Sanofi ordered to pull Dengvaxia in Philippines as safety episode escalates

The Philippines' FDA ordered Sanofi to remove Dengvaxia from the market on Monday. Pictured is a dengue prevention worker spraying mosquito repellent in Bangkok in June 2012. (Sanofi Pasteur/Patrick de Noirmont)

Sanofi's Dengvaxia problem in the Philippines has gone from bad to worse. After suspending a school-based immunization campaign on safety concerns, the country has ordered the drug giant to withdraw the world's first dengue vaccine from the market. 

In a Monday advisory, the Philippines' FDA wrote that it directed Sanofi to "suspend the sale/distribution/marketing of Dengvaxia and cause the withdrawal of Dengvaxia in the market pending compliance with the directives of the FDA." 

A Sanofi spokesperson told FiercePharma the company has been "informed of the position of the Philippine Food and Drug Administration ... and will work with them to review the implementation of their direction. We will continue to seek constructive and transparent dialogue with them." 

The order comes right after Sanofi issued an advisory about the risks of the shot in recipients with no prior dengue infection. In those patients, the shot can cause more serious dengue infections. To get the word out, the regulators in the Philippines also ordered Sanofi to "conduct an information dissemination campaign," with public advisories and communications with doctors and patients. 

RELATED: Sanofi's Dengvaxia scrutiny mounts as Philippines slams brakes on dengue shots 

Based on data at hand, Sanofi estimated 1 in 800 dengue infections would be severe among unvaccinated people. In the new analysis of a five-year follow-up study, the increased risk translated to two more cases of "severe dengue" per 1,000 people who had not been exposed to the virus, the company's spokesperson told FiercePharma. All recovered with treatment. 

Before the advisory, more than 700,000 school-age children had received their first vaccinations in the Philippines as part of the government's campaign. But the country quickly responded to the warning, shutting down that effort—one of two public Dengvaxia campaigns that has ever been conducted around the world—and starting an investigation. 

The World Health Organization reacted swiftly as well. The agency published a notice that it's conducting a "full review" on Dengvaxia and will issue "revised guidance" for its use. WHO originally recommended the vaccine for use in areas with high dengue incidence. 

In the meantime, WHO "recommends that Dengvaxia is only administered to subjects that are known to have been infected with dengue prior to vaccination." 

Sanofi's advisory wasn't the first time a potential issue with the vaccine has come up. Last year, a team at Imperial College London highlighted the same dynamic in a study, noting that the vaccine "acts very much like a natural infection but without making recipients sick." 

Afterward, if a vaccinated person then encounters the virus naturally, their immune system could process it as a second infection that's much more severe, according to the researchers.

In an interview at the time, Sanofi Pasteur’s director of global medical affairs for dengue, Dr. Cesar Mascareñas, told FiercePharma the study didn’t change Sanofi’s expectations or strategies for Dengvaxia because it was only a “mathematical model” and not “evidence-based.”

Additionally, he said, it was one of eight models considered by the WHO in making its initial recommendation that the vaccine be used in countries where the virus is more than 50% prevalent. 

"It’s not new information for the experts," he said at the time. "It has been taken into account by the experts at the WHO." 

Mascareñas said key to the Dengvaxia launch would be government immunization campaigns in Mexico, which seriously considered such a program, and throughout Latin America and Asia. But nearly two years after Mexico's approval, the Philippines and Brazil remain the only two countries to have introduced the shot in government campaigns, according to the WHO.

After originally carrying blockbuster sales expectations, Dengvaxia has come far short of projections, reeling in just 22 million ($26 million) so far this year.

Editor's note: An earlier version of this story stated that the Philippines was the only country conducting a large immunization campaign with Dengvaxia. Brazil's Paraná state is still using the vaccine.