Adnkronos Rome, October 9 (Adnkronos Salute) – "This is a truly important step towards making a treatment with numerous advantages available to Italian patients with hemoglobinopathies, including thalassemia and sickle cell disease." This is how Franco Locatelli, Professor of Pediatrics at the Catholic University of the Sacred Heart in Rome and Director of the Department of Pediatric Hematology and Oncology at the Bambino Gesù Children's Hospital, commented on the news of the publication in the Official Journal by the Italian Medicines Agency (AIFA) of the reimbursement of exagamglogene autotemcel (exa-cel), the first and only gene editing therapy approved in Europe for the treatment of patients with transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).
"The first advantage," explains Locatelli, principal investigator of the Climb-111 and Climb-121 studies that led to the treatment's approval by regulatory agencies, is precisely the possibility of being "accessible to anyone" who meets the criteria for reimbursement by AIFA. This is very different from a bone marrow transplant, where a compatible donor must be identified. The second significant aspect, the expert continues, is that the safety profile of a therapy based on edited cells to reactivate fetal hemoglobin synthesis is significantly superior to that of an allogeneic transplant, and therefore it can also be considered for those adolescent and young adult patients for whom an allogeneic stem cell transplant is too risky.
Another strength concerns efficacy. "The data from clinical trials are particularly encouraging and exciting," he emphasizes. "Suffice it to say that, in the study for its use in thalassemia, which I coordinated internationally, all patients who received the infusion of the edited cells, at the last analysis, achieved transfusion independence. Three required more time than the remaining 53, but a total of 56 out of 56 stopped receiving transfusions, with average hemoglobin levels around 12 grams per deciliter. Of course," he observes, "the levels are not only sufficient to make them transfusion-independent, but also good enough to guarantee an excellent quality of life."
In this regard, "two studies have just been published in the journal Blood Advances," Locatelli explains, "which document a clear benefit for both thalassemia and sickle cell disease, in adolescents and adults." Specifically, "for sickle cell disease patients, the risk of hospitalization for severe, painful vaso-occlusive crises is reduced; for thalassemia patients, school attendance is increased in adolescents, physical and work performance is improved, and fatigue is reduced," a feeling of profound, highly debilitating tiredness typical of the disease. This is "an extraordinary result."
The treatment is currently indicated and reimbursed for patients aged 12 to 35. "These limitations arise from the evidence from clinical trials, that is, from the criteria developed during the trials," the expert specifies. However, "a study is underway to expand its use to pediatric patients. Here too, Bambino Gesù is the only Italian institution participating," he adds. "The data will be presented at the next meeting of the American Society of Hematology in early December, and without wanting to give any further details out of respect for the embargo, I can say that the data are very encouraging." Moreover, he reflects, "the genome editing trend is important and will certainly lead—I am certain—to the cure of other hereditary diseases. But genome editing," Locatelli states, "could also play a significant role in anti-cancer therapy approaches, with the editing of CARTD cells to make them more efficient and longer-lasting. It's a momentous turning point," he remarks, "truly a revolution that meets patients' needs."