FDA Approves Adjuvanted H5N1 Vaccine For National Stockpile

Since the H5N1 virus was first identified in 1996 it has expanded into more than 20 different clades and subclades, and new clades and variants continue to evolve. Credit - WHO

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With the recent emergence of H7N9 and MERS-CoV,  some may think of avian H5N1 influenza as `yesterday’s threat’,  but that virus continues to circulate – and mutate into new clades – in many places around the world.  Earlier this month in The Expanding Variants Of H5N1 we looked at an EID report on the emergence of three new variations of the H5N1 virus in Vietnam between 2009 and 2012.

 

And while the number of human H5N1 infections being reported in Indonesia, China, and Egypt have been much reduced over the past couple of years, Cambodia has seen more cases this year than their total over the 8 years before 2013 (see Nov 14th report Cambodian MOH Announces Two New H5N1 Cases.

 

Although some early experimental H5N1 vaccines were produced and stockpiled by the United States government in 2006 and 2007, the clades those shots were based on are no longer dominant.  Additionally, early human testing revealed a very poor immune response when using the standard antigen load of 15 ug.  In fact, it was discovered that it might take a whopping 12x’s the antigen (2 - 90 ug shots, 21 days apart) to produce a reasonable level of protection.

 

With a limited ability to produce H5N1 antigen in bulk, a requirement for 2-90 ug shots would dramatically reduce the number of vaccines that could be delivered in the first 6 to 12 months of a pandemic.

 

The solution offered was the inclusion of an adjuvant -  proprietary chemicals that are added to vaccines to increase the recipient’s immune response, and that can dramatically lower the amount of antigen needed in a vaccine. Since they are viewed by some as somewhat controversial, adjuvants were not used in flu vaccines in the United States during the 2009 H1N1 pandemic, but they were widely used in Canada and Europe.

 

While millions received adjuvanted vaccines during the 2009 pandemic without incident, a small number of children in Europe developed a rare neurological illness (narcolepsy) in the months after receiving the adjuvanted Pandemrix vaccine.

 

Although the adjuvant is being looked at, the actual cause of this illness has not been established.  The exact mechanism behind this Pandemrix-Narcolepsy link remains a medical mystery. Our understanding of this neurological disorder is very limited, as well.

 

In February of this year the UK’s HPA published a statement ( see Pandemrix Vaccine Linked To Childhood Narcolepsy In England) that found the absolute risk of a child developing narcolepsy from the adjuvanted Pandemrix flu shot appeared to be about 1 in 55,000. 

Over the past several years GSK has been moving through the approval process on their candidate monovalent, adjuvanted pandemic H5N1 influenza vaccine. Data published in November of 2012 indicated that they’d found a good immune response with their adjuvanted vaccine with just two doses of 3.75 ug, given 21 days apart. 

 

The adjuvant is provided in a separate vial, and is pre-mixed prior to injection.  You can view a Power Point Presentation on the FDA Website with the details of those trials at this link.

 

All of which brings us to a late Friday afternoon announcement from the FDA, that they have approved the first adjuvanted flu vaccine for the prevention of H5N1 influenza . This approval is for inclusion in the National Strategic Stockpile, not for commercial use, and is approved only for those over the age of 18.

 

 

FDA NEWS RELEASE

For Immediate Release: Nov. 22, 2013

Media Inquiries: Jennifer Rodriguez, 301-796-8232, jennifer.rodriguez@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA,OCOD@fda.hhs.gov

FDA approves first adjuvanted vaccine for prevention of H5N1 avian influenza

Vaccine to supplement National Stockpile, not intended for commercial availability

The U.S. Food and Drug Administration today approved the first adjuvanted vaccine for the prevention of H5N1 influenza, commonly known as avian or bird flu. The vaccine, Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, is for use in people 18 years of age and older who are at increased risk of exposure to the H5N1 influenza virus.

Avian influenza is an infectious disease of birds caused by certain influenza A viruses. Most avian influenza A viruses do not infect people. However some viruses, such as H5N1, have caused serious illness and death in people outside of the U.S., mostly among people who have been in close contact with infected and ill poultry. When people do become infected with H5N1, about 60 percent die, according to the World Health Organization. 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.

