Aflunov

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Aflunov have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Aflunov are continuously monitored. Side effects reported with Aflunov are carefully evaluated and any necessary action taken to protect patients.

Aflunov received a marketing authorisation valid throughout the EU on 29 November 2010.

Aflunov can only be obtained with a prescription and should be used according to official recommendations.

The vaccine is given by injection into the muscle of the thigh or shoulder in two doses, at least 3 weeks apart. In an officially declared pandemic caused by the H5N1 strain of influenza A, people who have already been vaccinated with Aflunov (with one or two doses) may be given only one more dose, instead of the two doses recommended for unvaccinated people.

For more information about using Afllunov, see the package leaflet or contact your doctor or pharmacist.

Aflunov is a vaccine to be given before or during a flu pandemic to protect against a new strain of flu. A flu pandemic happens when a new strain of the flu virus can spread easily from person to person, because people do not have immunity (protection) against it. Health experts are concerned that a future flu pandemic could be caused by the H5N1 strain of the virus, an infection that can spread from birds to humans (a ‘zoonotic’ infection).

Vaccines work by preparing the immune system (the body’s natural defences) to defend itself against a specific disease. This vaccine contains some parts of the H5N1 virus. The virus has first been inactivated so that it does not cause any disease. When a person is given the vaccine, the immune system recognises the virus parts in the vaccine as ‘foreign’ and makes antibodies against them. When the person comes into contact with the virus, these antibodies, together with other components of the immune system, will be able to kill the virus and help protect against the disease.

The vaccine contains an ‘adjuvant’ (a compound containing oil) to increase the vaccine’s effectiveness.

Aflunov has been shown to produce sufficient antibodies to stimulate an immune response and protect against H5N1.

At the time of the initial marketing authorisation, two main studies using a strain called A/Vietnam/1194/2004 (H5N1)-like strain (NIBRG-14) provided data on vaccination with Aflunov in healthy adults aged below and above 60 years. In one study involving 3,372 people, subjects were given either a seasonal flu vaccine followed by two doses of Aflunov 3 weeks apart, or placebo (a dummy vaccine) followed by two doses of a seasonal flu vaccine 3 weeks apart. In this study, 21 days after the second injection, around 90% of people aged below 60 years and around 80% of those aged above 60 years had levels of antibodies that would protect them against H5N1.

In the second study 240 adults were given Aflunov using different vaccination schedules. The studies looked at the ability of the vaccine to trigger the production of antibodies (‘immunogenicity’) against the flu virus. This study established that Aflunov should be given as two doses at least 3 weeks apart.

A third study, using a vaccine with strain A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23), was carried out in 343 adults aged below and above 60 years. The study showed that 21 days after the second injection, around 70% of adults below 60 years and around 64% of adults above 60 years produced an acceptable antibody response.

A study carried out in 420 children aged between 6 months and 8 years of age received two doses of Aflunov given 3 weeks apart. The vaccine was shown to bring about protective levels of antibodies to a satisfactory level.  In an additional study Aflunov was also found to produce protective levels of antibodies in children aged 6 months to 17 years.

For the full list of side effects and restrictions with Aflunov, see the package leaflet.

The most common side effects with Aflunov in adults (which may affect more than 1 person in 10) are headache, myalgia (muscle pain), reactions at the site of injection (swelling, pain, hardening and redness), tiredness, malaise (generally feeling unwell) and chills.

In addition, in children aged 3 to 17 years of age the most common side effects may also include nausea (feeling sick), diarrhoea and vomiting, sweating,  injection site tenderness and bruising.

In children between the age of 6 months and 35 months of age fever, reactions at the site of injection (swelling, bruising, hardening and redness), irritability, tenderness, unusual crying, sleepiness, change in eating habits, diarrhoea, fever, vomiting and sweating are the most common side effects.

Aflunov must not be given to people who have had an anaphylactic reaction (severe allergic reaction) to any of the components of the vaccine, including those found at trace (very low) levels (egg or chicken protein, ovalbumin [a protein in egg white], kanamycin or neomycin [antibiotics], formaldehyde and cetyltrimethylammonium bromide). However, it may be appropriate to give the vaccine to these people during a pandemic, as long as facilities for resuscitation are available.

It was noted that it is likely that a H5N1 strain of influenza will cause a pandemic in the future and Aflunov was shown to produce sufficient antibodies to stimulate an immune response and protect against H5N1. The safety profile was also considered acceptable. tThe European Medicines Agency therefore decided that Aflunov’s benefits are greater than its risks and it can be authorised for use in the EU.

Aflunov is a vaccine. It consists of a suspension for injection that contains some parts (outer membranes) of the influenza (flu) virus strain called A/VietNam/1194/2004.

Aflunov was expected to be used in adults and the elderly to protect against flu caused by the H5N1 strain (type) of the influenza A virus.

Aflunov is a 'prepandemic' vaccine. This is a special type of vaccine that is intended to protect against a strain of flu that may cause a future pandemic. A flu pandemic happens when a new strain of flu virus appears that can spread easily from person to person because people have no immunity (protection) against it. A pandemic can affect most countries and regions around the world. Health experts are concerned that the next flu pandemic could be caused by the H5N1 strain of the virus. Aflunov was expected to provide protection against this strain, so that it could be used before or during a flu pandemic.

Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against a disease. When a person is given the vaccine, the immune system recognises the parts of the flu virus it contains as 'foreign' and makes antibodies against them. The immune system will be able to produce antibodies more quickly when it is exposed to flu virus of the same strain. This helps to protect against the disease.

Aflunov contains small parts of the H5N1 strain of the flu virus. The virus used in the vaccine was first inactivated (killed) so that it does not cause any disease. Then, the outer membranes that contain the 'surface antigens' (proteins on the outer membrane of the virus that the body recognises as foreign) were extracted and purified before being included in the vaccine. Aflunov also contains an 'adjuvant' (a compound containing oil), which is expected to stimulate a better response.

The effects of Aflunov were first tested in experimental models before being studied in humans. The main clinical study of Aflunov involved over 4,000 adults. It compared Aflunov's safety and its ability to stimulate the production of antibodies ('immunogenicity') with those of a similar vaccine against seasonal flu. The comparator vaccine contained different strains of seasonal flu virus, but the rest of the components were the same as in Aflunov.

The application was at day 190 when the company withdrew. After the CHMP had assessed the responses from the company to a list of questions, there were still some unresolved issues outstanding. The CHMP normally takes up to 210 days to evaluate a new application. Based on the review of the initial documentation, the CHMP prepares a list of questions at day 120, which is sent to the company. Once the company has supplied responses to the questions, the CHMP reviews them and may, before giving an opinion, ask any remaining questions at day 180. Following the CHMP's opinion, it usually takes around two months for the European Commission to grant a licence.

Based on the review of the data and the company's response to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Aflunov could not have been approved for the prophylaxis of H5N1 avian influenza.

The CHMP was concerned over the way the main clinical study was carried out. An inspection of some of the study sites showed that the study had not been conducted in compliance with 'good clinical practice' (GCP). Consequently, the study results could not be considered reliable and could not be used for the evaluation of the vaccine. As a result, the size of the clinical database for the assessment of the vaccine's safety was not sufficient to fulfil the requirements of the EMEA's guidelines on prepandemic vaccines.

Therefore, at the time of the withdrawal, the CHMP could not conclude on the benefit-risk balance of Aflunov.

The letter from the company notifying the EMEA of the withdrawal of the application is available below.

The company informed the CHMP that there are no consequences for individuals currently included in clinical trials with Aflunov. If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.