Sanofi scandal in the Philippines could spread dangerous mistrust of vaccines

In an era when too many people remain suspicious of vaccines, one of the world’s largest manufacturers may have made matters worse while trying to eradicate dengue fever.

For the past two weeks, Sanofi has been engulfed by scandal in the Philippines after disclosing that its Dengvaxia vaccine could worsen — rather than prevent — future cases of the mosquito-borne virus in people who had not previously been infected. About 830,000 children in the Philippines were vaccinated; now the government is demanding a $59 million refund and probing whether the vaccine was approved improperly.

Unfortunately, there are indications that the company, which could use a blockbuster product, should have taken its corporate foot off the gas pedal.

And to restore confidence in vaccines, a reckoning is required.

“At a time when convincing people to be vaccinated has encountered increasing resistance, it’s really unfortunate to have this story emerge,” said Glenn Cohen, a Harvard Law School professor who is an expert in health law and bioethics. “The company owes a full accounting of what it knew and when.”

Read more: Scientists solve a dengue mystery: Why second infection is worse than first

To be fair, vaccine development is riddled with unforeseen complications. And Sanofi deserves credit for investing $1.5 billion over 20 years in a product designed to combat a virus that can be deadly. Just two years ago, dengue struck more than 3.2 million people in Asia and the Americas.

With that said, Sanofi could have done certain things differently.

For starters, although the company ran two trials involving more than 31,000 people, it only looked at a small subset of about 10 percent of these participants to gauge how the vaccine affected those who never had dengue fever.

A Sanofi spokesman explained that the company didn’t anticipate differing reactions depending on patient infection histories and considered it unethical to sample blood from everyone. And it was only more recently that Sanofi was able to develop an assay to sort out the impact of previous infection, the spokesman explained.

But not everyone agrees the initial approach taken by Sanofi was correct.

In retrospect, “it would have been perfectly reasonable to test everybody at the time of the study,” said Joachim Hombach, a World Health Organization senior health advisor for immunization policy. “There were some things in the clinical development program that could have been done differently to generate data to have a better understanding of exactly how the vaccine performs in different population groups.”

Sanofi’s interpretation of the clinical trial data has also caused second guessing.

The studies found a high hospitalization rate in younger children who were vaccinated. Sanofi responded by creating a cut-off: The company decided not to pursue vaccination for anyone younger than nine. The thinking was that older children were more likely to have been exposed to dengue and so would be less likely to develop a reaction to the vaccine. A Sanofi spokesman noted that this decision was explained in the company’s analysis of the trial data, which was published in the New England Journal of Medicine in 2015.

But rather than be accepted as innocuous fact, the adverse reactions among young patients should have been a warning signal, according to Dr. Scott Halstead, a former U.S. Army scientist who first flagged problems with the vaccine.

“As somebody who has been studying this for years and years, [Sanofi’s] hypothesis did not have any integrity,” he argued. “Nobody can say a two- or five-year-old has an immature immune system. We vaccinate children from birth all the time and depend on their immune systems to be competent.”

For its part, the WHO stated last year that vaccination “may be ineffective or may, theoretically, even increase the future risk of hospitalized or severe dengue illness” in anyone who was never previously infected at the time of first vaccination, regardless of age. And a pair of scientific papers published over the past two years also suggested such a problem with the vaccine.

Yet Sanofi proceeded to work with governments that vaccinated many people who had never been exposed to dengue — as long as they were older than nine.

Read more: Cheap, fast test for Zika and dengue could cost just $1

Of course, hindsight is, as they say, a wonderful thing.

But this episode does raise the question of whether the company moved too quickly because it needed a big seller.

The company’s key diabetes franchise, which accounted for 25 percent of its pharmaceutical sales last year, has been struggling. Dengvaxia, which has not yet been approved in the U.S., was forecast to generate $840 million in annual sales by 2020. That’s not enough to compensate for its larger strategic problems, but any notable contribution to the bottom line would have helped.

Instead, Sanofi is taking a $120 million charge against earnings this quarter.

Meanwhile, the company is about to become ensnared in an ugly probe in the Philippines, where lawmakers want to know why the government paid for the vaccine despite the safety questions. Local officials have also fined the company for advertising its vaccine, because marketing prescription medicines to consumers is prohibited in the Philippines.

Where the investigation will lead is unclear, but Sanofi needs to come to grips with this episode. Otherwise, we run the risk that too many people will end up being inoculated with baseless mistrust of vaccines.