 

“This vaccine could be used in the event that the H5N1 avian influenza virus develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the globe,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research. “Vaccines are critical to protecting public health by helping to counter the transmission of influenza disease during a pandemic.”

 

The H5N1 avian influenza vaccine is not intended for commercial availability. The U.S. Department of Health and Human Services has purchased the vaccine from the manufacturer, ID Biomedical Corporation of Quebec, Quebec City, Canada (a subsidiary of GlaxoSmithKline Biologicals), for inclusion within the National Stockpile for distribution by public health officials if needed.

 

The vaccine is made using an egg-based manufacturing process, which is also used for ID Biomedical Corporation’s seasonal influenza vaccine, FluLaval. It contains the adjuvant AS03, an oil-in-water emulsion. An adjuvant is a substance incorporated into some vaccines to enhance or direct the immune response of the vaccinated individual. The adjuvant makes it possible to use a small amount of influenza protein per dose of vaccine to elicit the desired immune response in an individual to prevent influenza disease. Reducing the amount of influenza protein per dose helps to increase the total number of doses of a safe and effective vaccine available for the public during a pandemic.

 

The H5N1 component and the AS03 adjuvant component are supplied in two separate vials, which must be combined prior to use. The vaccine is administered via intramuscular injection in two doses, 21 days apart.

 

The evaluation of safety compared approximately 3,400 adults 18 years of age and older who received the vaccine to about 1,100 adults who received placebo in a multi-center study. The most common side effect reported during the clinical studies among the vaccine recipients was injection site pain. Muscle aches, headache, fatigue and injection site redness and swelling were also common. To determine how well the vaccine works, the immune response was evaluated in about 2,000 of the vaccinated adults. The results showed that 91 percent of individuals between the ages of 18 and 64 years and 74 percent of individuals 65 years and older who received the two-dose regimen developed antibodies at a level that is expected to reduce the risk of getting influenza.

 

The manufacturer will collaborate with the FDA and other U.S. governmental agencies on plans to collect additional safety and effectiveness data through U.S. government-sponsored studies of the vaccine, in the event that it is used during an H5N1 influenza virus pandemic.

HPA: Pandemrix Vaccine Linked To Childhood Narcolepsy In England

 

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Pandemrix was the adjuvanted pandemic H1N1 flu shot developed by GlaxoSmithKline (GSK) and distributed to more than 30 countries beginning in the fall of 2009. This vaccine included a squalene-based component called AS03, used as a adjuvant.

 

Adjuvants are additives that are used to increase the immune response to a vaccine. Their use can allow the `stretching’ of the vaccine supply, as shots can contain a smaller amount of antigens.

 

While they have been used in Europe and in Canada, adjuvanted flu vaccines have not been licensed for use in the United States.

 

Roughly a year after the vaccine was deployed, we began to see reports of an unusual rise in the number of children in Finland (a country where Pandemrix was used) diagnosed with a rare neurological disorder called narcolepsy.

 

For early coverage of this story, you may wish to revisit Finland Suspends Use of Pandemrix Vaccine and EMA To Review Pandemrix Vaccine, both of which I wrote in August of 2010.

 

Despite some conflicting and incomplete data the European Medicines Agency issued a statement in July of 2011 recommending:

 

In persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people.

 

Finland also convened a Narcolepsy Task Force (see Finland: Task Force Report On Pandemrix-Narcolepsy Link) that confirmed an association – as yet unexplained – between receipt of the vaccine and an increase in narcolepsy in children between the ages of 4 and 19.

 

In September of 2012, the ECDC released a 164 page technical report called Narcolepsy In Association With Pandemic Influenza Vaccination in which the summary found:

 

The case–control study confirms an association between vaccination with Pandemrix® and an increased risk of narcolepsy in children and adolescents (5 to 19 years of age) in Sweden and Finland that originally reported on this issue (signalling countries). No such association was found in adults in these two countries.

 

 

Fast forward to yesterday, and we have a press release from the HPA on a study – just published in the BMJ - that has also found a link between the Pandemrix vaccine and childhood narcolepsy in the UK. 

