Smart Pharmacy

Immunotherapy arrives on the market
In this new way of healing, the closest technologies to the market are those of immunotherapy. From gene therapy, they involve modifying the cells of our immune systems to recognize and attack the cancerous tumors that usually escape them. Or to weaken the defenses of tumors that serve to hide them. Mainly used in oncology, they have been effective on certain cancers deemed incurable (see "Ending cancer", page 6). For Laurent Alexandre, president of DNAVision [and minority shareholder of La Tribune, ed], "it is the pleasant surprise that we did not expect and the most successful technology is that of CAR-T. It must be said that in oncology, courses are faster to reach the market. With terminally ill patients, for whom no chemo or radio has been effective, health authorities are willing to take risks with new molecules. And some are very effective, "says the author of the best-selling book Death of Death (Lattes, 2011). Since the first Opdivo, authorized in June 2015 and bought by Bristol-Myers Squibb (BMS), other treatments have arrived on the market such as Keytruda (Merck) for lung cancer.

Breakthrough therapies on production and prohibitive prices
But if the first rays of sun in the world of immunotherapy announce the spring, it will be necessary to wait for the summer. Explanations: Since our immune system is programmed to attack all living cells that do not have exactly the same DNA as it, one of the limits of these biotherapies is that of tolerance. As with transplants, the body tends to reject them without giving them time to heal. This is why a majority of developments focus on the patient's cells (called autologous cells). These cells are removed and corrected to no longer make us sick or to attack cancerous tumors, changes often made using the new CRISPR-Cas9 biological slide. They are then assembled with other biological elements necessary to form drugs, then cultured before being reinjected to the patient. To manufacture them avoiding any contamination or genetic mutation, the high protection techniques of laboratories are sufficient. But - problem - go into industrial mode is not obvious: these custom treatments are necessarily small quantities, production costs are exploding and tariffs are blazing. In addition, as most of them concern rare diseases and a limited number of patients, profitability is even more difficult to achieve.

In gene therapy, the first treatments marketed record prices such as one million euros for the Glybera, $ 594,000 for Strimvelis baby "bubble" and $ 850,000 for the Luxturna Spark, against the degeneration of the retina. Outstanding prices that caused Glybera to be taken off the market due to a lack of sales and which greatly limited the success of Strimvelis. Today, some work on cells that can tolerate or survive long enough to educate the immune system before being eliminated. Objective: Generic formulas suitable for industrialization. This is the case of Cellectis with provisional T-CARs and the Eukarys seedling, with its synthetic gene therapy treatment delivering its instructions only during the period necessary to correct the problem, before disappearing.

What must USA do to stay in the race?
And the Hexagon in all this? If she stays far behind the American giants Spark Therapeutics, Bluebird Bio or Sangamo Bioscience, she still has some strengths. She remains one of the pioneers of gene therapy, thanks to the work funded by the Telethon. Alongside the United States, it is the only country to have two of its laboratories ranked among the top 10 global centers for health research (with Inserm and AP-HP). Among the promising developments, Inserm has created the creation of Brainvectis, a startup implanted at the Brain Institute of La Pitie Salpetriere.

As Jérôme Becquart explains, "Brainvectis is developing gene therapy to restore the metabolism of cholesterol in the brain, a pathway deficient in a number of neurodegenerative diseases, such as Huntington's disease or Alzheimer's disease. But USA also has weaknesses. On the one hand, our country, which missed the turn of the monoclonal antibodies, is not yet developed on bioproduction. "We lack major bioreactors and some young shoots are now buying their antibodies to Chinese biotech Wuxi, which has been well placed on the European market," said Maryvonne Hiance, President of France Biotech. For laboratory tests, small specialized cell production units exist, particularly around Nantes, which could qualify as "Cellular Valley".