Early data on Takeda's dengue vaccine is promising, but wait for the full dataset
Takeda’s answer to Sanofi’s controversial dengue vaccine is here. The Japanese drugmaker, which is hoping to avert the challenges faced by its French rival to develop a product for the mosquito-borne disease, broke out the numbers from the first tranche of its pivotal trial on Wednesday.
The placebo-controlled trial, called TIDES, is testing the impact of two doses of the vaccine — TAK-003 — in preventing dengue fever, triggered by any of the four viral strains, in more than 19,000 patients aged four to 16 years in parts of Latin America and Asia where the disease is endemic.
The vaccine’s efficacy, on average, hit 80.2% — meeting the primary endpoint of the first part of the trial. The subjects were given the two doses three months apart — the main goal was assessed 15 months after the first dose (12 months after the second dose).
Efficacy for serotype 2 registered at a splendid 97.7% — but serotype 1 came in at 73.7% and serotype 3 was even worse at 62.6%. There were not enough cases of serotype 4 for assessment, Takeda said, adding that the percentage of participants with serious adverse events was similar across both the drug and placebo arms.
“These results support a potential benefit regardless of previous dengue exposure or age, and the onset of some protection after the first dose suggests that the vaccine may be useful in the context of outbreak control or travel vaccination; however, reported variation in serotype-specific efficacy needs careful consideration,” researchers wrote in a report about the trial in the New England Journal of Medicine.
The second portion of the study will track participants for another six months, while the third and final portion of the study will trail patients for an additional three years. Meanwhile, Takeda is fortifying its manufacturing apparatus in advance of the vaccine’s approval — it has just also christened a €130 million plant in Germany.
Takeda is hoping its effort will not crash and burn like Sanofi, which once harbored blockbuster expectations for Dengvaxia, the world’s first dengue vaccine. That dream was shattered after the French group was forced to concede in late 2017 that vaccine could enhance the risk of severe dengue in children who had never been exposed to the virus — only after the Philippines used $70 million worth of the shot in a mass vaccination campaign for 800,000 children.
In May, the US health regulator sanctioned the use of Dengvaxia as the first-ever product to prevent the mosquito-borne disease in children who have previously contracted dengue and who live in areas rife with the disease. The vaccine — which is administered as three separate injections — was found to be roughly 76% effective in preventing symptomatic dengue disease in individuals 9 through 16 years of age who previously had laboratory-confirmed dengue disease, the FDA noted. But in the United States and its territories, no available tests have been cleared by the FDA to determine a previous dengue infection, Sanofi has acknowledged.
Even before the Philippines’ public health crisis, experts had warned that vaccination with Dengvaxia in those who had not already been infected by one of the four different serotypes of the virus faced a potentially life-threatening fever upon subsequent infection. This is because their bodies would likely treat the first real dengue infection as their second, thanks to the vaccine. According to the FDA, roughly 95% of all severe/hospitalized cases of dengue are associated with second dengue virus infection.
The dengue virus is widespread across the tropics. Severe dengue was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand, currently affecting most Asian and Latin American countries, and is considered a leading cause of hospitalization and death among children and adults in these regions, according to the WHO. The CDC estimates that each year, about 400 million dengue virus infections occur globally. The dengue virus is carried by female Aedes aegypti mosquitoes (and to a lesser extent, Ae. albopictus) — the same species that also transmits chikungunya, yellow fever and Zika.