FOCUS-Not discouraged by the fall of Sanofi, Takeda takes the same path with dengue shooting

CHICAGO, Jan. 30 (Reuters) – A new dengue virus vaccine is taking a potentially risky route to preventing mosquito-borne disease, which affects nearly 400 million people each year.

Takeda Pharmaceutical Co Ltd plans to seek the approval of the experimental vaccine first in countries where the virus is endemic, rather than starting with the United States or Europe, whose rigorous reviews are often used as a reference throughout the world, said company executives in Reuters.

This strategy is similar to that used by Sanofi SA, which licensed the world's first dengue vaccine, Dengvaxia, in endemic markets in 2015 before seeking approval from Western regulators. annual sales of $ 1 billion.

But the drug maker has failed to reach this target. At the end of 2017, Sanofi revealed that dengvaxia could increase the risk of severe dengue in children who have never been exposed to the virus, triggering a government investigation in the Philippines where 800,000 children of childbearing age have been exposed. to attend school had already been vaccinated.

The impact of Sanofi's vaccine raised the bar to demonstrate the safety of future dengue vaccines.

Takeda officials expect a different result, hoping that their approach will prevent the setbacks suffered by Sanofi.

On Tuesday, Takeda said his vaccine was effective in preventing all four types of dengue, thus reaching the primary goal of his terminal clinical trial. The company said that no major safety issues had emerged, giving hope that this would be the next viable vaccine against the tropical virus that kills up to 25,000 people each year.

Takeda will first seek approval in each of the eight countries where his clinical trial took place: Brazil, Colombia, Panama, Dominican Republic, Nicaragua, Philippines, Thailand and Sri Lanka.

"We still expect dengue vaccines to be the most important," said Derek Wallace, head of Takeda's global dengue vaccine program, in countries where dengue fever is endemic.

FUTURE VACCINE

The success of TAK-003 is crucial to Takeda's vaccine ambitions, with the Japan-based drug maker integrating its $ 59 billion purchase of Shire Plc.

"Global activity was based on global products and a global pipeline," said Dr. Rajeev Venkayya, president of Takeda's vaccine division, in a phone interview.

Under pressure to cut costs after the agreement with Shire, Takeda needs a strong performance from its experimental dengue and norovirus vaccines to prove the viability of global vaccine business.

"Once these two programs are declared, we will define the future of our future," Takeda Research Director Andy Plump said last month. Venkayya is said to be encouraged by the results achieved so far.

Dengue experts wondered if Takeda's vaccine could pose similar risks to dengvax, and the results released on Tuesday were not detailed enough to provide answers.

Takeda officials said they took steps to make sure their vaccine did not have the same problems.

Takeda's TAK-003 is based on a dengue 2 virus, with genes from the other three other dengue viruses added. Dengvaxia is based on a yellow fever virus containing dengue genes. reply.

Unlike Sanofi, Takeda researchers took blood samples from the 20,000 trial participants before receiving the vaccine. This should allow them to see differences in vaccine performance among people who have already had dengue infection compared to others, according to experts.

Takeda delayed the publication of his trial results for several weeks to characterize the immune response of all participants. The company expects some of these data to be published soon in a peer-reviewed medical journal.

REGRET OF SANOFI

Earlier this month, David Loew, head of vaccines at Sanofi, told FiercePharma that the company regretted having launched Dengvaxia in emerging markets before its review by the US Food and Drug Administration or the European Medicines Agency . This is the first time that Sanofi has adopted such an approach with a vaccine, he said.

"Other regulators often turn to the FDA and the EMA for their own guidelines," Loew told Reuters via email.

To share its data with endemic countries and answer questions about dengvaxie, Sanofi participated in a three-day meeting organized by the World Health Organization and the Vaccination Initiative against dengue in July 2015. Regulators from seven countries where dengue is the biggest threat, including the Philippines, were there.

Dengvaxia has since been approved in Europe for people living in endemic areas with documented previous infection. The vaccine is also under review by the FDA.

Dr. Joachim Hombach, Senior Health Advisor, WHO Vaccine Department, said the governments of Latin American countries and dengue fever where dengue fever is endemic are now "very aware" of the potential risks of malaria. dengvaxie.

"We will look at this very carefully," Hombach said of Takeda's data.

Takeda is not discouraged.

The company plans to file in the US and Europe one year after filing in dengue-endemic countries, said Venkayya. Takeda and dengue experts are already considering ways to review the latest vaccine data with these regulators.

The Global Consortium for Dengue and Aedes-transmitted Diseases (GDAC), funded in part by drug manufacturers and working closely with the WHO, has scheduled a meeting in early March in Bangkok with regulators from at least six countries to review Takeda's findings, said Dr. In-Kyu Yoon, Director of GDAC.

Yoon said the meeting would be funded by the International Vaccines Institute, funded largely by charities and the Korean government. It is considering asking countries for a joint regulatory review similar to that in which Sanofi participated in 2015.

"Right now, there is clearly some caution," Yoon said.