaxia launch, favoring wide access in highly endemic, middle-income countries rather than first going to Europe and the U.S.

Takeda’s Phase III dengue push follows a $312 million Zika vaccine deal struck last week with the U.S. government. The first tranche of funding will provide nearly $20 million for Takeda to complete preclinical work and vaccine development through Phase I. Big Pharma rivals GlaxoSmithKline and Sanofi have each signed on with U.S. government entities to advance their own Zika prospects.

In dengue, Takeda trails Sanofi, which spent 20 years and $1.5 billion to blaze a path to market for the three-dose Dengvaxia. The vaccine's launch has been slower than expected, however; Sanofi said in July that Dengvaxia would miss its 2016 sales estimate of €200 million. In the second quarter, the vaccine turned in just €1 million in sales, and Sanofi has attributed some of the struggles to political and economic turmoil in Latin America.

Vaccination campaigns are seen as a key part of Dengvaxia's launch, and so far, the Philippines and Brazil’s Paraná state have unveiled large-scale efforts.

Also in Phase III testing in Brazil is a dengue vaccine candidate developed by the U.S. National Institutes of Health.

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