 

First a link to the study, then some excerpts from the HPA release.

 

 

Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f794 (Published 26 February 2013)

Cite this as: BMJ 2013;346:f794

 

Conclusion The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.

(Continue . . . )

 

While unproven, the authors raise the possibility that the adjuvanted vaccine – rather than directly causing narcolepsy – might have accelerated the process in children who would eventually have gone on to develop the disorder. 

 

A significant dip in the `background rate’ of narcolepsy over the next few years in countries that saw a spike after 2009 ASO3 vaccination would help give this theory more weight.

 

A paucity of safety trials on children, and the public’s memories of the 1976 Swine Flu vaccine debacle, led the HHS to decide not to allow adjuvants in the pandemic flu vaccines deployed in the United States, despite urging by the global community.

 

The HPA has put together the following summary.

 

Pandemic flu vaccination linked to narcolepsy in UK children

27 February 2013

Health Protection Agency (HPA) scientists have found evidence of an association between Pandemrix flu vaccination and narcolepsy in children in England, according to the findings of a study published in the British Medical Journal. These findings are consistent with previous studies from Finland and Sweden which identified a similar association.

 

In collaboration with researchers from Papworth and Addenbrooke’s hospitals in Cambridge, the study looked at 75 children aged between four and 18 who were diagnosed with narcolepsy from January 2008 and who attended sleep centres across England. Eleven of these children had been vaccinated with Pandemrix before their symptoms began, seven of these within six months. This suggests a risk of narcolepsy following vaccination with Pandemrix of around one in every 55,000 doses of the vaccine.

 

The Pandemrix vaccine was recommended for use in children at risk of serious complications from influenza during the pandemic flu outbreak in 2009/10. It was also used occasionally in children during the 2010/11 flu season. Since July 2011 the use of Pandemrix in people under the age of 20 across Europe has been restricted.

 

Although prior to this study, there was no evidence to suggest an association in the UK, on the basis of the findings from Finland the HPA launched an in depth study in February 2011 with narcolepsy experts across England. This investigated whether there was evidence of an association between narcolepsy and Pandemrix as used in the UK.

 

Lead author Professor Liz Miller, a consultant epidemiologist with the HPA, said: "These findings suggest there is an increased risk in children of narcolepsy after Pandemrix vaccination and this is consistent with findings from studies in other European countries. However, this risk may be overestimated by more rapid referral of vaccinated cases. Long term follow up of people exposed to Pandemrix is needed before we can fully establish the extent of the association.

 

“Our findings have implications for the future licensing and use of adjuvanted pandemic vaccines. Further studies to assess the possible risk associated with other vaccines used in the pandemic, including those with and without adjuvants, are also needed to inform the use of such vaccines in the event of a future pandemic.”

 

Study co-author Dr John Shneerson, consultant physician from the Respiratory Support and Sleep Centre at Papworth Hospital in Cambridge, said: “Narcolepsy is thought to be due to a loss of function of a small group of cells in one of the sleep centres in the brain, as a result of an abnormal reaction of the body’s immune system. Pandemrix may have triggered an immune reaction against the sleep centre cells in those children who were genetically predisposed to develop narcolepsy. This study has been important in helping to shed light on the mechanism of how narcolepsy can develop.”

 

Narcolepsy is a chronic neurological disorder caused by the brain's inability to control sleep, particularly REM (dream) sleep. It leads to excessive daytime sleepiness usually accompanied by sudden episodes of muscle weakness triggered by strong emotions such as laughter – this is known as cataplexy. Narcolepsy has a genetic component but this has to be triggered by other factors in order for the condition to appear. 20,000 people in the UK are through to have narcolepsy - drug treatment and lifestyle measures are usually effective in relieving the symptoms.

Ends

 

The exact mechanism behind this Pandemrix-Narcolepsy link remains a medical mystery. Our understanding of this neurological disorder is very limited, as well.  

 

The absolute risk of a child developing narcolepsy from the Pandemrix flu shot appears appears to be about 1 in 55,000. The authors warn that:

 

`Our findings have implications for the future licensing and use of adjuvanted pandemic vaccines’.

