Timeline: the dengue vaccine dilemma

In the spring of 2016, Dengvaxia had a high-profile launch in the Philippines, as the country – having been involved in every phase of clinical development – became the first in the world to access the live recombinant tetravalent vaccine. The Department of Health spent $67m on Dengvaxia and kicked off a mass immunisation programme with the aim of vaccinating a million students by the end of the year.

Sanofi also had high hopes for Dengvaxia, the development of which had taken 20 years and cost around $1.8bn. Officials predicted that the vaccine – which helps protect against all four serotypes of dengue – would drive down infection rates by 24% within the next five years, and Sanofi looked well-positioned to reap the benefits of offering the first-ever dengue vaccine to global markets. By October 2016, Dengvaxia had received regulatory approval from ten other countries, including Mexico, Brazil and Indonesia.

Elsewhere, Sanofi continued seeking regulatory approval for Dengvaxia for use in those who have already been exposed to dengue fever, and in December 2018, the European Commission granted marketing approval for the vaccine to be used in already-exposed individuals aged nine to 45 years and living in dengue-endemic regions.

“In some of the European overseas territories where dengue recurs regularly, people who have had a dengue infection previously are at risk of being infected with the virus again,” said Sanofi Pasteur’s head of global medical affairs Su-Peing Ng. “As the second infection with dengue tends to be more severe than the first, it is important to be able to offer these people a vaccine that could help protect them against subsequent dengue infections,” she said.

While Dengvaxia’s use was suspended after Sanofi’s update in November 2017, its long-term future was still in question until February this year, when the Philippines Food and Drug Administration permanently withdrew the vaccine’s licence; the regulator’s director general Nela Charade Puno said the decision had been made because Sanofi failed to comply with its post-marketing commitments.

Meanwhile, the Dengvaxia scandal had by this time become the subject of two congressional inquiries and a criminal investigation. In March, the Department of Justice said it had enough evidence to charge both staff of Sanofi and Philippine health officials, including former Health Minister Janette Garin. The department argued the named defendants had ignored “the identified risks and adverse effects of the vaccine” and were responsible for the subsequent deaths. While a panel of medical specialists are gathering information about the alleged link, to date no conclusive evidence has been presented that connects the deaths to Dengvaxia specifically.

There is currently nothing to suggest that Dengvaxia is linked in any way to the deaths that have been at the centre of the allegations, and the vaccine’s subsequent approval by European and American authorities validates Sanofi’s statements that it is effective and safe when administered correctly.

Nevertheless, the controversy in the Philippines raises troubling questions around the governance of this immunisation drive, and how, despite years of clinical studies, the vaccine was allowed to be administered to those who may have been harmed by it. Without rock-solid safety data and careful management, a vaccination campaign could easily be seen as an exploitative gamble with public safety.

“When you are the first in class, we’re the ones having to develop and understand the science as we go,” Sanofi’s Ng told Reuters in December 2017.