FDA says it will consider approval of first dengue vaccine, despite controversy

The Food and Drug Administration has agreed to consider Sanofi Pasteur’s application for Dengvaxia, the world’s first licensed vaccine that protects against dengue but one that brings with it considerable controversy and concern.

The company announced Tuesday that it has received notice the regulatory agency will give the vaccine’s file a priority review, which means a decision must be rendered within six months.

While occasional cases have been diagnosed on the U.S. mainland, the real burden of dengue in the United States is in Puerto Rico, the U.S. Virgin Islands, Guam, and some other offshore territories.

“We’re excited because we want to bring this vaccine to the endemic areas like Puerto Rico and the U.S. territories where dengue is a severe disease and causes thousands of cases, some of which are very severe and lead to hospitalizations and unfortunately even some deaths,” Dr. David Greenberg, Sanofi’s regional medical head for North America, told STAT.

The global impact of dengue is massive — 400 million infections a year — and it has long been a public health dream that a safe and effective dengue vaccine would substantially lessen the disease’s toll on people and on health care systems that are deluged during dengue epidemics.

There are four serotypes of dengue, numbered 1 through 4. Infection with one does not protect against the others. In fact, the risk of having severe dengue is highest during a person’s second dengue infection, a phenomenon called antibody-dependent enhancement, or ADE.

Dengvaxia, which targets all four strains, is the first dengue vaccine that has come through the development pipeline. It is currently licensed in 20 countries, though to this point it is only available in 10.

In mid-October, a committee of the European Medicines Agency recommended granting marketing authorization for Dengvaxia for people who are between the ages of 9 and 45, who live in an area where dengue is endemic, and who have already had at least one prior dengue infection.

Despite excitement over the availability of a dengue vaccine, Dengvaxia is seen by some as troubled.

Late last November, Sanofi reported that post-marketing research had showed something that a number of dengue experts had long feared: The vaccine appeared to raise the risk of severe disease in children who were vaccinated before they’d had a dengue infection.

That led to a loud outcry in the Philippines, which was the only country to that point to roll out the vaccine in large-scale campaigns. Use of the vaccine there has been suspended, and confidence in vaccines as a whole has plummeted.

The Sanofi data — from clinical trials used to bring the vaccine to market — showed that children who had been vaccinated after at least one dengue infection were protected by the vaccine. In that group, the vaccine lowered the risk of hospitalization for severe dengue infection, which can be fatal.

But the story was different for children who had never contracted dengue before they were vaccinated. In those kids, the vaccine acted like a first infection. And if they later contracted dengue, they were more likely to have severe disease.

In the face of the new data, an expert panel that advises the World Health Organization on vaccines recommended that the vaccine should only be given to people who are known to have had a previous infection.

That effectively closed the door for Dengvaxia to be marketed widely as a travel vaccine, cutting out a lucrative market for a vaccine of this type.

Many people who contract dengue experience only mild symptoms that could be mistaken for influenza or another illness. Even more have no symptoms at all. That means in countries where dengue infections are common, many people won’t have a medical record proving they’ve been infected and won’t know with certainty what their dengue status is.

That means in many cases people will need to be tested before they are vaccinated. Currently there is no rapid test that could allow doctors to test and then vaccinate in the same office visit. Sanofi has been working with other companies to spur develop of rapid point-of-care tests, but there is no estimate at the moment of how soon they will be developed, tested, and approved for use, Greenberg said.

Greenberg suggested that in Puerto Rico, the vaccine — if approved — could be used by people who had a medical record showing a confirmed dengue infection or in a two-step process where drawn blood would be tested by a commercial laboratory. People who had dengue antibodies could return to their physician to be vaccinated.

Sanofi will not disclose sales projections for the vaccine, but Greenberg insisted the company’s motivation is the public health benefit the vaccine can offer. “We want to protect as many people as we can,” he said.