 

While a handful of countries had reported increases in post-vaccination narcolepsy, the link between the AS03 adjuvanted vaccine and childhood narcolepsy in the UK has not, until now, been quantified.

 

This study found the increased risk was similar to that previously reported from Finland.

GSK Pledges To Release All Drug Trial Data

 

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It’s genuinely big news this afternoon that GSK (Glaxo-Smith-Kline) has pledged that they will publish all results of clinical study reports (CSRs) and clinical trials, not only going forward, but also going back on all approved medications developed since the year 2000.

 

It is estimated that roughly half of all clinical trials never see the light of day, and in 2010 an NHS Health Technology Assessment concluded that:

 

Studies with significant or positive results were more likely to be published than those with non-significant or negative results . . .

 

I’ve written in the past on the reluctance of Roche to release all of their clinical trial data on Tamiflu, and in RCTs: All That’s Gold Standard Doesn’t Glitter, we looked at a Johns Hopkins Study on pediatric clinical trials that found:

 

Overall, 41 percent of the 146 trials in the review had improper or poorly described randomization techniques. Industry-funded trials were six times more likely to have high risk for biased randomization than government-funded trials or those funded by nonprofit organizations.

 

While public concerns over industry reporting bias and secrecy have grown over the years, the charge has really been led by All Trials Registered, All Results Reported.

 

An initiative of Sense About Science, Bad Science, BMJ, James Lind Initiative, the Centre for Evidence-based Medicine and others, their grassroots campaign has put considerable pressure on pharmaceutical companies to release their data.

 

Today, in what can only be described as a major victory for the AllTrials campaign, GSK posted the following announcement on their corporate website, pledging to publish detailed drug trial data.

 

GSK announces support for AllTrials campaign for clinical data transparency

Issued: Tuesday 5 February 2013, London UK

GSK today further demonstrated its commitment to clinical trial transparency by announcing its support for the AllTrials campaign. The campaign is calling for registration of clinical trials and the disclosure of clinical trial results and clinical study reports (CSRs) to help drive further scientific understanding.

 

GSK already publicly discloses a significant amount of information about its clinical trials. The company registers and posts summary information about each trial it begins and shares the results of all its clinical trials – whether positive or negative – on a website accessible to all. Today this website includes almost 5,000 clinical trial result summaries and receives an average of almost 11,000 visitors each month. The company has also previously committed to seek publication of the results of all of its clinical trials that evaluate its medicines to peer-reviewed scientific journals.

 

Expanding on this, GSK is committing to make CSRs publicly available through its clinical trials register. CSRs are formal study reports that provide more details on the design, methods and results of clinical trials and form the basis of submissions to the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory agencies. From now, GSK will publish CSRs for all of its medicines once they have been approved or discontinued from development and the results have been published. This is to allow for the data to be first reviewed by regulators and the scientific community. Patient data in the CSRs and their appendices will be removed to ensure patient confidentiality is maintained.

 

In addition, while there are practical challenges, the company also intends to publish CSRs for clinical outcomes trials for all approved medicines dating back to the formation of GSK. This will require retrieval and examination of each historic CSR to remove confidential patient information. Given the significant volume of studies involved, the company will put in place a dedicated team to conduct this work which it expects to complete over a number of years. Posting will take place in a step-wise manner, with priority given to CSRs for its most commonly prescribed medicines.

(Continue . . . )

 

Hopefully this will be the first of many such industry announcements.

Finland: Task Force Report On Pandemrix-Narcolepsy Link

 

 

 

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Just over a year ago reports began to come out of Finland suggesting a link between an increase in the rate of narcolepsy among adolescents and GSK’s adjuvanted Pandemrix vaccine.

 

For early coverage of this story, you may wish to revisit Finland Suspends Use of Pandemrix Vaccine and EMA To Review Pandemrix Vaccine, both of which I wrote in August of 2010.

 

Despite some conflicting and incomplete data the European Medicines Agency issued a statement last July recommending:

 

In persons under 20 years of age Pandemrix to be used only in the absence of seasonal trivalent influenza vaccines, following link to very rare cases of narcolepsy in young people.

