CELL THERAPIES, gene therapies, tissue engineering products. Complex therapies, to which the definition of drug is narrow. In fact, we call them, more properly, advanced therapy medicinal products (ATMP) and, far from being a promise of medicine, they are already therapies on the market. In Europe there are 15 active ones: they are used to treat some forms of tumors, retinal diseases, haemophilia and immunodeficiencies. And many, likely, will come, considering that at the moment there are almost a thousand clinical trials involving advanced therapies. The numbers are contained in the 5th Italian report on advanced therapies produced by the ATMP Forum, presented today in Rome, which took stock of active trials, regulatory status, but above all on the challenges that await us to make them available to patients. First of all, those of sustainability, because these therapies cost, and a lot: in the order of hundreds of thousands of euros, up to two million euros. A cost too high to be unsustainable even for manufacturing companies in some cases, especially when it comes to rare and ultra-rare diseases where patients are very few.
Advanced therapies for rare diseases: the retreat of companies
In fact, part of the new advanced therapies will also concern rare diseases, especially in the area of onco-hematology and ophthalmology. On the other hand, rare diseases have led the way in the field of advanced therapies: the first approved gene therapy drug in the world was Strimvelis, indicated for the treatment of congenital immunodeficiency ADA-SCID. Yet, due to a bizarre law of retaliation, they are the ones who risk being the first to leave. It has already happened in reality: BlueBird Bio has done it in Europe with gene therapies against beta-thalassemia and cerebral adrenoleukodystrophy. Orchard Therapeutics did this with Strimvelis, now “saved” by the Telethon Foundation – in whose laboratories the drug was born – to ensure that it is still available to patients. Few economic returns, no agreements to support research costs. But rescue by foundations cannot be the solution: it is necessary to rethink the system so that it can be sustainable, and to guarantee in return availability to all patients who need it. All the more so considering that more and more advanced therapies could come, and not just for rare patients. Overcoming the ideological alignments that see the industry as thirsty for money and the regulators too rigid, as told by Francesca Pasinelli, general manager of the Telethon foundation.
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Taking out of the industries (part of) the development of therapies
“One of the proposals that we as Telethon put forward is to work very intensely on the optimization of development paths, starting from the research conducted in the academy – explains Pasinelli – especially considering that almost all these therapies are born within the academy. But once the therapeutic strategy has been identified, the academy leaves the development part in charge of the company that licenses the product ”. But a new development model is possible, for example by enabling the academy to work at the very early stages of development: “I am thinking, for example, of conducting preclinical efficacy and toxicology studies, according to the GLP (Good Laboratory Practice, nda) criteria. , allowing the collected data to be included in a regulatory dossier. If this does not happen, the data cannot be useful for regulatory purposes and therefore must be repeated, and this increases the development cost “. On the contrary, at the Telethon institutes, pre-development structures are already in place which make it possible to license products to companies with data that can already be included in regulatory dossiers. “The same goes for GMP (Good Manufacturing Practices) production facilities: at this moment there are no academic or public, or non-profit, manufacturing facilities, or they are few”.
If until a few years ago similar speeches might have seemed premature, the arrival of advanced therapies, the multiplication of field studies, the always problematic node of price negotiation between companies and payers, now makes it necessary to rethink the entire system. It is a valid discourse in general, but above all for Italy, which, although at the forefront for the development of advanced therapies, has not been able to grasp the arrival of these opportunities and also this risk and has not adapted, Pasinelli continues. : “The same has not happened elsewhere. For example, the Catapult project was launched in Great Britain, a large public-private operation to systematize all the skills to activate the production sites that can also be accessed by academies, the regulatory skills to facilitate the development of therapy from the beginning. therapy. It is not just a matter of organization: a similar system helps to reduce development and production costs, because there is no risk of replicating data already collected and there is no involvement of industry alone. Ultimately, this also helps to negotiate a lower price and at the same time become the owners of some know-how in the field, not to be mere payers ”.
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Alongside solutions that Pasinelli calls “system” there are also more practical solutions to shorten the development paths of advanced therapies, as also discussed in a recently published paper in Nature Medicine together with Luigi Naldini and Alessandro Aiuti of the San Raffaele Institute -Telethon for gene therapy. “For example, for the gene therapies we developed in our institute we worked according to rules that required for each product to repeat common steps. We had to do it because not much was known. But now we believe we have reached a point where it is necessary to rethink this model and we are starting to propose, with the regulatory authorities, a path that instead of operating in series works in parallel for different diseases, with adjustments for individual diseases but exploiting common elements. and minimizing the numbers of experiments “.
The speech of the DG of Telethon is an appeal not to waste resources and avoid the multiplication of processes, experiments and paths. Even when you pass from laboratory studies to real therapies. As you can read in the chapter signed by him in the ATMP forum report: “It is desirable that a centralized European fund be established for the purchase of ATMP for ultrarare diseases and that it focuses on policies aimed at facilitating cross-border patient transfers towards the few specialized centers for the administration of these therapies “.