Mediator, an antidiabetic drug marketed by the Servier laboratory, was withdrawn from the market in 2009, presumed to be the cause of serious heart damage. The death toll is estimated at between 500 and 2,000 people. Chronology, results of the trial… A look back at the Mediator scandal.
Back to a widely publicized case. For 33 years, from 1976 to 2009, the Mediator®, marketed by Servier laboratories, has received marketing authorization in France. This medication was indicated for people with overweight with type 2 diabetes. However, this treatment with anorectic properties (reduces appetite) has mainly been diverted and prescribed as an appetite suppressant to 5 million people. He would have led the deaths of 1,000 to 2,000 people in France because of its increased risk of heart valve disease. On March 29, 2021, the Paris court rendered its judgment and sentenced Servier laboratories to 2.7 million euros fine for “aggravated deception” while having “knowingly concealed “appetite suppressant” properties and dangerous side effects“medicine.”Despite the knowledge that they had of the risks incurred for many, many years, (…) they never took the necessary measures and thus deceived” the consumers of the Mediator, declared the president of the correctional court, Sylvie Daunis, according to remarks reported by The Parisian. The group was nevertheless acquitted of the offense of fraud. Note that the movie “The Girl from Brest” by Emmanuel Bercot is the film adaptation of the book Mediator 150 mg by Irène Frachon, the whistleblower. What should we learn from this health case? Answers in 5 key points.
Marketed on the French market since 1976 and manufactured by Servier laboratoriesthe Mediator® is a drug composed of benfluorex, an active molecule aimed primarily at reducing the lipids (triglycerides and/or cholesterol) circulating in the blood. It was then indicated for overweight patients with type 2 diabetes according to its marketing authorization. Benfluorex is a hypoglycemic molecule, that is to say that it promotes the synthesis of glycogen by the liver and therefore has the power to reduce the level of sugar in the blood. Three pharmaceutical specialties based on benfluorex were then marketed in France:
- Pick® (1976-2009).
- Benfluorex Mylan® 150 mg (generic) (released in October 2009 and withdrawn the following month from the market)
- Benfluorex Qualimed® 150 mg (generic) (released in October 2009 and withdrawn the following month from the market).
This is the Servier laboratory.
Authorized on the French market for diabetics and people suffering from hypercholesterolemia, the Mediator® would have been diverted from this use and prescribed to other patients (non-diabetics) as an appetite suppressant to help them lose weight. But the benfluorex causes the production of norfenfluramine in the bodyan anorectic substance (hence the effects on weight loss) that is one of the amphetamines. A substance that is found in two other drugs from Servier laboratories: Isomeride® and Ponderal®. Appetite suppressants withdrawn from sale in 1997 because they had serious side effects (pulmonary arterial hypertension responsible for heart failure). These serious health effects were demonstrated in a study conducted in 1995 by Pr Abenhaim, with the team of pulmonologists at Béclère hospital (Clamart).
The Mediator was withdrawn from the market in 2009 due to an increased risk of heart valve disease.
Thirty years after its marketing, the Mediator® is therefore also suspected of increasing the risk of heart valve disease.
- In 1999 he is withdrawn from the market in Italy because of its health risk. The High Authority for Health (HAS) decides against the reimbursement of the Mediator, judging that it is of no medical interest.
- In 2003 he is withdrawn from the Spanish market.
- In 2007, the French Agency for the Safety of Health Products (Afssaps, now ANSM) recommended that it no longer be prescribed as an appetite suppressant.
- In 2007Irène Frachon, pulmonologist at Brest University Hospital, launches the alert on the dangers of the Mediator, after investigating its cardiac effects for 10 years. It reports cases of heart valve disease to the Medicines Agency. Two years later she would publish the best-selling book “Mediator 150g, how many deaths?“.
- On November 30, 2009, the Mediator and its credits are withdrawn from sale in France by Afssaps. The truth breaks out in the press and the affair turns into a health scandal. Xavier Bertrand, Minister of Health at the time, wanted all patients who had been treated by the Mediator to consult their doctor. A total of 5 million people have used the Mediator® in France between 1976 and November 2009.
Who is Irène Frachon, the whistleblower?
