During the health crisis, France not only failed to develop a vaccine. We know it less, but it also missed the development of another major prevention strategy, monoclonal antibodies. These treatments with unpronounceable names (sotrovimab, tixagévimab/cilgavimab, etc.) made it possible to protect patients who responded poorly to vaccination, but it was American and British companies that were leaders in this field. However, this was not inevitable.
The recent success of another drug from the same family, Beyfortus, which immunizes newborns against the bronchiolitis virus, gives new hope that France will focus more on this technology in the future. An imperative for Professor Brigitte Autran, president of the Committee for Monitoring and Anticipation of Health Risks (Covars), who calls for not repeating the – numerous – errors made in this area in our country during Covid. Because these treatments could prove very useful in the event of a new pandemic. Interview.
L’Express: The use of monoclonal antibodies as a strategy to combat infectious diseases remains relatively poorly understood. What are these products?
Professor Brigitte Autran: These are antibodies developed from white blood cells extracted from the blood of patients convalescing from an infection. B lymphocytes capable of producing antibodies with the best neutralizing powers against the target pathogen are selected from these globules, then they are purified and produced in large quantities. Depending on the form given to them, they will have a fairly long duration of action, from one to six months. They can replace vaccination, for example when there is no vaccine yet, as is the case for bronchiolitis in children. In the case of Beyfortus, manufactured and marketed by Sanofi, we do not block the infection, but we prevent severe forms which take children to intensive care. France is the country that purchased the most as soon as it arrived on the market, for the 2023-2024 winter campaign. This allowed us to demonstrate that real-life results were as good as during clinical trials. This will undoubtedly give a boost to these prevention strategies.
Covid had shown that monoclonal antibodies could also be very useful against emerging viruses…
The demonstration had already been provided in the context of the Ebola epidemic. The big advantage of monoclonal antibodies compared to vaccines is that they offer immediate protection, unlike vaccination, with which it generally takes two to three weeks for the body to start producing its own antibodies.
From the moment we can collect blood from convalescent patients, it takes around three months to develop these treatments: it is also much faster than other families of antivirals, which are based on chemical molecules. They therefore prove to be very useful when you have to move quickly, as was the case with Ebola. Against this virus in particular, scientists are now looking at whether it is possible to combine vaccination and antibodies, to have both immediate and lasting protection.
With Covid, we were able to protect the entire population with effective vaccines, and monoclonal antibodies found their place to protect subjects who responded poorly to vaccines. The only big downside is that with the arrival of variants, the first generations of antibodies gradually lost effectiveness.
The monoclonal antibodies used during the pandemic were all developed and produced abroad. Why has France failed to position itself on this strategy?
France has academic laboratories capable of developing monoclonal antibodies. We have the know-how, and it is a strategy in which we must invest, for emergency situations and perhaps also for other pathologies, as has just been demonstrated with bronchiolitis.
During the health crisis, very good antibodies were developed at the Pasteur Institute, but then there were blockages. It was very difficult and time-consuming to create a biotechnology company to exploit this discovery. When this biotech and the antibodies were industrially ready, the epidemic was almost over. Similarly, researchers from the Ecole Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI) also developed a monoclonal antibody in partnership with MIT in the United States, and they sought to sell their product to a large foreign pharmaceutical laboratory.
Since the chemistry of antivirals is not very developed in France, it would really be in our interest to rely on this know-how of monoclonal antibodies.
More concretely, what was the origin of these blockages, and how can we get around them in the future?
Monoclonal antibodies have become very important therapeutic tools for cancers and autoimmune diseases, and production capacities are growing globally. Moving from academic discovery to industrialization is therefore possible provided that there are no very heavy regulatory and administrative barriers which complicate this transfer.
Once an antibody is isolated and its effectiveness has been demonstrated, it must be patented very quickly, then settle the question of intellectual property in order to find investors who agree to finance the production of a clinical batch for the therapeutic trials, then to finance production on a larger scale. This entire chain must be thought out upstream and made more fluid, so that it is possible to be reactive during the pandemic.
Other countries have been able to do it…
In the United States, the Regeneron company capitalized on the know-how acquired during the Ebola epidemic. They put all their capabilities into the battle, with the support of the American government, and were able to very quickly develop excellent antibodies. AstraZeneca and GSK have also capitalized on their know-how in immunology. In France, unfortunately, the clinical development of the antibody from the Pasteur Institute arrived too late to involve the large pharmaceutical companies.
But in anticipation of the next crisis, it is essential that public authorities work upstream on the means of collecting blood donations from convalescent patients, and on the capacity to quickly mobilize this innovation chain.
Could monoclonal antibodies be useful in the case of a bird flu pandemic, for example?
If the avian flu virus ever mutated and became transmissible in humans, we would very quickly have vaccines. Several large laboratories already have candidates that they could quickly modify depending on the sequence that emerges. And we already have antivirals against the flu. Monoclonal antibodies could be an interesting complementary strategy, but it would probably not be a priority for this virus in particular, because it is very expensive and we are not completely helpless.
On the other hand, antibodies could be very useful in the event of an epidemic of chikungunya, West Nile fever, or other pathogens for which we currently have no other therapeutic means, such as West Nile fever. Rift Valley or Crimean-Congo fever, whose symptoms are similar to Ebola. Without forgetting of course the famous disease [NDLR : un terme de travail utilisé par l’OMS pour qualifier un agent infectieux capable de provoquer une pandémie grave, encore inconnue] against which we must also be prepared.
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