After safety mess, Sanofi's dengue shot nabs a sharply limited FDA nod

Sanofi Pasteur HQ
The FDA has approved Sanofi's controversial dengue vaccine Dengvaxia with major limitations to its use. (Sanofi/Vincent Moncorgé)

Sanofi’s controversial dengue vaccine Dengvaxia has finally snagged a U.S. green light. But the limitations the FDA slapped on its label could seriously dent its uptake and officially put its previous blockbuster expectation to rest.

While Sanofi Pasteur had sought approval in people aged 9 to 45—the same population cleared by European regulators—the FDA handed the nod in the 9- to 16-year-old age group.

And as expected, Dengvaxia is only allowed in children who've been infected with dengue before and who live in endemic areas. In the U.S., that means just Puerto Rico, the U.S. Virgin Islands, American Samoa and Guam, according to the Centers for Disease Control and Prevention and the FDA. On a positive note, though, Sanofi got a priority review voucher for developing a tropical disease drug.

In a statement to FiercePharma, a Sanofi spokesman said it’s “premature to speculate on any market impact the revised indication may have.” Sanofi will work with payers and public health officials to determine the price for the vaccine, he said. The company is also working on a point-of-care diagnostic to identify children with prior dengue infections.

The FDA’s decision follows recommendations from an advisory panel in March. Experts on the FDA’s vaccines committee evenly split on Dengvaxia’s safety in people 9 to 45 years old, and decided against its effectiveness in the broad age group by 7-6 with one abstention. In the 9-to-16 age group, the panel voted 13-1 in favor of efficacy and 10-4 on safety.

The age distinction likely stems directly from the data Sanofi accumulated on the shot. According to briefing documents for the panel, Dengvaxia has efficacy data in 9- to 16-year-olds; it's shown an actual reduction in the number of confirmed dengue episodes in that age group. Among the three clinical trials involving about 35,000 individuals in this age group in dengue-endemic areas, the vaccine was found to be 76% effective in preventing dengue disease, according to the FDA.

RELATED: After Philippines safety scandal, Sanofi's Dengvaxia set for European approval

But in older patients, Dengvaxia only has immunogenicity data. Dengvaxia did show it could increase serotype-specific neutralizing antibody levels in those people. But exactly how that translates into clinical effectiveness isn't clear.

“The FDA requested additional data in people 17 through 45 years of age, particularly in countries where the dengue burden is lower, to supplement our bridging data,” the Sanofi spokesman said. “We are open to evaluating additional opportunities to expand Dengvaxia’s indication as new clinical and epidemiological data becomes available.”

Dengvaxia, the first dengue vaccine, sparked controversy in late 2017 when Sanofi unveiled new data showing that, instead of protecting all people from dengue episodes, it actually increased the risk of severe dengue in children who had never been infected before.

The Philippines, a dengue-endemic country that had launched a national Dengvaxia immunization program, demanded refunds from Sanofi and revoked its approval for the vaccine. In March, the country’s prosecutors said they had found probable cause to indict Sanofi and government officials for the deaths of 10 children allegedly linked to Dengvaxia.

RELATED: Takeda’s dengue shot, rival to Sanofi's Dengvaxia, hits the mark in massive phase 3 study

In response to the new safety data, the World Health Organization advised against using Dengvaxia in people without a proven history of dengue infection. Recent approvals by the European Commission and now the FDA have followed that advice.

Problem is, determining previous exposure is tough. Other than medical records of lab-confirmed cases, the FDA expert panel noted that currently available serological tests may lead to false positive results because of cross-reactivity with other flaviviruses.

Sanofi Pasteur is currently working with a diagnostics maker to co-develop a point-of-care, rapid diagnostic test designed specifically to detect prior dengue infections, the company spokesman told FiercePharma. The pair now looks to begin the registration of the optimized test from late 2020 onward, he said.

Dengvaxia could soon face competition from Takeda’s prospective dengue shot TAK-003. In January, the Japanese pharma said the experimental vaccine has cleared a large phase 3 in children aged 4 to 16 regardless of previous infection history.