 

 

Note: The use of GSK’s 2009 monovalent Pandemrix vaccine has been largely supplanted by the introduction of last year’s trivalent vaccine, so the impact of this ruling should be minimal.

 

Stockpiles were released last winter in the UK during their surge in flu cases (see UK: To Release Pandemrix Vaccine Stockpile). 

 

The EMA maintained, however, that despite these concerns over the Pandemrix vaccine, the overall benefit-risk remains positive.

 

Since then, we’ve seen a study that linked an increase in narcolepsy to the flu virus itself (see Stanford Study Finds Influenza – Narcolepsy Connection) -  further confusing matters.

 

 

Today, Finland’s National Institute For Health and Welfare Narcolepsy Task Force has released a report where they find an association between the Pandemrix vaccine and increased rates of narcolepsy in children between the ages of 4 and 19.

 

 

Association between Pandemrix and narcolepsy confirmed among Finnish children and adolescents

1 Sep 2011

An association between Pandemrix and narcolepsy among children and adolescents in Finland is confirmed

 

In its final report, the National Narcolepsy Task Force confirms the tentative conclusion published in its Interim Report last January that the Pandemrix vaccine used in the winter of 2009–2010 contributed to the increased incidence of narcolepsy observed among 4–19-year-olds in Finland. According to the report, the increased risk associated with vaccination amounted to six cases of narcolepsy per 100 000 persons vaccinated in the 4–19 age group during the eight months following vaccination. This was 12.7 times the risk of a person in the same age group who had not been vaccinated. No increased incidence of narcolepsy was observed among children under the age of four or among adults over the age of 19.

 

In all the cases examined, narcolepsy associated with Pandemrix vaccination has been identified in persons who carry a genetic risk factor for narcolepsy. Because of this very strong association with the genetic risk factor which regulates immune responses, narcolepsy is considered an immune-mediated disease.

 

In approximately one quarter of those who developed narcolepsy following Pandemrix vaccination, the THL Immunology laboratory found antibodies binding to the AS03 adjuvant component of the vaccine. Adjuvants containing squalene have not previously been reported to induce the production of antibodies. The significance of this preliminary observation will be the subject of further research.

(Continue . . . )

 

 

While more research is needed to nail down exactly what happened, and why, a few key points to ponder.

 

• Of the 3 dozen countries that used the Pandemrix vaccine in 2009-2010, only Finland and Sweden have documented an increase in Narcolepsy that they can link to the Pandemrix vaccine.
• At least a dozen countries reported increased rates of narcolepsy during that time period, including some countries where the vaccine was not used.
• In all the cases the task force examined, narcolepsy associated with Pandemrix vaccination was identified in persons who carry a genetic risk factor for narcolepsy
• Regarding the use of the vaccine, despite the the `unforeseen and deeply regrettable cases of narcolepsy’, Finland’s Narcolepsy taskforce found that its use probably saved lives and that `overall benefit-risk balance remains positive.’
• While unsure of its significance, researchers found antibodies binding to the AS03 adjuvant component of the vaccine in roughly 25% of the cases examined.
• And finally, adjuvanted flu vaccines like Pandemrix were not used in the United States. 

 

Despite rare adverse side effects such as narcolepsy, flu vaccines have an excellent safety profile, and remain our best weapon against a virus that kills tens of thousands every year.

 

Taking any medicine – including a flu vaccine – entails a small degree of risk.  But those risks pale when compared to the risks from catching the flu.

 

And with the potential for seeing an increase in antiviral resistant flu viruses that might limit your treatment options in the future (see Australia Reports Cluster Of Antiviral Resistant H1N1), doing what you can now to protect yourself against infection this winter makes a lot of sense.

EMA Recommends Interim Measures For Pandemrix Vaccine

 

 

 

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The supposed link between GSK’s Pandemrix Vaccine and an increase in narcolepsy among children and adolescents in a handful of countries has been covered often in this blog over the past 6 months.

 

Today, new we’ve information from the EMA.  But first, a quick review of the story to date.

