At the Mediator appeal trial, the representative of Servier laboratories and the group's former number 2 denied on Tuesday any desire to minimize the risks of the drug and assured that they had not had a "feeling of alert" before its
. in 2009.
Obviously today, a posteriori, with everything we know, it may seem surprising
”, concedes before the Paris Court of Appeal Isabelle Tupinon-Mathieu, who represents Servier.
But let's go back to the time (...) At Servier, we don't have this feeling of risk, of alert
", assures the trained rheumatologist, who warns against the "
bias of retrospective rereading and anachronism
The second French pharmaceutical group and its former general manager Jean-Philippe Seta have been retried since January 9, in particular for aggravated deception and homicides and involuntary injuries.
The Mediator, marketed as an antidiabetic since 1976 and wrongly prescribed as an appetite suppressant, has caused serious cardiovascular effects in thousands of patients and many deaths.
First instance judgment
At first instance, in March 2021, the Paris Criminal Court found that the Servier laboratories “
had from 1995, enough elements to become aware of the fatal risks
” linked to the Mediator.
The drug agency (Afssaps, now ANSM), found guilty of having taken too long to act, did not appeal.
In 1995, a study concluded that two appetite suppressants from Servier, Isomeride and Pondéral, increased the risk of pulmonary arterial hypertension (PAH), a rare and very serious disease.
For the prosecution, Servier should have alerted the authorities to the chemical relationship of Mediator with these drugs, banned in 1997. Once ingested, all three lead to the formation of the same molecule, a derivative of amphetamines toxic to the lungs and valves cardiac.
Suspicions not shared
The health authorities had “
all the information
” on the presence of this molecule, called norfenfluramine, maintains Isabelle Tupinon-Mathieu, long director of therapeutic research at Servier.
In addition, "
the chemical structure, in itself, does not predict (...) the potential deleterious effects
", she observes, giving the example of very similar drugs but which do not cause the same side effects.
at the time, there was nothing that pointed to norfenfluramine as being responsible for valvulopathies and PAH
", she stated, questioned about an internal Afssaps report from March 1999 which evoked a concern linked to this molecule.
In October 1999, an Italian report concludes with “
suspicions that patients treated with benfluorex (the scientific name of the Mediator, editor’s note) are exposed to a potentially toxic level of norfenfluramine
And in December 2000 a scientific study demonstrated the toxicity mechanism of norfenfluramine in the appearance of valvulopathies.
It's not a certainty, it's a little more complicated than that
," says Isabelle Tupinon-Mathieu.
But as early as 1996, the Swiss health authority requested recent data from Servier, estimating that in view of "
the very similar structure
" of Mediator and Pondéral and as long as the risk of adverse effects is not excluded, it "
must consider that this risk exists
It constitutes a strong alert which should have led to more investigations
”, judges the Advocate General.
After the first two cases of PAH and valvulopathy declared in 1999, there will be "no
more case reports until 2003
", argues Isabelle Tupinon-Mathieu.
We can't say that we didn't worry about safety, that's not true
,” she defends herself.
Both Servier and the
the real significance of these cases, which appeared to be sporadic, isolated
, ”recognizes Jean-Philippe Seta, 69.
Clinical trial in 2005
When Servier finally launched a clinical trial on the Mediator in 2005, "
we still have great confidence both in the efficacy and in the safety of use of this drug
", assures the former manager.
I know it might look a little crazy with the eyes of 2023, but at the time it was the truth
The study will show in 2009 that patients treated with Mediator have a much higher risk of developing a heart valve leak than those who have taken another antidiabetic.
Despite these results, Servier will simply suggest that the Afssaps mention the risk in the drug's instructions.
The agency will decide for a ban.