Spain approves the use of CAR-T, the first public immunotherapy against leukaemia in Europe

Santa Coloma de GramenetTen years of research and over 6,000 pages of information that support its quality, safety and efficacy confirm that immunotherapy with CAR-T will be the treatment of the future for the most resistant leukaemia in Catalonia and Spain. A future that is becoming more and more immediate, since the Spanish Agency of Medicines and Health Products (Aemps) has authorised this Wednesday the exceptional and hospital use of CAR-T ARIO-0001 in severe patients with acute lymphoblastic leukaemia. This promising gene therapy is based on the laboratory modification of the lymphocytes in charge of the immune response to make the body react and attack the tumour cells on its own. It is estimated that at least 25 people with leukaemia who do not respond to conventional treatments could be treated annually at the Hospital Clínic in Barcelona, which has developed this personalised medicine. For the time being, patients will have to be over 25 years old.

Hospital Clínic is the first center with CAR-T in Europe that has received approval from a regulatory agency so that it can be used in patients with no other therapeutic options. The drug is of public origin, financed through crowdfunding and produced in a strictly academic environment, with no pharmaceutical companies behind it. The trials conducted at the Clínic with the collaboration of the Hospital Sant Joan de Déu have allowed the Aemps to trust in this therapeutic alternative: of the 58 patients who had a life expectancy of a few weeks, 38 were treated with CAR-T and 69% were still alive after one year. Forty-seven percent no longer had the disease after this period

The Ministry of Health has so far financed two CAR-T therapies produced by the pharmaceutical companies Novartis and Gilead, but this is the first public alternative that it will finance; a milestone in the State, since it is the first treatment with genetically modified cells that achieves this. "The authorisation has to allow both access to patients who have no other treatment alternatives, as well as continue to generate knowledge about the drug so that, eventually, a centralised marketing authorisation for the whole of Europe is achieved", celebrated the head of the Department of medicines for human use at Aemps, César Hernández

The director of the Clinical Institute of Hemato-Oncological Diseases, Álvaro Urbano-Ispizua, stresses that this drug offers a response to patients with very advanced acute lymphoblastic leukaemia and highlights that the trial shows that ARIO-0001 produces a complete response in 70% of these patients. The fact of producing it directly in the hospital, he adds, means it can be prepared "in a very short time" and repeat doses if necessary, a fundamental aspect taking into account the fragility of the patients.

More than 175 professionals from different disciplines have participated in the development of this treatment, which for now will only be used in the Hospital Clínic, according to the authorisation of the Aemps. However, the idea is that in the next few years at least nine hospitals throughout Spain - where a hundred new cases are diagnosed each year - will learn to use the drug and will also be able to administer it. "We are opening the clinical trial so that they can gain experience," Urbano-Ispizua explained.

The Clinic, therefore, wants to export this finding wherever possible. "The preparation method used to obtain our CAR-T is consistent and reproducible and allows lowering the cost of production of the therapy to make it affordable to academic institutions and make it available to all patients," says Manel Joan, head of the immunology service at Hospital Clínic.

The patient is his own donor

The Chimeric Antigen Receptor-T Receptor (CAR-T) is a very complex and personalised type of gene therapy that has very good results in fragile patients with acute lymphoblastic leukaemia, who account for between 10% and 15% of patients with this disease. In these people it is not possible to stop the proliferation of tumour cells with chemotherapy or bone marrow transplantation, and they end up resisting treatment. Many of them end up relapsing and dying. "When treatment options are exhausted, there is a need for less toxic and more targeted solutions in which immunotherapy can play a key role," Hospital Clinic sources explain.

With CAR-T immunotherapy, the patient becomes his or her own donor: the white blood cells responsible for the immune response (T lymphocytes) are extracted from the patient. Through a technique that allows the separation of the components of the blood (apheresis), a quantity of lymphocytes is obtained and these are genetically reprogrammed in the laboratory so that they can specifically recognise the tumour cells and attack them. They are then re-implanted.

The engineered cell gains anti-tumour capacity to act on its own and stop cancer proliferation. These individually modified lymphocytes are the cell product obtained (called ARIO-0001) and the drug that has received authorisation for use by the Aemps. Immunologists at Hospital Clínic claim that after three weeks the response can already be observed in the patient. "In our case, the CAR-T has been developed from our own antibody created in the hospital more than 30 years ago and to which we found a new application," explains immunologist Manel Joan.

"It is clear that the Catalan health system is at the forefront of advanced therapies and personalised medicine." said the director of Care at the Catalan Health Service (CatSalut), Xènia Acebes, who has highlighted the collaboration between institutions and public and private funding through donations to achieve this milestone. "We have the first CAR-T not produced by pharmaceutical companies and our obligation is to deploy it. Undoubtedly, this is a starting point so that other CARs can be produced here," said Acebes.

The therapy has been made possible thanks to the ARI Project, which raised nearly 1.8 million euros from companies, foundations, associations and individuals. "Today is a day of celebration but also a moment to highlight health research, which now more than ever, due to the pandemic, has demonstrated its importance," said the general director of the Clínic, Josep Maria Campistol, referring to the rapid development of vaccines against covid.

But the soul of the project was Ariana Benedé, who died on September 2, 2016 of acute lymphoblastic leukaemia, and who until the last moment fought to get the necessary funds to import a therapy that was then only used in the United States and China. The researchers have also had words of thanks for the young woman, whose great enthusiasm they have highlighted. "Today is a day of tribute to Ari. It would be a very special day for her, she deserved it," said Campistol.