Standard treatments include the use of oral hydroxyurea and chronic transfusion regimens. But there are also other options: allogeneic hematopoietic cell transplantation and gene engineering therapies
I have a 7 year old son with sickle cell anemia, not serious at the moment. What are the best therapies available? Could a new cure arrive that can cure him permanently?
He replies Emanuele Angelucci, Director of the Hematology and Cellular Therapies Unit at the IRCCS San Martino Polyclinic Hospital in Genoa; vice president of the Italian Society of Hematology
Sickle cell anemia or sickle cell anemia is one of the most common and widespread forms of hereditary diseases in the world., especially in Africa and South-East Asia. Following migratory flows, the mutated gene responsible for the disease spread to America, Europe, Australia and if in Italy the pathology affected almost only the southern regions, today it is present throughout the national territory. characterized by the presence, genetically determined, of a diseased hemoglobin (hemoglobin S or HbS) that causes a tendency of red blood cells to sickle (hence the name), that is, to deform the membrane with consequent phenomena of vascular obstruction. Anemia is only one of the possible consequences, but the clinical situation of patients is much more complex vascular occlusive phenomena (and consequent painful syndromes), multi-organ damage such as acute pulmonary syndromes, cerebrovascular events, renal failure, splenic infarctions and more.
Therapies in use
The severity of the individual patient’s situation is defined by the frequency and severity of these events. The quality and length of life are heavily compromised. The evolution over the years is often bizarre and the clinical events are in many cases unpredictable. Standard treatments (in Italy and according to international guidelines) currently involve the use of oral hydroxyurea (a mild chemotherapy that increases the amount of fetal hemoglobin) and chronic transfusion regimens which allow sickle cell red blood cells to be replaced with normal red blood cells (erythrocyte exchange) or to reduce the concentration of sickle cell red blood cells (simple transfusion). While the first strategy (hydroxyurea) is implemented in all forms of disease, transfusion therapy reserved for severe forms. The objective is to prevent or reduce the frequency and severity of sickle cell crisis episodes.
A few years ago it was registered by the EMA, the European Medicines Agency, a drug to reduce sickle cell crisescrizanlizumab (monoclonal antibody against P-selectin, a factor that plays a crucial role in triggering painful attacks), administered intravenously every 28 days, but the authorization was recently withdrawn by EMA itself due to lack of confirmation of effectiveness in real-life studies (still available in the US). Other drug similar in therapeutic purpose, but not in mechanism of action, voxelotor (anti-sickling mechanism, daily oral administration) available in the United States and Europe, in Italy currently prescribable in CNN class (i.e. the cost of which is borne entirely by the citizen or by the hospital where it decides to be able to bear the cost, until the conclusion of the negotiation process), over 12 years.
All these therapies act downstream, i.e reducing or preventing painful crises due to vaso-occlusive eventsbut not curing the pathology and are chronic therapies, which must therefore be taken for life. To be able to heal permanently the only options are allogeneic hematopoietic cell transplantationwhich has been developed for years and whose number has increased significantly recently, and gene engineering therapies that is, those that genetically modify the patient’s own hematopoietic stem cell and then reintroduce it into the body through an autologous transplant procedure. The first gene engineering technique is called gene insertion (gene insertion) and, as the name suggests, consists of inserting the normal hemoglobin gene into the stem cell. This procedure was approved by EMA, but was never introduced in Europe due to lack of economic agreement with the manufacturer.
In the United States (where there is no national health system and patients, who can afford insurance, pay for the treatment) available, but at a truly demanding price: around 2.5 million dollars for each product. A very high figure, certainly, but which must be considered in perspective because this therapy can definitively cure patients who would otherwise require equally expensive treatments overall (if not longer) for life. The American FDA confirmed the registration despite the reporting of two cases of acute myeloid leukemia in sickle cell subjects undergoing the procedure, as the leukemia was not considered a consequence of the product. At the last annual meeting of the American Society of Hematology (ASH), held in December in San Diego, they were then presented data from a gene therapy study called gene editingwhich consists in promoting the production of fetal hemoglobin through a mechanism for removing its blockage which occurs physiologically immediately after birth.
The patient thus becomes able to produce fetal hemoglobin, a good and efficient hemoglobin not associated with any of the problems of sickle cell syndrome. Over 40 patients treated in a study (conducted by Professor Franco Locatelli of the Bambino Ges Hospital in Rome) with complete resolution of symptoms in over 90% of cases. This product was recently approved in the UK (in November) and in the USA (December) and EMA approval is expected very soon. There is no price information yet on this product. Obviously all these techniques (transplant and gene therapies) are reserved for patients with severe forms of sickle cell syndrome. It is expected that gene therapy will, at least for the moment, be reserved for patients over the age of 12.
The reimbursement system
These therapies in genetic diseases have raised the problem of a therapy with a high (if not very high) price but with a benefit (value) that extends for many years (possibly for a lifetime)therefore generating, in addition to a significant clinical benefit, also the saving of other therapies and both direct and indirect costs that are likely to be equally high, if not higher, but spread over much longer times. The reimbursement system currently used in Italy (the entire cost is paid by the NHS to the manufacturing company at the time of treatment), whatever the outcome, it is no longer adequate to this evolution of medical techniques. It is essential to find reimbursement methods spread over time and based on the benefit obtained for the patient to make therapies truly accessible to patients.
Corriere della Sera also on Whatsapp. sufficient click here to subscribe to the channel and always be updated.
January 24, 2024 (modified January 24, 2024 | 08:21)
© ALL RIGHTS RESERVED