It hasn’t happened for more than thirty years. For the first time since the invention of benzodiazepines and z-drugs (stilnox…), a new family of sleeping pills is about to hit the market. The first of these was authorized in the spring by the European Medicines Agency, and it is already available in Germany and Italy. In France, the Quviviq should be marketed from 2024, because the laboratory is just about to file its request for reimbursement with the health authorities.
On paper, this treatment is enough to change the lives of insomniacs: “Our product brings a new approach: it blocks the mechanisms of awakening, unlike current molecules which act more like anesthetics. In our studies, patients have almost the same sleep as normal sleepers, and they also say they feel better during the day,” says Jean-Paul Clozel, a Frenchman who co-founded Swiss-based biotech Idorsia with his wife Martine Clozel.
The couple is not unknown in the world of pharma: the Clozels have already made a fortune by selling their first company, Actelion, to the Johnson & Johnson laboratory in 2017. However, they had not transferred to the American giant their molecules still in development, and in particular this product against sleep disorders. It must be said that they had been working there since the early 2000s: “We had studied in California, and we knew the French people well who ran the sleep center at Stanford University. When Professor Emmanuel Mignot discovered the role of a protein called orexin, absent in patients suffering from narcolepsy, my wife immediately saw a new way against insomnia”, recalls the CEO of Idorsia.
A molecule that blocks the “protein of awakening”
It will prove “extremely long and difficult” to find the ideal molecule. It had to be able to pass the blood-brain barrier to come and block the receptors of this “protein of awakening”, that it be fast-acting so that it could be taken in the evening just before going to bed. , but with a time-limited effectiveness so that patients do not drowsy during the day. The Clozels will even have to abandon a first product along the way, before finally succeeding…
“It’s a real breakthrough, but when it happens, it’s going to be a tsunami in terms of prescriptions,” predicts Dr Isabelle Poirot. This psychiatrist, however, wants to be cautious: “If we do not work on the behavior and thoughts of patients in relation to their sleep, their insomnia is likely to persist, and they will be disappointed”, she warns. Same precautions of Pr Yves Dauvilliers, who participated in the development of clinical trials of Quviviq: “It is very important to take the time to question the patient. An insomnia consultation is 30 to 40 minutes. Associated pathologies, such as sleep apnea, restless legs syndrome, pain, anxiety or depression should be ruled out.And if there are too many cognitive or behavioral dysfunctions, if you ruminate, take alcohol, spend too much time in bed or on your screens, the medicine will not have the desired effect”. If necessary, the diseases should be treated, or behaviors modified, before prescribing this product. “And especially not to say: I give you this medicine and you will sleep well. It’s a figment of the mind”, insists Professor Dauvilliers.
A medicine that does not cure
In fact, it is the general practitioners who will probably be the first prescribers. With often too little time for such support. But Jean-Paul Clozel assures that his laboratory will take care of training them, and reminding them of these precautions: “Cognitive and behavioral therapies remain the first treatment against insomnia: when they allow patients to get back to sleep, it there is no reason to give them our product”, recognizes the boss of Idorsia. Because CBTs have an undeniable advantage: when they work, they provide lasting relief. While this drug does not cure: if the patient stops taking it, the disorder returns. “It’s a bit like when you have a toothache. You can take a painkiller, but you still have to go see a dentist to find out why you have pain,” said Dr. Marc Rey, president of the National Institute of sleep and alertness. “It is the first molecule that specifically attacks this hyperarousal suffered by insomniacs, but it does not act on the cause of the abnormal activation of the orexin system in these people”, recalls Pierre- Hervé Luppi, from the Lyon Neuroscience Research Center.
Finally, as with any new drug, it will also be necessary to see its effectiveness in real life, and to monitor the appearance of any unexpected adverse effects: “The clinical trials were well done, but they related to a still limited number of patients, within the very specific framework of a therapeutic protocol, for which they are carefully selected”, notes Isabelle Poirot. From this point of view, the French can be reassured: by 2024, the laboratory, and the health authorities, will benefit from the experience of the countries where Quviviq is already marketed.