Born March 26, 1963 in Boulogne-Billancourt, Irène Frachon is a pulmonologist at Brest University Hospital and launched the alert on the dangers of the Mediator in 2007, after investigating its cardiac effects for 10 years. She reported cases of heart valve disease to the Medicines Agency and two years later published the best-selling book “Mediator 150g, how many deaths?“.
The film The Girl from Brest, directed by Emmanuel Bercot, is the adaptation of the book by Irène Frachon. He came out on November 23, 2016 in France. Sidse Babett Knudsen plays the role of Doctor Irène Frachon and Benoît Magimel plays the role of Pr Antoine Le Bihan.
What are the side effects of Mediator?
Norfenfluramine increases the risk of heart valve disease i.e. heart valve dysfunction which are 4 in number: the aortic, mitral, tricuspid and pulmonary valves. These heart attacks are sometimes painless and can go unnoticed for years. But sometimes, symptoms are present: heart failure, shortness of breath on exertion, pulmonary edema… A diseased heart valve is fragile and very susceptible to infection. Cardiac damage is not the same for all patients and also depends on how long the Mediator is taken.
The number of deaths is estimated between 500 to 2,000 people
How many deaths are there in France?
In 1999, a first case of heart valve disease is reported in a person using the Mediator. Ten years later, the Afssaps estimates that 500 deaths are attributable to taking this anti-diabetic. On January 16, 2011, the General Inspectorate of Social Affairs (Igas) submitted its report to the Ministry of Health and concludes that the number of deaths is estimated between 500 and 2,000 people. In August of the same year, an investigation opens in Paris for “aggravated deception”, “illegal taking of interest”, “involuntary homicides and injuries” and “scam”. The National Office for Compensation of Medical Accidents received a total of more than 9,000 compensation claims.
What are the results of the trial?
Ten years after the revelation of this health scandal, the Mediator trial opened on Monday, September 23, 2019 at the Tribunal de Grande Instance of Paris. The defendants, namely executives from the Servier laboratory and the Medicines Agency, were tried for aggravated deception with endangering health, fraud, manslaughter and involuntary injury and influence peddling. The Servier laboratories were suspected by the examining magistrates of having concealed the pharmacological reality of the Mediator, whereas two of their products had however been withdrawn from the market in 1997 for “extreme precaution”. However, the Servier group claims that it was unaware of the toxicity of their product and that nothing, before the withdrawal on the market of the Mediator proved its dangerousness. He concedes not having “perceived the level of risk as he should have” and “made a parsing error“, reported AFP on Tuesday, December 3, 2019. However, Emmanuel Canet, representative of Servier assures that the group had absolutely no “the desire to deceive or conceal” consumers or healthcare professionals.
On his side, the ANSM is judged for “negligence”, for having delayed in suspending the marketing of the Mediator and for having had “ links of interest with the Servier group”. Irène Frachon must take the stand as a witness. Until April 30, 2020the date on which the trial is due to end, thousands of plaintiffs await “answers and reparations”.
► Result of the trial: on Monday March 29, 2021, i.e. 11 years after the end of the marketing of the Mediator and more than 517 hours of hearing, the Paris court delivered its judgment and sentenced the Servier laboratory to 2.7 million euros fine for “aggravated deception”. “Despite the knowledge that they had of the risks incurred for many, many years“, the firm would have favored “his financial interests“to the detriment of”drug consumer health“. The former number 2 of the Servier group was given a 4-year suspended prison sentence. The pharmaceutical group was however acquitted of the crime of fraud. For its part, the Medicines Agency (ANSM) was sentenced to 303,000 euros fine and will not appeal this decision, she specifies in a statement of March 29, 2021.
The ANSM was created in 2011 by law, in response to the tragedy of the Mediator, as part of a legal continuity with the Afssaps. This new structure, which has therefore replaced the Afssaps, is primarily intended to strengthen health security so that such a case cannot happen again. |
Sources: Survey on the MEDIATOR® of the General Inspectorate of Social Affairs (January 2011); Letter to AFSSAPS patients and ANSM press release on the Mediator trial; Reports of the joint fact-finding mission on the Mediator available on the Senate website (2011).