Sanofi Pasteur’s controversial vaccine dengvaxia has been approved by the US Food & Drug Administration, the first dengue vaccine to get the regulatory nod in the US.
Dengvaxia ran into trouble two years ago when the Philippines had to suspend a school vaccination programme following several casualties. That is why the FDA has now cleared it for use only in people who have a previous history of the disease, particularly in dengue-endemic areas.
Dengvaxia is basically a live, attenuated dengue virus. An attenuated virus is a virus that retains its properties of triggering an immune response in the body but its ability to lead to a disease is compromised. Three dengvaxia shots are administered, with the second and third given six and 12 months after the first one. It was cleared in three randomised, placebo-controlled studies over approximately 35,000 individuals in dengue-endemic areas, including Puerto Rico, Latin America and the Asia Pacific region. It was found to be about 76% effective in 9-16-year-olds already exposed to the disease.
The need for a vaccine
According to the Centers for Disease Control and Prevention, an estimated 400 million dengue virus infections occur around the world. Of these, approximately 500,000 cases develop into dengue haemorrhagic fever, which contributes to about 20,000 deaths, primarily among children. In India, until November 26, 2018, 89,974 dengue cases were reported, with 144 deaths. In 2017 the counts were 1,88,401 and 325 respectively. India is among the dengue-endemic countries.
Dengvaxia is the first dengue vaccine to be licensed, Mexico being the first country to clear it in 2015. Subsequently it has been cleared in some 20 countries but what happened in 2017 in Philippines has raised question marks about CYD-TDV, as dengvaxia is known in technical parlance.
The Philippines casualties
Ten deaths were reported in the island nation in 2017 in the aftermath of a school vaccination campaign with dengvaxia. Some 800,000 school children had been vaccinated when adverse events started being reported and the campaign was suspended. Sanofi, in a statement soon afterwards, urged health authorities to update the product label. The statement said: “Based on up to six years of clinical data, the new analysis evaluated long-term safety and efficacy of Dengvaxia in people who had been infected with dengue prior to vaccination and those who had not. The analysis confirmed that Dengvaxia provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following vaccination upon a subsequent dengue infection.” In other words, Sanofi admitted the vaccine was not safe to be used in people with no history of the disease. WHO too issued a statement saying that it has asked the company for more data.
Earlier this year, Philippines permanently halted the sale distribution and marketing of dengvaxia.
The FDA recommendation
In its announcement last week, FDA said the vaccine can be used for the prevention of dengue “caused by all dengue virus serotypes (1, 2, 3 and 4) in people ages 9 through 16 who have laboratory-confirmed previous dengue infection and who live in endemic areas”.
“Dengvaxia is not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown. This is because in people who have not been infected with dengue virus, Dengvaxia appears to act like a first dengue infection – without actually infecting the person with wild-type dengue virus – such that a subsequent infection can result in severe dengue disease. Therefore, health care professionals should evaluate individuals for prior dengue infection to avoid vaccinating individuals who have not been previously infected by dengue virus,” the FDA said.
In May 2017, India turned down a recommendation of the Subject Expert Committee of the Drug Controller General of India and told Sanofi that there could not be a waiver of the requirement that a drug or vaccine, before being allowed to be marketed in India, would have to undergo phase III clinical trials (that establish safety and efficacy of a drug) on Indian subjects. “We were not convinced by the reasons given for waiver, nor did we think it prudent to go by the results of the phase III clinical trials done abroad. On hindsight, it was a good decision,” said a Health Ministry official. Sanofi had submitted published data of Phase III trials from other countries.
The committee had recommended: “Although, the vaccine does not qualify the requirements of waiver of clinical trial, considering the fact that Dengue is a health problem of major concern in the country and can be life-threatening in certain cases, the committee recommends for Market Authorization of the vaccine in the age group of 18-45 years only with the condition to conduct Phase IV clinical trial in time bound manner…”