How Takeda developed its dengue vaccine after decades of setbacks

How Takeda developed its dengue vaccine after decades of setbacks

Kanoko MatsuyamaBloomberg

06 November, 2022, 11:35 am

Last modified: November 06, 2022, 11:50 am

Dengue patients in Pakistan. The illness can be so severe that it is also known as “breakbone fever.” Photo: Bloomberg

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Dengue patients in Pakistan.  The disease can be so severe that it is also known as

Dengue patients in Pakistan. The illness can be so severe that it is also known as “breakbone fever.” Photo: Bloomberg

After decades of delays, the first dengue vaccine was introduced seven years ago. But that formula, from Sanofi, was soon found to be suitable only for people who had previously been infected with the disease, prompting researchers at Japan’s Takeda Pharmaceutical Co. to redouble efforts on an alternative. That work is finally paying off, with its version expected to hit the market early next year.

Dengue infections have increased eightfold in the last two decades, to almost 400 million a year, according to researchers at the University of Oxford. About half the world’s population already lives in areas threatened by dengue, and scientists warn that climate change is likely to accelerate the spread of the mosquitoes that carry the virus. Since 2013, the US has seen outbreaks in Florida, Hawaii and Texas. Europe saw local transmission in France and Croatia in 2010, and a 2012 outbreak on the Portuguese island of Madeira resulted in more than 2,000 cases.

Infographic: Bloomberg

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Infographic: Bloomberg

Infographic: Bloomberg

Although most cases of dengue fever are mild and usually cause flu-like symptoms, some infected people experience a sudden onset of fever, headache, skin rashes, and muscle pain so severe that some call the illness “high fever.” breaks bones”. Half a million dengue patients a year require hospitalization for complications that can result in shock and internal bleeding. Some 20,000 die, mainly children.

Indonesia approved Takeda’s Qdenga in August and the company says it will start selling it there early next year. In October, a European Union advisory panel said that Qdenga can be given to people as young as 4 years old, a recommendation that could lead to EU consent within a few months. And the company is seeking approvals in about a dozen other countries, including the US.

Qdenga highlights the growing successes in the fight against mosquito-borne diseases. The first malaria vaccine, developed by GSK Plc and its partners, was backed by the World Health Organization last year, enabling purchases from governments and international organisations. Another Oxford University vaccine has shown that its protection can last for a year after a booster. And Takeda says he is planning mid-term trials of a Zika vaccine.

Sanofi began work on its vaccine in 1997 and obtained Mexican approval for what it called Dengvaxia in 2015. The vaccine was soon introduced in 19 countries, but an analysis of clinical data in 2017 showed that for people receiving Dengvaxia who had never had dengue, the drug increased the risk of developing serious illness if they later became infected.

Takeda’s path to Qdenga began in 2013 when it bought Inviragen Inc., a company in Colorado that had been working on the vaccine. Testing its efficacy and safety was complicated because dengue can be caused by four different strains, and protection against all of them must be built. In some cases, patients who are reinfected with a different strain may experience more severe symptoms because neutralizing antibodies generated by the first infection can bind to the virus and increase its ability to enter cells. Although unclear, some researchers say a similar pattern may occur in vaccinated people, possibly the main cause of Dengvaxia’s difficulties.

To make sure its vaccine didn’t encounter similar problems, Takeda conducted more than four years of follow-up studies. The more than 1 million pages of data he sent to European authorities looked at people who had been infected before, as well as those who had never had dengue, something previous vaccines did not do. “We learned from failure,” says Christophe Weber, CEO of Takeda. “We designed the trial to specifically answer this question. That’s what gives us confidence.”

Takeda’s two-shot immunization is based on what is called the serotype 2 variant, with components from the other three strains attached. In a trial involving 1,800 young people from the Dominican Republic, Panama and the Philippines, the drug induced an immune response against all four strains that lasted at least four years after injections.

That result allowed Takeda to move on to a test that involved more than 20,000 participants in Asia and Latin America. The vaccine reduced recipients’ hospitalizations by 84% compared to placebo and prevented illness by 61%, with no significant safety risks. Although the vaccine is not equally effective against all four strains, says Weber, “the important thing is to look at overall efficacy.”

Qdenga’s strength is that it was based on a dengue virus, while Dengvaxia based its version on yellow fever, says Cameron Simmons, director of the Institute for Vector-Borne Diseases at Monash University in Australia. “It’s more like dengue,” he says. “So you’re presenting more dengue virus antigens, so to speak, to the immune system.”

Duane Gubler, a professor emeritus at the Duke-NUS School of Medicine in Singapore and part of a team that worked on the vaccine at the US Centers for Disease Control and Prevention, tracked recipients. “I don’t think it’s been proven effective against dengue 3 and 4 because we haven’t had a lot of dengue 3 and 4 activity,” says Gubler. “We have to wait for that.”

After decades of delays, the first dengue vaccine was introduced seven years ago. But that formula, from Sanofi, was soon found to be suitable only for people who had previously been infected with the disease, prompting researchers at Japan’s Takeda Pharmaceutical Co. to redouble efforts on an alternative. That work is finally paying off, with its version expected to hit the market early next year.

Dengue infections have increased eightfold in the last two decades, to almost 400 million a year, according to researchers at the University of Oxford. About half the world’s population already lives in areas threatened by dengue, and scientists warn that climate change is likely to accelerate the spread of the mosquitoes that carry the virus. Since 2013, the US has seen outbreaks in Florida, Hawaii and Texas. Europe saw local transmission in France and Croatia in 2010, and a 2012 outbreak on the Portuguese island of Madeira resulted in more than 2,000 cases.


Disclaimer: This article first appeared on Bloomberg and is published through a special syndication agreement.

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