On December 9, Mexico’s COFEPRIS, the regulatory authority under that country’s Ministry of Health, gave its approval to the world’s first dengue vaccine. Dengvaxia, the vaccine manufactured by the French company Sanofi Pasteur, has cleared phase three trials in Asia and Latin America, where the dengue virus is endemic. COFEPRIS, which translates into English as the “Federal Commission for Protection Against Sanitary Risk”, is to Mexico as the Drug Controller General of India (DCGI) or the FDA are to India and the United States respectively. All new drugs, vaccines and health products must be licensed by COFEPRIS before going on sale in Mexico.
Who can be vaccinated against dengue in Mexico now?
The approval is only for individuals aged 9-45 years, and the vaccine doesn’t, therefore, cover two large sections commonly afflicted by the virus: children and the elderly, who are likely to suffer from existing conditions that make them prone to complications. The vaccine has also been approved only for endemic populations — people living in countries where the virus is known to be in circulation. Tourists to these countries cannot, so far, take the vaccine.
Is the vaccine effective against all strains of dengue?
It is a tetravalent vaccine, which means it offers protection against all four virus serotypes. While the dengue virus circulates in only these four serotypes (Types 1-4), the prevalence of each type varies from outbreak to outbreak. A different strain has been dominant in each of the four outbreaks in India since 1996, for example. This year, as Delhi reported its worst dengue outbreak, Types 2 and 4 were identified as the prevalent strains. According to a COFEPRIS statement, the vaccine “could potentially prevent more than 8,000 hospitalisations and 104 deaths annually and generate savings to public finances by 1,100 million pesos (about Rs 430 crore) a year by the reduction in costs associated with medical care”.
What were the results of the trials of the Dengvaxia vaccine?
The most recent study on the efficacy of the vaccine taken in three doses was published in March this year in the New England Journal of Medicine, on three phase three trials on 35,000 children between 2 and 16 years of age, in Asia Pacific and Latin American countries. The study found that the risk of hospitalisation with dengue fell in patients aged 9 and above, compared to the control group. The study noted that “this reduction in risk was not observed among children under the age of 9” during a four-year follow-up period, but identified a lower risk of hospitalisation for dengue for up to two years among children aged 9-16. The vaccine’s efficacy is not uniform — it is the least in type 2, which is a common strain in India and elsewhere. Based on the advice of its technical advisory group on the phase three trials, the WHO noted in 2014 that the vaccine’s efficacy against all dengue serotypes combined was estimated at 60.8%. The WHO noted 50.3% efficacy for Type 1, and 42.3%, 74.0% and 77.7% for Types 2, 3 and 4 respectively.
Trials also showed the vaccine is more effective in people who have been diagnosed with dengue previously, and not so much in unexposed populations. The NEJM study said this could be a reason the vaccine wasn’t effective in very young children. The WHO report noted that efficacy was 83.7% in seropositive participants (those who had been infected by the virus earlier and hence had some antibodies) and 43.2% in seronegative participants. This is possibly why Mexico, which participated in all stages of trials, approved the vaccine only for endemic populations.
Did India participate in the trials? Has Sanofi applied for clearance in India?
The first trials on Indian adults aged 18-45 in five cities (Delhi, Ludhiana, Bangalore, Pune and Kolkata) found the vaccine to be safe and immunogenic, with results comparable to other clinical trials in Asia. Dr Sharad Agarkhedhar, principal investigator in phase two trials in the five cities, said, “The India results show that the dengue vaccine after three doses was well tolerated and produced antibodies against all four dengue serotypes.”
Using the trial results and its existing database, Sanofi will now attempt a licence application in India. The vaccine cannot be rolled out in India without approval from regulators such as DCGI.
Is a vaccine for dengue being developed in India?
An indigenous dengue vaccine has been under deveopment since 2007, and has completed trials on mice with positive results. It will be tried on primates in the next phase, and is estimated to take another five years to reach the stage of human trials. Research is being carried out by a team led by Dr Navin Khanna at the International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi. The research, funded initially by the Department of Biotechnology, Indo-US Vaccine Action Program and Welcome Trust, received $ 2 million from Infosys Foundation earlier this year. Shortage of funds has slowed down trials, sources said.
How much will the Sanofi vaccine cost?
Statements released by Sanofi and COFEPRIS on Wednesday did not mention the price, but said the company will roll out the vaccine in endemic countries in Asia and Latin America first, where dengue is a significant public health challenge. It will be available in Mexico from next year. The cost of the vaccine is especially important if India is to consider any mass immunisation programme against the disease.
Is it recommended to get vaccination against dengue?
The WHO and governments of all endemic countries, including India, have said periodically that a vaccine would amplify dengue control efforts, especially since no treatment for the disease is available, and management is only based on symptoms. “A safe, effective and affordable dengue vaccine… could be an important tool for reaching the WHO goal of reducing dengue morbidity by at least 25% and mortality by at least 50% by 2020,” the WHO has said.
In its report, the international health body, however, raised questions on whether three doses (six months apart) of the Sanofi vaccine were required. Some experts have pointed out that since the vaccine uses live attenuated forms of all four serotypes, the body will create antibodies against all four strains, even though only one or two may be prevalent at a time. Creating “unnecessary” antibodies may have its repercussions, the experts have said.
With Tabassum Barnagarwala