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Sanofi’s Experience With Dengvaxia May Speed Development of Zika Vaccine

Opinion

Xconomy Boston — 

Dengvaxia, the first licensed vaccine for dengue virus, has now been approved in 11 countries where dengue is endemic. But sales of the vaccine, which were initially projected to reach €200 million this year, barely reached €20 million in the first half of the year, with little sign of picking up.

Sanofi Pasteur, the group behind the vaccine, would have reason to be disappointed with these results, given that the company invested twenty years and €1.5 billion in its development. Only the Philippines and Paraná state in Brazil have purchased Dengvaxia for massive vaccination campaigns so far, while Sanofi is still appealing for approval in key markets, including India.

Yet the company is probably deriving some consolation for the commercial woes with Dengvaxia from the leg up the experience has given it with the development of a vaccine against Zika virus. Both dengue and Zika are flaviviruses that behave similarly in the lab and interact with the immune system in similar ways. What’s more, Sanofi enrolled over 30,000 subjects in Latin America and Southeast Asia in clinical trials for Dengvaxia and has developed relationships with key ministries of health—experiences that Sanofi executives hope will accelerate the research and development process for a Zika vaccine.

Sanofi has attributed weak Dengvaxia sales to political and economic “turmoil” in Latin America—which probably refers largely to the political corruption crisis in Brazil. The real reason for Dengvaxia’s mediocre sales, though, may have more to do with its shaky scientific merit. Overall, the vaccine has only about a 60 percent efficacy rate. Crucially, follow-up data showed that the vaccine actually put children aged 2-5, who are likely not to have been exposed previously to dengue virus, at a seven-fold higher risk of a severe dengue infection requiring hospitalization. César Mascareñas, head of dengue at Sanofi, called this relative risk “huge” but emphasized that no such risk was seen in subjects over age nine, the group that Sanofi plans to target for vaccination.

Still, the nine year age cut-off is arbitrary and is likely just a surrogate for whether the subject has previously been infected with dengue virus. In unexposed people, some have hypothesized, Dengvaxia acts as a first exposure, allowing a subsequent dengue infection to behave more aggressively by harnessing the human immune system to spread the virus more effectively. So, limiting the vaccination to people over age nine will likely not guarantee protection from a more severe infection in all recipients. This uncertainty has probably led some ministries of health to question the wisdom of mass vaccination.

To its credit, Sanofi is conducting extensive surveillance of vaccinated subjects to monitor for any other safety issues. Even limiting vaccination to people over age nine, Sanofi can still hope to have a significant positive public health impact on this disease that infects over 3 million people each year. “We don’t have any treatment for the disease,” Mascareñas told me. “The vaccine should be put in this perspective.”

Unlike dengue, there is no evidence so far that a vaccine for Zika virus could place people at higher risk of severe infection. This should make development of a vaccine to Zika more straightforward.

Sanofi has partnered with Walter Reed Army Institute of Research (WRAIR) and the National Institutes of Health (NIH) to develop an inactivated vaccine to Zika virus.

Sanofi plans to start human trials on the vaccine this month, according to Jon Heinrichs, leader of the R&D effort for the Zika vaccine at Sanofi. In collaboration with WRAIR, NIH, and Beth Israel Deaconess Medical Center in Boston, Sanofi will conduct five concurrent phase 1 trials to assess the safety of the vaccine before moving toward larger phase 2 trials in 2017 that would take place in target populations, primarily in Latin America.

Heinrichs could not quote a firm timeline for development of the vaccine, but he did say that Sanofi’s experience with Dengvaxia is an important factor in allowing the company to move faster with Zika. “We have clinical sites in regions of the world where dengue was circulating, which happen to be some of the same places where Zika is being transmitted. We have relationships with ministries of health in regions where dengue exists,” Heinrichs told me.

With a couple dozen Zika vaccines in development, Sanofi’s laboratory and clinical trial experience with Dengvaxia could be a key head start in getting a vaccine approved.

While Heinrichs insists that Sanofi did not pursue a Zika vaccine because of commercial opportunity, sales could be significant, especially if a vaccine gains approval in the United States for travelers. If Dengvaxia sales do not pick up in 2017, eventual Zika vaccine sales could still represent a healthy return on Sanofi’s investment.