© Remy Gabalda
The Levothyrox case? “There is no scandal”, the Minister of Health, Agnès Buzyn told us forcefully in September 2017. “It is a crisis linked to a lack of information and a lack of support, which must be understood. The new formula is even much more stable than the previous one. ” Dominique Martin, then director of the National Medicines Safety Agency (ANSM), told Release, in the same era : “A lot of information has been provided to health professionals. And yet, it didn’t work. The information did not get to the patients. This has generated a legitimate concern. It is a bankruptcy of our information system because the conditions for dialogue between the patient and his doctor have not been found. ” As for Merck, the laboratory repeated that the new formula was absolutely substitutable for the old one. And in addition if the company had made this change, it was at the request of the health authorities for the new drug to be even more stable… Final, peremptory remarks.
Formula change without validation
Words that prove to be inaccurate, even false, as detailed in the report of a forensic expert report, made public this weekend, requested by the examining magistrate after the complaints of several thousand patients, victims of related side effects to this new formula. This long report causes a feeling of despair, as we have the feeling that nothing has changed since the Mediator affair. Luckily, there were no deaths, and the side effects caused by the new formula were painful, but rarely very serious.
Let’s resume. Carried out at the request of the French Association of Thyroid Patients (AFMT), this expertise details the so-called Levothyrox case, this drug used by more than 3 million people in France to stabilize their TSH level, a hormone that stimulates the thyroid. In 2017, while the old formula had worked for years without causing side effects, the Merck laboratory brought a new formula to the market. He changed what are called excipients, this substance that goes into the composition of a drug and which serves to incorporate the active ingredients. By choosing mannitol and citric acid rather than lactose… For the good of the patient, Merck said in unison like the Medicines Agency, both emphasizing the desire for a more stable product. Why not ? But still it would have been necessary to carry out studies demonstrating the neutrality of these changes. However – and this is what the experts’ report confirms – this has not been done.
“The analysis techniques, used by the Merck laboratory, and validated by the ANSM, did not make it possible to demonstrate the physicochemical incompatibilities of the new excipients, mannitol and citric acid, with levothyroxine.” Worse, “well-known thermal analysis techniques made it possible to demonstrate these physical interactions with LT4 and their impact on resistance to dissolution, bioavailability and intestinal absorption. ” They have not been made. It was therefore not possible to say, as Merck and the ANSM have always said, that the new formulation of Levothyrox is interchangeable with the old one for all patients. “There was no guarantee that the direct substitution of the old formula for the new one would not cause any side effects, whatever the clinical situation of the patient.” In short, the change in formula was made without any serious scientific validation. And it is directly responsible for thousands of side effects that have nothing to do with any nocebo effect (1).
“In the end, it is the patients who clink glasses”
Doctor Philippe Sopena, general practitioner and former founder of the MG France union, is now an advisor to the AFMT association. He looked at this issue at length, as he saw patients arriving in his office unsettled by this new formula. “What happened is mind-boggling, he sums up. This new formula has never before been tested on the slightest patient, while we know that for the thyroid the question of dosage is important and delicate. This lightness is incredible. ” Then: “With the new excipients, the report shows us multiple interactions, and the impurities they produce have not even been explored. Experts note that Merck did not even take into account some conflicting results between the old formula and the new formula. “ Finally this observation, overwhelming in his eyes for the Agency: “Experts show that the ANSM has turned a blind eye to these shortcomings. Why ? Hopefully the criminal investigation will show it. The minimum prudence on the part of a so-called health security agency would have wanted it to have its laboratories validate the absence of impact of these modifications. And no. And what happened ? The ANSM has never ceased to praise the best quality and the greatest stability of the new formula. ”
One could smile at so much laissez-faire. And so-called communication errors have a good back. This case, which arises after the Mediator, leaves you speechless. How is it that in France in terms of drugs scandals follow one another? Should it be noted that at the same time the director of the Agency was seated in the dock during the Mediator trial? In fact, after the runaway moment, everything repeats itself, as Professor Bernard Bégaud noted in his book France, sick of the drug. “We still do not understand the reasons that led to switch from an old formula of Levothyrox which worked very well to a new one which was uncertain”, the latter also told us. “In the end, it is a caricatural example of these confused links between Big Pharma and health authorities”, concludes Dr Philippe Sopena for his part. “The Agency has not played its part. The minister supported the Agency, and in the end it is the patients who toast. As for the great doctors who said it was all due to a nocebo effect, they would do well to acknowledge their mistakes. ”
(1) Negative psychological effect associated with taking an inert substance.