SNY Sanofi

By Betsy McKay in Atlanta, Preetika Rana in Hong Kong and Noemie Bisserbe in Paris 

Sanofi SA's recent disclosure of safety problems with the world's only approved vaccine against the viral infection dengue has complicated efforts to contain a growing global epidemic and could delay potential new vaccines, public-health experts said.

Late last year, the French pharmaceutical giant said its Dengvaxia product, first approved for sale in 2015, could in some cases worsen rather than prevent symptoms of the debilitating tropical disease. It was a frightening finding, and a setback for scientists who have spent decades and hundreds of millions of dollars trying to develop an immunization against dengue, a mosquito-borne virus that each year infects an estimated 390 million people in tropical regions world-wide.

Now, international health officials say Sanofi's troubles could fuel public distrust of vaccination and lead to regulatory or political hurdles that developers of new dengue vaccines such as Takeda Pharmaceutical Co., Merck & Co., and GlaxoSmithKline PLC must overcome, even though their vaccine candidates differ substantially from Sanofi's.

"There will be greater scrutiny now," said Joachim Hombach, executive secretary of the Strategic Advisory Group of Experts on Immunization, or SAGE, which advises the World Health Organization. Regulators, Dr. Hombach said, may require several additional years' worth of data on a vaccine's performance before allowing companies to market their dengue vaccines.

Lawmakers in the Philippines, where more than 800,000 children were vaccinated in a government-led immunization drive, have called for stricter reviews of drugs intended for mass use.

Future vaccine candidates will have to be tested carefully, Sanofi said. "Regarding the impact on other research efforts, we cannot know for sure, " a company spokesman said.

Of the people infected each year with dengue, about 96 million develop a flulike illness, sometimes called breakbone fever for the excruciating muscle and joint pain it can produce. About two million cases of dengue a year are severe, with internal bleeding or shock, and about 20,000 people die. Nearly four billion people--more than half of the world's population--are at risk of dengue infection.

The fallout from Dengvaxia "does impact, overall, the dengue field and the perception of dengue vaccines," said Rajeev Venkayya, who heads the vaccines business unit of Takeda, whose dengue vaccine is in a late-stage clinical trial involving more than 20,000 participants.

"We do not think this is going to be a showstopper in any way or form," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. He cautioned, however, that Sanofi's problems mean "clearly there's going to be not as smooth a trip." NIAID's dengue vaccine candidate is in a late-stage clinical trial involving 17,000 participants in Brazil.

"We should not give up on a dengue vaccine," Dr. Fauci said. "It's too important a disease." The NIAID vaccine has been licensed to several companies, including Merck, which said it plans to start its own trial this year.

Developing a vaccine is challenging: Four types of dengue virus can cause disease, and infection with one doesn't provide immunity to the others. Instead, an infection with one type increases the risk of severe dengue when someone is infected a second time, with a different type of the virus. Subsequent infections are less concerning because a person's immunity is broad by that point, scientists say.

Sanofi said in November that Dengvaxia could worsen symptoms in people who never had the disease. The vaccine, in effect, could mimic an initial infection in those people, increasing their risk of developing a severe form of dengue if they were infected later.

The government of the Philippines last month launched an investigation into its immunization program and Dengvaxia's possible link to the deaths of at least three children. The nation's health secretary said Thursday that regulators had temporarily suspended the vaccine's license and separately fined the company $2,000for failing to meet some post-marketing requirements.

Sanofi stopped producing Dengvaxia and said it would take a $119 million charge in the fourth quarter. The company said last month it would keep selling the vaccine, which it says is safe for people who had a prior dengue infection.

To avoid Sanofi's problem with its vaccine, new candidates must provide balanced protection against all dengue types, said Duane Gubler, chair of the Global Dengue and Aedes-Transmitted Diseases Consortium and an emeritus professor at Duke-NUS Medical School, who has consulted on dengue vaccines with Sanofi, Merck and Takeda.

NIAID's vaccine induced an immune response in tests against all four dengue types, individually and together, said Anna Durbin, a professor at the Johns Hopkins Bloomberg School of Public Health who led U.S.-based trials on the vaccine. Results from the clinical trial in Brazil could be available within the next year, Dr. Fauci said.

In studies, Takeda's dengue candidate demonstrated a "sustained antibody response" against all four dengue types in people regardless of previous dengue exposure, Dr. Venkayya said, adding results from its current trial are expected late this year.

Researchers drew pre-vaccination blood samples from all participants in late-stage trials of both vaccines, to determine whether they were infected with dengue before--a step Sanofi didn't take that made it difficult to pinpoint the problem with its vaccine.

GSK conducted an early-stage trial on one vaccine candidate, but now says it is trying "to identify the composition of a vaccine that could really induce a balance in response" against the four dengue types, though this work is at a "very early stage."

Write to Betsy McKay at betsy.mckay@wsj.com, Preetika Rana at preetika.rana@wsj.com and Noemie Bisserbe at noemie.bisserbe@wsj.com

(END) Dow Jones Newswires

January 07, 2018 08:14 ET (13:14 GMT)

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