Medicine of the person is one of the most interesting perspectives from which to look at medicine in the third millennium: a new paradigm in which the most effective solutions are sought for preventing, diagnosing and treating diseases based on the characteristics of the individual, such as genetics , the environment in which he lives and the lifestyle. All these important issues were addressed by the international conference "The Healthcare to come" promoted and organized by the Silvio Tronchetti Provera Foundation and the Umberto Veronesi Foundation, in collaboration with the State University of Milan. Meeting that attracted high-profile scientists and researchers from all over the world to the great hall of the university built in the former Ca' Granda del Filarete James Patrick Allison, Nobel Prize for Medicine 2018.
Developed on the thrust of genetics, genomics and other so-called "omics" sciences, personal medicine, like all precision medicine, is made possible thanks to the opportunities opened up by bioinformatics, nanotechnologies and the digital revolution. Thanks to these tools, in fact, today it is possible to manage an innumerable amount of data, explore in depth the characteristics of a large number of people, all in a short time. The hope is to be able to govern this complex system of knowledge to offer the most effective and safest treatments possible to a given patient at a given moment, avoid useless treatments and optimize prevention and early diagnosis approaches.
If up to a few decades ago the topic seemed futuristic, today the medicine of the person is a reality. The fields of clinical application are still limited but growing, research is in turmoil. Molecular targets are being studied for rare diseases and tumours, but also for autoimmune, neurological, psychiatric and metabolic diseases. And no less are the impacts that the medicine of the person can have, for example, on the sustainability of the health system.
"It is no longer just a pioneering subject: precision medicine enters an "adult" phase and is called to new tasks - he said Paul Veronesi, President of the Umberto Veronesi Foundation and Director of the Ieo Senology Program -. The mission of doctors and researchers is to find the best possible solutions and ensure that they are offered to all those who can truly benefit from them. A path that can take us far, but that must be taken step by step, without underestimating its complexity”. Also Marco Tronchetti Provera, president of the Silvio Tronchetti Provera Foundation, underlined in his speech at the opening of the conference how "the encounter between 'big data biology' and "big data society" made possible by digitization has allowed us to open new frontiers in this and we are proud to support the dialogue between the world's leading scholars of the subject for an indispensable comparison to address all the implications that the development of personalized medicine implies".
And the challenges opened up with "personalized medicine" find in oncology the discipline where this impact is already evident. “It proves it – he said Pier Giuseppe Pelicci, Director of Research and Chairman of the Department of Experimental Oncology Ieo and member of the Scientific Committee of the Umberto Veronesi Foundation – the introduction into clinical practice of numerous molecular therapies, including targeted-treatments and immunotherapies. Since the late 90s, unprecedented results have been achieved, with long-lasting effects and, in some cases, complete healing of various types of tumours. Now we need to increase the number of patients who can benefit from it, especially for that – prevalent – part that does not respond to immunotherapy”.
Since the first examples of personalized medicine in oncology in the late XNUMXs, many successful targeted treatments have been introduced and, more recently, immunotherapy with inhibitors of immune response blocking molecules (ICIs) has led to with unprecedented long-lasting effects and, in some cases, the complete cure of different types of cancers (such as melanoma, lymphoma, lung cancer and many others). Nonetheless, there is still room for improvement as most patients fail to respond to immunotherapy due to intrinsic disease resistance or the rapid emergence of resistant tumours.
Two luminaries of the University of Texas MD Anderson Cancer Center in Houston focused on the new therapeutic approaches in the pre-clinical and cynical phases in their reports: Padmaee Sharma, Professor in the Department of Genitourinary Medical Oncology, Division of Oncological Medicine, and Giulio Draetta Senior, Vice President and Head of Therapeutics Discovery, Division of Discovery and Platforms. Luigi Naldini, director of SR-Tiget in Milan, focused on cell and gene therapies which are becoming a new pillar of modern medicine and help us treat an ever-increasing number of human pathologies. In some strategies, hematopoietic stem cells are taken from a patient with hereditary immunodeficiency syndrome, genetically corrected ex vivo and infused back into the same patient to guarantee him/her the constant availability of functional progeny potentially for the rest of life; mature cells from different lineages can therefore fight pathological conditions such as primary immune deficiencies, blood disorders and storage diseases. In other strategies, lymphocytes are harvested from a cancer patient, expanded and engineered ex vivo to better fight the tumor, then infused back into the patient.
Italy has been at the forefront of the development of advanced therapy drugs, ATMPs, with three of the top four cell and gene therapies registered for the European Union and international markets coming from the national research pipeline.
For this reason, the stakeholders of the Italian biomedical community, the pharmaceutical industry and regulatory bodies have faced the challenge of planning for the first time a system for the production, clinical trials and, eventually, the commercialization of drugs deriving from ex vivo cultures and genetic modification of patients' cells, intended for one-time administration but with the potential to offer sustained therapeutic benefits – or side effects – throughout the patient's lifetime. Therefore, problems such as the definition and monitoring of the safety of ATMPs (acronym which stands for Medicinal products for advanced therapy) in the short and long term, the determination of their quality and possible dosages and their safe administration to patients had to be addressed. Furthermore, the costs and reimbursement methods for this kind of new drug had to be established for the first time.
“Although this experience has been gratifying from the point of view of the development of new and increasingly powerful drugs capable of combating serious pathologies still without a cure, we should ask ourselves what conditions have favored the virtuous circle of their development; what role academia, industry and regulatory bodies have played in charting the path that led to successful clinical trials and, consequently, to the commercialization of the first drugs of this kind.
Rare pathologies represented an ideal testing ground for the first ATMPs, but today we are faced with a rapid expansion of cell and gene therapies for the treatment of more common diseases such as cancer, and the question arises whether the paradigms that have allowed the early successful development of ATMPs for rare diseases are still valid, and how and to what extent their cost can be sustainable.
As more and more large pharmaceutical companies operate in this new sector, and as more and more ATMPs become available for an ever-widening range of pathologies, how will the clinical and regulatory landscape manage to adapt and change? And will these changes benefit patients or business interests more? How will we streamline the current regulatory framework for clinical trials of future ATMPs? How to ensure fair public access to these new treatments? Only collaboration between all stakeholders in the scientific, medical, pharmacological, decision-making, regulatory and awareness-raising fields, based on scientific evidence and inspired by the ethical principles of a just society, will allow us to face these challenges and to seize the promise of providing the long-awaited relief where the disease burden is still unsatisfied.