 

In late August of 2010, shortly after the declared end of the H1N1 pandemic, reports of a possible increase in narcolepsy among children and adolescents who received GSK’s adjuvanted Pandemrix vaccine began to emerge from Finland.

 

On August 25th, I reported Finland Suspends Use of Pandemrix Vaccine, and two days later I blogged on the European Medicines Agency’s plan to review the evidence (see EMA To Review Pandemrix Vaccine).

 

Since then we’ve seen several interim reports that failed to find conclusive evidence of a link between the Pandemrix vaccine and narcolepsy, but which did find reasons to continue the investigation.

 

Sweden: No Link Between Pandemrix And Narcolepsy

EMA Update On The Pandemrix-Narcolepsy Investigation

 

On February 1st, Finland’s National Institute for Health and Welfare released an interim report on what they called a probable link between GSK’s Pandemrix vaccination, and an increase in narcolepsy in children and adolescents 4-19 years of age.

 

Finland: Statement On Pandemrix And Narcolepsy Link

 

A week later, the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) has issued a statement on the potential link between GSK’s Pandemrix vaccine and an increase in rates of narcolepsy among recipients aged 4 to 19.

 

 

While stating that further investigation is warranted concerning narcolepsy and vaccination against influenza (H1N1) 2009 with Pandemrix and other pandemic H1N1 vaccines the advisory group also states that this does not appear to have been a world-wide phenomenon.

 

WHO: GACVS Statement On Narcolepsy And Vaccination

 

Roughly 10 days later, the European Medicines Agency (EMA) released a statement (see EMA: Added Concern, But Insufficient Evidence To Link Vaccine To Narcolepsy) that stated that that its Committee for Medicinal Products for Human Use (CHMP) has reviewed Finnish data on the suspected link between Pandemrix vaccine and an increase in narcolepsy, and has concluded that the new evidence `added to the concern’, but was as yet insufficient to establish a causal relationship.

 

 

Today (April 15th, 2011), in the latest installment in this ongoing investigation, the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Pandemrix’s product information be amended to include concerns over a suspected link to narcolepsy.

 

 

15/04/2011

European Medicines Agency recommends interim measures for Pandemrix

Updated prescribing advice highlights preliminary results from epidemiological studies on narcolepsy; further research needed

 

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the product information for Pandemrix should be amended to advise prescribers to take into account preliminary results from epidemiological studies on Pandemrix and narcolepsy, and to perform an individual benefit-risk assessment when considering the use of Pandemrix in children and adolescents. This is an interim measure pending the outcome of the European review, expected to conclude in July 2011.

 

The CHMP reviewed all available data, including new findings from Sweden and France on the suspected link between narcolepsy in children and adolescents and Pandemrix. The CHMP concluded that, following the earlier results of an epidemiological study from Finland, the new evidence strengthened the signal in children and adolescents, but that the data had methodological limitations. The relationship between Pandemrix and narcolepsy is still under investigation.

 

Preliminary results of the Swedish registry study from October 2009 to December 2010 on Pandemrix vaccination and the risk of narcolepsy indicates a four-fold increase of cases of narcolepsy in children and adolescents (below 20 years of age) who received Pandemrix compared with unvaccinated people of the same age. The additional risk corresponds to an additional 3-4 narcolepsy cases per 100,000 vaccinated subjects. These results are broadly in line with the study results from Finland indicating an association between Pandemrix and narcolepsy in children and adolescents. The study did not identify any increased risk in adults. The CHMP concluded that the study was well conducted, although it has inherent limitations.

 

An analysis of narcolepsy reports in France provides some further evidence.

 

The lack of a clear increase in reports of narcolepsy following Pandemrix in other EU and non-EU countries may point towards the influence of other unknown factors affecting the trend seen in some countries. Also, there is currently no clearly identified biological plausibility for an association between Pandemrix and narcolepsy, and further non-clinical studies, especially in the juvenile setting, are needed.

