Takeda’s Dengue Vaccine Shows Promise

Scientists are making progress in developing new weapons against dengue, a debilitating mosquito-borne virus that threatens half the world’s population. Takeda Pharmaceutical Co. released data from a sizeable late-stage study Saturday showing that its experimental dengue vaccine was highly effective in preventing children from dengue illnesses and hospitalization overall from four types of the virus. But the results suggested one potential concern, and the vaccine was slightly less effective overall than earlier data showed.

Effective measures to stop the spread of dengue are among the most urgent needs in global public health. Approximately 3.9 billion people in tropical regions of the world are at risk of infection with the virus, which is carried by an aggressive mosquito that teems in populated areas. An estimated 390 million people a year are infected with dengue. The World Health Organization listed dengue among ten global health threats of concern in 2019. But only one licensed vaccine—Dengvaxia from Sanofi SA, is available so far, and it has had safety problems. Takeda’s ongoing clinical trial of its TAK-003 vaccine, involving approximately 20,000 children between the ages of 4 and 16 years in eight countries, is being closely watched.

Takeda said Saturday that its vaccine reduced the risk of dengue illnesses in children by 73.3% 18 months after receiving their second dose. The vaccine also reduced by 90.4% the risk of dengue illnesses requiring hospitalization. “We think this data is very, very exciting for the entire public-health community,” said Rajeev Venkayya, President of Takeda’s Global Vaccine Business Unit. The Tokyo-based company released its results at the annual meeting of the American Society of Tropical Medicine and Hygiene, in National Harbor, Md. The vaccine’s efficacy at 18 months was lower than the 80.2% it showed at 12 months, however. The 12-month data were published in the New England Journal of Medicine earlier this month. The change was due to the types of dengue causing illness in those respective time periods, and a lack of efficacy involving one virus type, the company said.

There are four types of dengue, and a person can be infected more than once. Secondary infection is often more severe than the first. An effective vaccine, therefore, must protect both people who have and haven’t been infected before. Takeda’s results signalled a concern with protection from “serotype 3” dengue in children who hadn’t been infected previously with dengue. The findings show they were slightly more likely to develop a fever from that serotype. Takeda said the finding is statistically inconclusive, but that it suggests a lack of efficacy in that situation. “At the moment, it’s not conclusive and something we will have to watch over time clearly,” said Derek Wallace, Takeda’s Global Dengue Program Head.

The finding with serotype 3 in children who are “seronaive,” or haven’t been infected before, is concerning because it is reminiscent of Sanofi’s safety problem with Dengvaxia, said Anna Durbin, a professor at the Johns Hopkins Bloomberg School of Public Health. She has worked on another dengue vaccine candidate made by the U.S. National Institute of Allergy and Infectious Diseases. “The lack of efficacy to DENV-3 in seronaives is worrisome,” she said. Still, she said of the vaccine, “Overall, the efficacy is very good and higher than that seen with Dengvaxia, which is encouraging.” Sanofi disclosed in 2017 that Dengvaxia could in some cases, mimic an initial dengue infection. Dozens of children who were immunized in the Philippines fell ill, with some hospitalizations and deaths. The WHO and Sanofi recommend against giving Dengvaxia to people who haven’t been infected with dengue previously. A Sanofi spokeswoman said no causal link had been established between the vaccine and long-term health effects, including death.

Takeda’s finding is different from Sanofi’s experience with Dengvaxia, a differently constructed vaccine, Dr Wallace said. While children who hadn’t been infected before were slightly more likely to develop a fever related to serotype 3, they were not more likely to be hospitalized or to have severe dengue, he said. Moreover, Takeda’s vaccine reduced the risk of dengue overall for both people who have and haven’t been infected before, he said. The company plans to follow trial participants for a total of 4.5 years, Dr Wallace said. Takeda will release 24-month vaccine efficacy results in the first half of 2020, he said. The company plans to file for regulatory approval with the European Medicines Agency starting in the second half of next year, working simultaneously with regulatory authorities in countries where the vaccine would be used.

In another approach to combat dengue, researchers at the same conference demonstrated sharp drops in illnesses in areas where they released mosquitoes bred in laboratories with bacteria called Wolbachia that prevent the spread of the virus. Transmission of dengue fell 76% over 27 months in a community in Indonesia after the lab-grown mosquitoes were released. Infections have also fallen sharply in communities in Brazil, Vietnam, and Australia, said Cameron Simmons, Director of Impact Assessment for the World Mosquito Program (WMP), which is running the projects in 12 countries. The WMP aims to release results in 2020 of a large randomized trial conducted in Indonesia, he said.

Credit: Betsy McKay for The Wall Street Journal, 23 November 2019.