Friday, December 01, 2017

Philippines Halts Dengue Vaccine After Sanofi Issues Warning


Although the Philippines DOH website appears to be offline this morning (or perhaps simply overloaded by hits), local media reports indicate they have temporarily halted the administration of Sanofi's Dengvaxia® Dengue vaccine to school children following a safety warning from the manufacturer on Wednesday.

Typical of today's reporting comes from CNN.
Gov't halts dengue vaccination program due to health risk 
Metro Manila (CNN Philippines, December 1) — The Department of Health (DOH) temporarily halted its dengue vaccination program after a new study that shows the vaccine poses a risk for those not previously infected by the mosquito-borne virus.

Those at risk are some 70,000 children who were vaccinated under a Health Department program since 2016.

"In the light of this new analysis, the DOH will place the dengue vaccination program on hold while review and consultation are ongoing with experts and key stakeholders and the WHO (World Health Organization) Health Secretary Francisco Duque III said in a media briefing on Friday. 

Duque said 733,713 children from Central Luzon, the region of Cavite, Laguna, Batangas, Rizal, and Quezon, and Metro Manila were administered Dengvaxia. Eight to 10 percent or about 70,000 children have not had dengue yet, the DOH added.

Pharmaceutical company Sanofi on Wednesday said new clinical data analysis showed those not previously infected with dengue and got vaccinated with Dengvaxia could contract "severe disease".
        (Continue . . . .)

If all of this sounds vaguely familiar, it is because a similar concern was raised by researchers years ago, as I noted back in 2010 in Malaysia: Dengue Vaccine Trials
One of the major obstacles in developing a vaccine is that there are four strains of dengue; DEN1 – DEN4. Single strain live attenuated Dengue vaccines have been developed and tested, and seem effective.

They aren’t considered a good solution, however, because having antibodies to one strain of dengue can make an individual more likely to develop the more dangerous hemorrhagic form of dengue when exposed to a different strain.
This phenomenon is known as ADE (Antibody Dependent Enhancement). When infected by a second dengue serotype, the host’s immune system - which already has neutralizing antibodies against the first DENV serotype - misidentifies the second DENV infection as the first strain.
Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.
Although details are scant for now, it appears that something similar to this may be happening when a Dengue naive individual is vaccinated with Dengvaxia®, and then is subsequently infected with dengue.

This Sanofi statement follows:
Sanofi updates information on dengue vaccine
  • New analysis of long-term Dengvaxia® data found differences in vaccine performance based on prior dengue infection
  • Company will ask regulators to update product label to reflect new information
PARIS, FRANCE – November 29, 2017 – Sanofi will ask health authorities to update information provided to physicians and patients on its dengue vaccine Dengvaxia® in countries where it is approved. The request is based on a new analysis of long-term clinical trial data, which found differences in vaccine performance based on prior dengue infection.

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.

“These findings highlight the complex nature of dengue infection. We are working with health authorities to ensure that prescribers, vaccinators and patients are fully informed of the new findings, with the goal of enhancing the impact of Dengvaxia in dengue-endemic countries,” said Dr. Su-Peing Ng, Global Medical Head, Sanofi Pasteur.

About half of the world’s population lives in countries where four serotypes of dengue virus are in circulation. Every year an estimated 390 million dengue infections are reported. People can be infected with dengue up to four times in their lifetime and they can get severely ill after any of these infections.
Surveillance data from some endemic countries indicate that between 70 and 90 percent of people will have been exposed to dengue at least once by the time they reach adolescence. There are many factors that can lead to severe dengue infection. However, the highest risk of getting more severe disease has been observed in people infected for the second time by a different dengue virus.

Dengvaxia is currently indicated in most of the countries for individuals 9 years of age and older living in a dengue-endemic area. In this indicated population, Dengvaxia has been shown to prevent 93 percent of severe disease and 80 percent of hospitalizations due to dengue over the 25 month phase of the large-scale clinical studies conducted in 10 countries in Latin America and Asia where dengue is widespread.

Proposed Label Update

Based on the new analysis, Sanofi will propose that national regulatory agencies update the prescribing information, known as the label in many countries, requesting that healthcare professionals assess the likelihood of prior dengue infection in an individual before vaccinating. Vaccination should only be recommended when the potential benefits outweigh the potential risks (in countries with high burden of dengue disease). For individuals who have not been previously infected by dengue virus, vaccination should not be recommended.

The Sanofi label proposal will be reviewed by national regulatory agencies in each of the countries where the vaccine is registered or under registration. Following their review, each agency might amend the company proposed label.

Financial Information

Taking this information into account and expected future sales, Sanofi will record a charge reflecting depreciation of inventories as well as accelerated depreciation of some tangible and intangible assets in its fourth quarter results.
The impact on the Business Net Income (BNI) is still under assessment but it is expected to be in the range of €100 million after tax. Despite this impact, Sanofi confirms the guidance provided on November 2nd of broadly stable Business EPS(1) at CER in 2017 versus 2016, barring unforeseen major adverse events.

(Continue . . . )

This is a serious setback and a developing story, and I'm sure we're going to hear a lot of fall out from it over the coming months.

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