Chronic drug shortages, orphan diseases, pandemic… Our needs for new treatments are constant and increasing, but they are increasingly difficult to meet. The reason: the shortage of certain active ingredients, the relocation of the pharmaceutical industry outside of Europe and the staggering costs of scientific research.
So, among the avenues of therapeutic innovation that bring hope, emerges the “repurposing” of drugs, or repositioning of molecules, which consists of reusing old drugs for new therapeutic indications. In short, we make something new out of something old, faster and for less money. But how does it work? Is it safe? What are the benefits of these initiatives and who funds them?
“The underrated champion of sustainable innovation”
The repositioning of drugs, the patent of which has generally fallen into the public domain, “aims to identify new uses of approved or experimental drugs which fall outside the scope of the original medical indication,” praises the World Medicines Organization. health (WHO). New treatments are sought mainly from products already in use.”
“Based on drugs that already exist and are widely used, their safety in humans has already been demonstrated, which makes it possible to skip the first stages of therapeutic trials,” explains Nathalie Coutinet, health economist and co-author of Economics of medicine (ed. La Découverte). This allows for therapeutic innovation at lower cost.”
At the end of the chain, “it’s a huge time saver, since the tolerance and safety of the reused drug have already been established,” says Frédéric Bizard, health economist and author of Solidarity autonomy in health (ed. Michalon). It remains to provide proof of its effectiveness in a new therapeutic indication. We then have tighter clinical development and above all production capacities ensured by production lines that already exist, which represents hundreds of millions of euros saved, he explains. “It’s a form of recycling of medicine in the general interest.” Moreover, the WHO is not mistaken, and sees the repositioning of medicines as “the underestimated champion of sustainable innovation”.
A new approach to incurable diseases
And this is already a reality for many drugs, which have proven themselves for pathologies other than those for which they were created. Among them, aspirin, an anti-inflammatory with analgesic properties, which has long also been used to prevent recurrence of myocardial infarction and stroke, thanks to its ability to thin the blood. “This is also the case for Thalidomide, indicated against nausea in pregnant women, this drug which caused congenital malformations was bought from the Grunenthal laboratory by the American biotech Celgene, which developed on the basis of this drug a treatment against myeloma and lymphoma, two forms of cancer, specifies Frédéric Bizard. Renamed Thalomid, it now brings billions of dollars in annual revenue to biotech.” Sometimes, the initiative turns into a fiasco, as with hydroxychloroquine, an antimalarial wrongly erected by Professor Didier Raoult as a miracle treatment against Covid-19.
But sometimes, the repositioning of drugs makes it possible to treat previously incurable diseases, opening up new hope for cure. In a study published in January 2020 in the scientific journal JAMA Dermatologya team of doctors from Necker hospital and researchers from Inserm described the remission of three children suffering from Olmsted syndrome. A rare disease for which there is no treatment, which appears in early childhood and “manifests itself as palmoplantar keratoderma, an impressive thickening of the skin of the palms and soles, extremely painful,” report the authors.
“These children have developed a strict inability to walk and sleep due to continuous pain, a depressive syndrome, a blocked puberty and a delay in growth,” describes Professor Christine Bodemer, head of the dermatology department at the Necker hospital. Doctors then turned to erlotinib, a cancer treatment that works by blocking the activity of a protein called epidermal growth factor receptor (EGFR), and which also targets the mechanisms of Olmsted syndrome. Result: “in less than 90 days, we observed an almost complete remission,” indicates Dr. Céline Gréco, pain doctor in Necker. The pain disappeared completely and the children began to walk, were able to return to school and return to life as normal teenagers.”
Stimulate research around repurposing
Thus, “it is often doctors who, in the context of their practice, discover that a drug can have beneficial effects for other indications, and this is where we wish to intervene,” explains Dr. Loïc Brotons, medical doctor. resuscitator anesthetist and general director of Galeon, a start-up specializing in artificial intelligence in health, and Matthieu Gueniffey, vice-president. Because laboratories and venture capitalists [qui financent les start-up] are looking for higher-yielding projects, often they are not interested in these older drugs that they consider less profitable.”
To stimulate research in the field, the start-up is launching its very first call for projects campaign this Wednesday. “It is intended to encourage all caregivers, who have documented intuitions about a drug that could be repositioned, to submit their observations thanks to a form accessible online, explains Loïc Brotons. Then, an independent council will analyze all the projects submitted and select a drug, for which we will finance trials to the tune of 500,000 euros, carried out by specialists in the disciplines involved. This may concern all drugs that have fallen into the public domain, for all types of pathologies.” Their goal, “non-profit and without any compensation: to rely on human intelligence to support medical research and open the way to innovative treatments for all”.
A solution for the future, believes Frédéric Bizard: “the technological revolution driven by biotech is formidable, but when we look at the cost of new molecules and the curve of aging in poor health with the very sharp increase in chronic pathologies, it is obvious that we will be unable to pay the price of these high-cost innovations for everyone. We must not only act on prevention, but also on these less costly therapeutic innovations. Old molecules which, thanks to their safety and clearly established effectiveness, should obtain their validation even more quickly by the French and European drug agencies for their new therapeutic indication.” This is also one of the challenges of the reform of EU pharmaceutical legislation presented in spring 2023, which aims to “remedy shortages of medicines and guarantee security of supply”, by encouraging laboratories to focus on repositioning and allowing doctors and researchers to submit marketing applications.