 

The CHMP considers it important to gather more data on the use of Pandemrix and related vaccines in a variety of countries to further assess this concern. A variety of research efforts are now ongoing. These include an epidemiological study of narcolepsy and pandemic vaccines conducted by the European Centre for Disease Prevention and Control (ECDC) through a network of research and public health institutions (VAESCO) in nine European Union Member States, and an epidemiological study conducted by Glaxo Smith Kline (the marketing authorisation holder of Pandemrix) in Canada. Preliminary results of the VAESCO study and of the Canadian study are expected by July 2011.

 

The CHMP is working with experts from across the EU to assess the possible safety concern and any impact on the benefit-risk balance of Pandemrix. The CHMP plans to hold an expert meeting with participation of international experts, the World Health Organization (WHO) and ECDC.

 

The European Medicines Agency will provide updates as new information becomes available.

(Continue . . . )

 

 

The increase in narcolepsy among children in just a few of the nations that deployed the Pandemrix vaccine remains a medical mystery.   Investigations continue.

 

While some link between the vaccine and the condition may well exist, researchers are looking for a third factor – an unknown catalyst – that may have affected residents of some countries but not others.

 

The Pandemrix vaccine was not used in the United States.

 

This is an evolving story, and for now there are more questions than answers.

GSK Statement On Pandemrix-Narcolepsy Report

 

 

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GlaxoSmithKiline (GSK), the manufacturers of the Pandemrix vaccine which some researchers believe may be linked to an increase in narcolepsy among children aged 4-19 (see Finland: Statement On Pandemrix And Narcolepsy Link), has released a statement of their own today.

 

With other investigations underway, GSK believes it is premature to draw any conclusions on any link between their vaccine and increases in narcolepsy. 

 

I’ve just excerpted a few paragraphs from this press release.  Follow the link below to read it in its entirety.

 

 

Update on Pandemrix™ and interim Finnish report on narcolepsy

Issued: 1 February 2011

GSK is aware of today’s interim report by the Finnish National narcolepsy committee ^[1] on their investigation into reported cases of narcolepsy in Finland. This investigation is independent of a broader ongoing European Medicines Agency (EMA) investigation initiated in 2010. GSK is reviewing the report and believes it would be premature to draw any conclusions on a potential association between Pandemrix and narcolepsy until this European investigation has been completed.

 

Patient safety is of paramount importance to GSK and we have been working closely with the EMA and other national regulatory organisations to better understand the situation since reports of narcolepsy after vaccination with Pandemrix were first received. The company recognises the value of ongoing independent research to add further information.

 

The EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed all of the available data on the suspected link between narcolepsy and Pandemrix in September 2010 and stated at that time that the benefit risk balance for Pandemrix remained positive.  Since then GSK has continued to provide EMA with information on narcolepsy cases being reported to the company and to date there has been no change in EMA’s position.

 

(Continue . . . )

Sweden: No Link Between Pandemrix And Narcolepsy

 

 

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From CIDRAP News tonight, a report by Lisa Schnirring on the findings of Sweden’s Medical Products Agency’s investigation into a possible link between GSK’s Pandemrix vaccine and narcolepsy.

 

The preliminary investigation has found no apparent link between the vaccine and the neurological disorder, as many of the recent cases never received the vaccine. 

 

Follow the link to read the entire report.

 

Sweden finds no link between H1N1 vaccine, narcolepsy

Lisa Schnirring Staff Writer

Sep 9, 2010 (CIDRAP News) – Preliminary results from an investigation by Swedish regulators into reports of narcolepsy in people who received a 2009 H1N1 vaccine found no link between the immunization and the condition.

In a report yesterday from the country's Medical Products Agency, investigators said they found that narcolepsy developed both in people who had and who had not received the vaccine, Finland-based YLE News reported yesterday.

(Continue . . . )

GSK Press Statement On Pandemrix Investigation

 

 

 

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GSK (Glaxo Smith-Kline), manufacturers of the adjuvanted Pandemrix vaccine that has been linked by media reports to a small number of cases of narcolepsy in children – has released a statement today for journalists and investors.

 

 

Reports of narcolepsy in Europe following vaccination with Pandemrix™

WEBWIRE – Friday, September 03, 2010

London UK - GSK initially became aware of possible cases of narcolepsy following vaccination with the adjuvanted H1N1 pandemic vaccine Pandemrix through adverse event reports received by the Swedish Medical Products Agency, and subsequently via media reports in Finland.

