FDA Approves Experimental H5N1 Bird Flu Vaccine with Reactive AS03 Adjuvant for U.S. Stockpile
Posted: 12/9/2013 4:03:21 PM | with 5 comments
For some time now, vaccine researchers around the world have been on the prowl to create the perfect swine and bird flu vaccines that are both effective and safe, but have come up far short of perfection. In the process, they have added squalene-type “oil-in-water” adjuvants to some influenza vaccines, only to find that it can be risky business.
Squalene Adjuvants Never Licensed Before in U.S.
Squalene adjuvants, which ramp up the immune response, have never been licensed for use in the U.S. However, the Food and Drug Administration (FDA) paved the way for a squalene adjuvant to be included in U.S. vaccines with its November 2013 approval of the first influenza A (H5N1) monovalent “bird flu” vaccine: GlaxoSmithKline’s Q-Pan vaccine that contains the controversial oil-in-water emulsion adjuvant AS03.
Q-Pan vaccine will be added to the U.S. pandemic emergency vaccine stockpile. Although there is no H5N1 influenza pandemic underway to justify fast-tracked approval of the experimental AS03-adjuvanted bird flu vaccine, the speedy FDA approval comes amid mounting evidence that AS03 adjuvants are associated with development of serious autoimmune and neurological disorders like narcolepsy.
GSK’s Squalene-Adjuvanted H5N1 Bird Flu Vaccine: Federally Funded
Approved for adults aged 18 years or older, right now GSK’s Q-Pan H5N1 influenza vaccine is only included in the U.S. vaccine stockpile and is not commercially available for widespread public use … yet.
The U.S. Department of Health and Human Services (DHHS) purchased the vaccine from GSK to stockpile it for a potential future H5N1 pandemic emergency, in the event the bird flu virus develops the ability to spread easily from human to human. GSK will make the vaccine commercially available if directed by the Biomedical Advanced Development and Research Authority (BARDA), which financially supported the vaccine development program through a federally funded contract. 1
[In March 2013, GSK and Texas A&M announced that DHHS had approved the establishment of a $91 million influenza vaccine manufacturing plant facility in Texas that would eventually enable GSK to manufacture influenza vaccine based on the Vivalis novel EB66 duck embryonic stem cell line 2
The FDA cited one study as the basis for their approval of Q-Pan, but reported very few details. The study compared 3,400 adults who were given the vaccine to 1,100 adults who were given a placebo. Out of 2,000 evaluated study subjects, 91 percent of vaccinated adults aged 18 to 64 years “developed a level of antibodies expected to reduce the risk for influenza.” Additionally, 74 percent of vaccinated adults aged 65 years or older also developed this level of immune response.
Vaccine side effects included injection site pain as the most common, but also muscle aches, headache and fatigue. The FDA said it would collaborate with GSK to conduct additional safety and effectiveness studies, “in the event the vaccine is released for public use during an H5N1 influenza virus pandemic.” 3
Controversial H5N1 Lethal Virus Research Hit Roadblocks
There are a couple of things wrong with this picture. First and foremost, research surrounding H5N1 “bird flu” viruses has been rooted in controversy. Remember the two scientists, who were asked to temporarily halt their research projects on the H5N1 strain of the bird flu virus because they were deliberately creating a genetically engineered and more lethal version of the virus in airborne transmissible form that could infect humans? 4
After a firestorm of contentious debate with some scientists calling for an end to the research because it was too risky (the research was later resumed), in March 2013 the FDA delayed its decision regarding approval of GSK’s Q-Pan H5N1 vaccine.
The decision to delay approval came despite a unanimous vote in November 2012 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) to recommend Q-Pan H5N1 vaccine be licensed for inclusion in the national stockpile. Even though a delayed FDA staff decision usually indicates that additional review time is needed for the product, GSK claimed the delay was simply because of an administrative matter. 5
Squalene in Anthrax Vaccines Linked to Gulf War Syndrome
The FDA is well aware that squalene-type vaccine adjuvants like AS03 are controversial and have been linked to a series of anthrax vaccinations given to healthy American soldiers during the Gulf War that were followed by brain and immune system problems in some soldiers. Risks associated with experimental squalene-adjuvanted anthrax vaccines surfaced in the late 1990s when U.S. soldiers in the Gulf War developed brain and immune disorders and tested positive for squalene antibodies. 6 7
The FDA declined to license squalene adjuvants for use in 2009 pandemic H1N1 vaccines released for public use in the U.S. 8 9 10
GSK Pandemic ”Swine Flu” Vaccine & Narcolepsy
However, squalene adjuvants were included in pandemic H1N1 “swine flu” vaccines released in Europe during 2009-2010. In the past few years, a series of studies have produced evidence for an association between GSK’s Pandemrix, which contains AS03, and development of a serious autoimmune and neurological sleep disorder, narcolepsy.
