ARI-0001 [systematically named Varnimcabtagene autoleucel (var-cel), a second generation anti-CD19 chimeric antigen receptor (CAR) T-cell] granted local use authorization (under the rule of “hospital exemption”, HE) by the AEMPS (Spanish drug agency = Agencia Española de Medicinamentos y Productos Sanitarios) and just a little more than half-year ago (December 2021) PRIME (Priority Medicine) designation by the EMA (European Mediciness Agency) for patients >25 years old with relapsed or refractory (R/R) B cell acute lymphoblastic leukaemia (B-ALL). The authorization is based on the results of a phase 1 clinical trial (NCT03144583), but additional patients (already reimbursed by Spanish Health System), new clinical trials or compassionate uses with ARI-0001, have been produced and infused in our Hospital Clínic de Barcelona or our pediatric partner, Hospital Sant Joan de Déu. Although HE for adult ALL patients and compassionate uses (next to indicated commercial products that authorized our center) allow us to use CART19 therapy for treating our patients (our real aim of this development), the good clinical results, and petitions of different centers all around the world (specially from places where commercial products are not available) encouraged us to consider how we should proceed to extend our product to other patients.
Our Academic proposal is the result of the work of a multidisciplinary team, a point-of-care (PoC) procedure based on a well stablish protocol in a commercially available bioreactor and our home-developed lentivirus.
All the elements of our proposal follow the GMP standards, strictly controlled by the AEMPS and the regulations for Advanced Therapy Medicinal Products (ATMPs) of the EMA; although the product could be developed in our clean-rooms at Barcelona, our aim is to share procedures to allow production as a real PoC product, looking for partners that can reproduce all steps next to the patient. This multi-site cell production has been already accomplished with success in several clinical trials, while for a homogeneous lentiviral production, we decided (by now) to use facilities centralized in our university hospital. We expect to obtain first local authorization for this multicenter production in Spain, and later by EMA and other regulators (India). In fact, this experience is also supported by developing a clinical trial with 60 multiple myeloma patients under the treatment of a new own CART-BCMA (ARI-0002h).
We are convinced that it is a possible model, although most of the huge number of rules are mainly thought for pharma-companies and are not easily implemented by Academic entities. But if we want to have the best treatments for our patients, to find solutions with real options for Academic ATMPs developments is the only way to arrive where the commercial companies, the health systems and in general countries will not be able to arrive for different reasons (difficult recover of investments by complex reimbursement, low level of patients, no-sustainable expenses and procedures for economic and ecologic reason, ...).
