‘Revolution’ drug for patients with beta-thalassemia

They are forced to undergo blood transfusions every 2-3 weeks throughout their life. And every day they have to take therapy to limit the accumulation of iron in vital organs such as the heart, liver and pancreas. In Italy there are about 7 thousand patients with beta-thalassemia, an inherited genetic disease caused by a defect in the production of hemoglobin, the ‘spacecraft’ protein that carries oxygen throughout the body. The good news is that “scientific research is revolutionizing therapy, because for the first time a new drug, luspatercept, has been shown to reduce the number of transfusions needed”, improving the quality of life of patients and limiting iron accumulation. and its consequences, “with a hope of improved survival”. This was underlined by experts who spoke at a virtual press conference promoted by Celgene, now part of Bristol Myers Squibb (Bms), on the eve of World Thalassemia Day. “In the world there are about 90 million carriers of the genetic mutation capable of determining one of the types of beta-thalassemia – explains Maria Domenica Cappellini, professor of internal medicine at the State University of Milan – In Italy there are about 3 million healthy carriers. If only one gene of the beta chains of hemoglobin changes, we speak of beta-thalassemia minor, which does not cause relevant symptoms and does not need therapy. If, on the other hand, both genes of the beta chains that form hemoglobin are mutated, we have the form of beta-thalassemia major, which presents a severe clinical picture, with severe anemia “. “Italy is one of the most affected countries in the world”, highlights the specialist, recalling that “the disease was present above all among the populations of malarious areas such as the islands, the southern regions and the Po Delta area, since malaria was a natural selection factor of the thalassemia defect. Currently the disease is widespread in the Mediterranean basin, in the Middle East, North Africa, India and South East Asia, areas still endemic for malaria “. If in the sixties of the last century patients with thalassemia major did not survive beyond 10-15 years, today thanks to the combination of transfusion and iron chelating therapies their life expectancy can exceed 50 years. “Sardinia is the second region, after Sicily, with the highest number of patients with transfusion-dependent beta-thalassemia, equal to about 900 people, and in the center of Cagliari we follow 460 – reports Raffaella Origa, medical director at the Microcitemico ‘A. Cao’ hospital in Cagliari and researcher in Pediatrics at the University of the Sardinian capital – These numbers require a dedicated organizational structure “, aimed at addressing” first of all the problem of blood shortage, once limited to the summer period, but in the last year aggravated by the pandemic from Covid-19. Sardinia imports about 27 thousand units of blood each year from other regions. In some periods, patients have to postpone the transfusion, or receive less blood than necessary. In addition, in Cagliari we have set up a multidisciplinary team that guarantees 360-degree assistance to both adult and pediatric patients “, and” we are involved in clinical trials at an international level “. Because” where research is done, patients are best followed, even in the administration of traditional therapies “.” The weight of the disease on the daily life of patients is really important – testifies Raffaele Vindigni, president of United Onlus (National Federation of Thalassemia, Sickle Cell Disease and Rare Anemias Associations) – It is estimated that these people spend more 30 days a year in the hospital for transfusions and follow-up examinations. It is time taken from family, study, work, free time and holidays. Their life, in fact, revolves around the transfusion center. Furthermore, in Italy, the disease is not treated uniformly throughout the territory. In fact, beta-thalassemia does not only require blood transfusions, but also very clear protocols with instrumental tests to be performed with precise frequency. Today there are centers that carry out these analyzes every 4 or 6 months, others every 2 years. It is a very serious situation “, Vindigni points out.” In 2017 – he recalls – with the Italian Society of Thalassemia and Hemoglobinopathies (Site), we presented to the Ministry of Health the proposal for the establishment of the Thalassemia Network, so that all centers are connected to a digital platform, where information can be exchanged to improve care and, above all, standardize it across the territory. The implementing ministerial decree has been signed and is now being examined by the State-Regions Conference. Furthermore, patients are very eagerly awaiting innovative therapies, capable of improving the quality of life and offering the opportunity to reduce the need for blood. We ask institutions to listen to the needs of patients, who cannot wait “.” Today, for the first time, an innovative molecule, luspatercept, is able to reduce the need for transfusions “, continues Cappellini. The therapy” consists of an injection. subcutaneous every 21 days and can potentially be administered to all patients affected by beta-thalassemia, unlike other options available such as bone marrow transplantation, the only therapy that can lead to recovery, but with the limit of the availability of a compatible donor, or gene therapy, yet to be consolidated “.” Luspatercept reduces ineffective erythropoiesis, allowing the production of mature red blood cells – continues the expert – This is demonstrated by the results of the phase III study Believe, published in the ‘New England Journal of Medicine ‘. 336 patients with transfusion-dependent thalassemia were enrolled in 65 centers in 15 countries. The primary objective of the study was to reduce the need for transfusions by at least 33% from baseline, i.e. to the units the patient was accustomed to transfuse in the six months prior to taking the drug. The result was achieved by 70% of patients. The second objective was to evaluate a reduction of more than 50% in transfusion requirements, observed in more than 40% of patients. Furthermore, the response has been maintained over time “.” With Celgene, for over 30 years, we have been focused on haematological diseases – declares Cosimo Paga, Executive Country Medical Director, Bms – The progress achieved has significantly improved survival and quality of life of patients. Luspatercept is the first and only erythroid maturation-promoting agent approved in Europe and represents a new therapeutic class. Our commitment to serious diseases such as beta-thalassemia is evidenced by the activation of compassionate programs “in which,” thanks to the free supply of drugs during the negotiation period with the Italian regulatory agency Aifa, we allow patients to access therapies earlier. marketing. To date, requests for activation of the compassionate use program have been received from 57 centers, with over 100 patients already included. “In Cagliari, the program began last February, with the enrollment of 13 patients:” We cannot draw conclusions yet – says Origa – but it is possible to confirm in a preliminary manner the results of the Believe pivotal study “.