Pandemrix was administered to 30.8 million people in 47 European countries. A total of 795 vaccine adverse event reports have linked Pandemrix with the development of narcolepsy, especially among children. 11
Finnish researchers conducted an epidemiological study to assess the narcolepsy risk among 915,854 people. Approximately 70 percent had been vaccinated. They concluded that there was more than a 12-fold increased risk of developing narcolepsy after vaccination.
In Sweden, researchers compared the incidence of narcolepsy among vaccinated and unvaccinated individuals and found a 6.6-fold increased risk of narcolepsy after vaccination. 12
Even though European health officials said evidence was insufficient to prove a causal relationship between Pandemrix and narcolepsy, the European Union changed its recommendation for the vaccine’s use in individuals younger than 20 years. The European Medicines Agency also said it expects GSK “to take into account the hypothesis generated by the Finnish research in their experimental research programme into the root cause for the association between Pandemrix and narcolepsy.” 13
More Research Connects AS03 Adjuvanted Flu Vaccines to Narcolepsy
Since the preliminary reports out of Finland and Sweden, more studies have drawn similar conclusions. In one 2013 retrospective analysis, UK researchers evaluated narcolepsy cases among 245 children aged 4 to 18 years in England. The study authors noted that there was low overall pandemic H1N1 swine flu vaccine coverage in England.
In total, 75 study patients developed narcolepsy after Jan. 1, 2008 and 11 of those patients had received AS03 adjuvanted Pandemrix vaccine before the onset of the debilitating disorder. In fact, for seven patients, narcolepsy presented within six months.
Based on these results, the researchers estimated at least a 14-fold increase in risk of narcolepsy among children who received GSK’s Pandemrix compared with age-matched children in England who didn’t receive the vaccine. Though Finland estimated that 1 in 16,000 doses could lead to narcolepsy, the English study estimated that 1 in 57,500 and 52,000 doses could lead to the disorder. 14
A second 2013 study assessed the narcolepsy diagnosis rates from 2000 to 2010 in six European countries, identifying 2,608 cases of narcolepsy. Finland and Sweden were the only two countries that recommended Pandemrix for the entire population. The researchers found an increase in narcolepsy diagnoses among children aged 5 to 19 years after the pandemic vaccine campaigns began in Finland and Sweden. There was also an increase in narcolepsy cases in Denmark, although the country had relatively low vaccine coverage. 15
Finland’s National Institute for Health and Welfare analyzed hospital and primary care data and reported that 23 of the 25 adults who developed narcolepsy in Finland during 2009 to 2011 were aged younger than 40 years. None of the patients were aged older than 64 years. Researchers concluded that Pandemrix-vaccinated adults aged from 20 years to 64 years had three to five times the risk of developing narcolepsy as compared with unvaccinated age-matched individuals. 16
Narcolepsy: A Life-Altering Disorder
Narcolepsy, which is sometimes referred to as “sleeping sickness,” is characterized as either an autoimmune or neurological disorder marked by excessive daytime sleepiness, sudden loss of muscle tone and collapse, vivid hallucinations, brief periods of total paralysis and other disabling symptoms. Researchers say genetic factors alone are not sufficient to cause the disease but genes on the HLA antigen immune complex are thought to predispose some individuals to develop narcolepsy. 17 18
Many previously healthy children who have developed Pandemrix-related narcolepsy are unable to go to school or participate in daily activities because they are unable to stay awake or concentrate long enough to participate in normal daily activities. 19
AS03 Pinpointed as Dangerous Vaccine Adjuvant
Vaccine risks often come down to vaccine ingredients and individual biological susceptibilities that place some people at increased risk for vaccine-induced injury and death. The AS03 adjuvanted pandemic H1N1 vaccine is no exception.
