EMA says link between narcolepsy and Pandemrix 2009 H1N1 vaccine exists

By Dr. Ananya Mandal, MDJul 21 2011

A final review result from Europe's drug regulatory agency released a positive link between narcolepsy and the Pandemrix 2009 H1N1 vaccine. The agency recommends a labeling change that limits the vaccine's use in children and teens to when protection is needed and seasonal trivalent vaccine isn't available.

The link was primarily reported from Scandinavian countries between the vaccine and narcolepsy in young people. Pandemrix, made by GlaxoSmithKline (GSK), is one of the 2009 H1N1 vaccine used in Europe during the pandemic, and it's unclear how many doses are still on the market. It contains the AS03 adjuvant.

So far 31 million doses of Pandemrix have been administered in 47 countries, GSK said. It has received 335 reports as of Jul 6 of narcolepsy in people who were immunized with Pandemrix, of which 68% were from Finland and Sweden.

The European Medicines Agency (EMA) said today in a press release that its Committee for Medicinal Products for Human Use (CHMP), however, has confirmed that the vaccine's overall risk-benefit balance is positive. The EMA said, “in persons under 20 years of age Pandemrix may only be used if the recommended seasonal trivalent influenza vaccine is not available and if immunisation against H1N1 is still needed (e.g., in persons at risk of the complications of infection).”

The review was undertaken by the CHMP in August 2010, based on a request from the European Commission. Today's labeling change recommendation follows an interim one in April asking GSK to warn about the risk in young people and advise healthcare providers to perform an individual benefit-risk assessment before administering Pandemrix.

The EMA for this recommendation took into consideration epidemiologic studies conducted in Finland and Sweden, safety and surveillance data from several other EU countries, and preliminary findings from an eight-country study coordinated by European Centre for Disease Prevention and Control (ECDC). It also incorporated feedback from an expert meeting that discussed that link. The EMA said the Finnish and Swedish studies were well designed, showing a 6- to 13-fold increase risk of narcolepsy in young people who had received the Pandemrix vaccine. It added that link has not been found in adults 20 and older.

The vaccine likely interacted with genetic or environmental factors that could boost the risk of narcolepsy, the EMA said, adding that several studies in the European Union are under way to explore other possible connections.  “Exposure to specific infectious diseases (including H1N1) at different ages, particularly upper respiratory infections, may have contributed to the observations in the Nordic area.” More research was necessary the EMA said.

An MHRA spokesman said, “The regulatory action for Pandemrix vaccines recognizes the potential seriousness of H1N1 infection and ensures the vaccine remains a licensed alternative to protect children. However, as the shelf-life of remaining UK stocks of Pandemrix expires in October this year, the vaccine will not be used in the 2011/12 flu vaccine campaign.”

GSK said in a statement today that the labeling change will replace the advisory to clinicians that the EMA recommended in April. The company said it would continue to work closely with the EMA and other regulators to explore the possible link. The company also said it will conduct more research on the possible link and include input from independent experts, per an agreement with the EMA.