 

Information on the individual cases remains limited at present, but GSK is conducting its own investigation in an effort to gather as much additional data as possible regarding the reported cases, and is working closely with key regulatory authorities, including the European Medicines Agency (EMA).

(Continue . . .)

 

 

Although some media reports – particularly those by anti-vaccination activists – have worded stories to suggest that a `probable link’ between the vaccine and these cases of narcolepsy has been established . . .  right now, there is no proof of causation.

 

With further investigation, a link may be established. Flu vaccines have a good safety record, but on rare occasions serious side effects have been noted.

 

That said, the background rates of narcolepsy are poorly understood, and the condition is generally believed to be under-diagnosed.

 

It will take time to know whether the vaccine was responsible for this upsurge in reported cases. 

 

But other possibilities exist.

 

Greater scrutiny, better reporting systems, and the public’s concern over the vaccine’s safety might well account for a greater number of diagnoses of narcolepsy in children over the past 6 months.

 

Essentially, the harder we look for diseases, the more we are likely to find.

 

We’ll simply have to wait to see where these investigations lead.

 

 

 

EMA To Review Pandemrix Vaccine

 

 

# 4840

 

 

The EMA (European Medicines Agency) is a London based EU regulatory agency that is responsible for the scientific evaluation of drugs developed by pharmaceutical companies for use in the European Union. 

 

It is roughly the EU equivalent to the United State’s FDA.

 

Today the EMA announced that they will review GSK’s Pandemrix vaccine to see if they can ascertain any causal link between it - and reports of unusual occurrences of narcolepsy – mostly in children, reported in Sweden and Finland  (see Finland Suspends Use of Pandemrix Vaccine) in recent days.

 

For now, no causal link has been established and the number of reported cases of narcolepsy (which afflicts several thousand  Europeans each year) remains small. 

 

Still, the number of cases among recently vaccinated children has been sufficient to raise concerns, and an investigation will be conducted.

 

 

The EMA press release (h/t Ironorehopper on FluTrackers) provides additional details.

 

 

European Medicines Agency starts review of Pandemrix

The European Medicines Agency has launched a review of Pandemrix on the request of the European Commission to investigate whether there is a link between cases of narcolepsy and vaccination with Pandemrix. A limited number of cases was reported, all collected through spontaneous reporting systems, mainly in Sweden and Finland. Pandemrix, an influenza vaccine, has been used since September 2009 for vaccination against H1N1 influenza in at least 30.8 million Europeans.

 

Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. Its precise cause is unknown, but it is generally considered to be triggered by a combination of genetic and environmental factors, including infections.

 

Although the cases of narcolepsy have been reported in temporal association with the use of Pandemrix, it is at present not known if the vaccine caused the disorder. The Agency’s Committee for Medicinal Products for Human Use (CHMP) will look carefully at all of the available data to determine whether there is evidence for a causal association. As part of this evaluation the Committee will also consider the so-called background rate for narcolepsy, i.e. the number of cases that would normally be expected to be diagnosed.

 

The Committee will be working with experts from across the EU to assess this possible safety concern and any impact on the benefit risk balance of Pandemrix. The Committee will consider at its September 2010 meeting the need for any provisional measures pending completion of the evaluation.

 

The Agency is also liaising with the European Centre for Disease Prevention and Control (ECDC), international regulatory partners and the World Health Organization (WHO).

 

The European Medicines Agency will provide updates as new information becomes available.

Notes:

1. On 24 August 2010, Finland’s National Institute for Health and Welfare recommended that vaccination with Pandemrix be discontinued until the suspected link with narcolepsy is thoroughly evaluated.
2. Pandemrix has been authorised in the European Union since September 2009. The vaccine was extensively used during the 2009 (H1N1) pandemic, with at least 30.8 million Europeans vaccinated.

 

 

 

The Pandemrix vaccine was an adjuvanted monovalent pandemic H1N1 shot, and as such, was not licensed for use in the United States.