AS03, GSK’s proprietary squalene adjuvant, contains a combination of three “oil in water” ingredients, including oil derived from shark livers. Its role in the vaccine is to stimulate a super-charged immune response, in addition to the immune response stimulated by lab-altered, inactivated influenza virus in the vaccine. Yet, there has been little scientific investigation into the individual genetic and biological susceptibilities that could increase risks for some people given squalene-adjuvanted vaccines. 20
MF-59: Another Squalene Adjuvant
MF59 is another squalene adjuvant,21
which has been used for years by another vaccine manufacturer, Novartis, in vaccines used in Europe and other countries. The FDA has not approved vaccines using MF59 for use in the United States, even though drug companies have been lobbying for years to get the FDA to approve MF59 adjuvanted vaccines. 22
The issue with squalene adjuvants could lie in the method of entry. While squalene is an organic compound found in plants, animals and humans,23
and has antioxidant properties when consumed, injecting squalene directly into the body appears to cause the body to react differently. 24
In one 2000 study, injecting squalene into rats led to chronic arthritis, prompting the idea that these molecules could have “wide pathogenetic implications in humans” and may play a role in chronic inflammatory diseases. 25
NVIC Historically Wary of Untested Squalene Adjuvants
NVIC has been cautious of oil-based adjuvants since reports in the 1990s that some experimental anthrax vaccines given to U.S. soldiers in the Gulf War Gulf War included squalene adjuvants that left the soldiers with severe brain and immune system dysfunction. Understanding that vaccine risks can be greater for some individuals than others, NVIC continues to be concerned that squalene adjuvants may increase the risk for vaccine-induced chronic inflammation and autoimmunity in some children and adults, who are genetically predisposed to atypical inflammatory responses and autoimmunity.
NVIC has argued that squalene adjuvants have not been tested compared to placebos in large trials published in scientific journals. In addition, there are no studies specifically evaluating cellular, molecular and DNA changes in the body after squalene-adjuvanted vaccines have been administered to children and adults.
Under Emergency Use Authorization approved by Congress, the FDA has the legal authority to approve and release experimental vaccines for public use whenever federal health officials declare a national “public health emergency.” In 2009, NVIC expressed concern that normal FDA licensing procedures would be by-passed to include squalene adjuvants in pandemic influenza vaccines without adequate testing, which it seems now has been done four years later. 26 27
H5N1 Bird Flu Pandemic Threat Low
FDA’s approval of GSK’s Q-Pan H5N1 squalene-adjuvanted vaccine raises eyebrows because H5N1 bird flu virus infections and related deaths in humans have been confined to those working in the bird farming industry in Asia and the Middle East, who have direct contact with infected birds. Thus far, the H5N1 bird virus does not efficiently transmit among humans.
There is no looming H5N1 pandemic threat in the United States!
Cases of H5N1 reported from 2010 through October 2013 to the World Health Organization have been identified mostly in Indonesia, Egypt, Vietnam, China and Cambodia. 28
Even the FDA admitted the low likelihood of a pandemic H5N1 outbreak in the U.S. in their statement announcing approval of the H5N1 vaccine for national stockpiles: “Most avian influenza A viruses do not infect people,” they stated. However, “H5N1 is an influenza virus with pandemic potential because it continues to infect wild birds with occasional outbreaks of influenza disease in poultry populations, and most humans have no immunity to it.” 29
Squalene adjuvants have never been licensed in the U.S. and legitimate questions are being raised about why there has been a rush to approve an experimental AS03-adjuvanted H5N1 bird flu vaccine for national stockpiling without requiring GSK to produce data demonstrating that the controversial AS03 squalene adjuvant included in the vaccine is safe for everyone. This move by FDA in the absence of a true public health emergency suggests that drug companies put pressure on the regulatory agency to pave the way for future no-hassle “grandfathered” licensing of experimental vaccines containing untested squalene adjuvants.
Only time will tell but, so far, it looks like the scoreboard is Pharma - 1, Public Health Safety - 0.
Asa PB, Wilson RB, Garry GF.
Posted: 12/9/2013 4:03:21 PM | with 5 comments