AIFA green light for the reimbursement of Adakveo® (chrysanthemum)
Novartis announced that the Italian Medicines Agency (AIFA) approved the reimbursement Adakveo® (crizanlizumab) for the prevention of vaso-occlusive crises (vaso occlusive crises – VOC) recurrent in patients with sickle cell disease from age equal to and over sixteen who have submitted at least two VOCs in the previous twelve months. Crizanlizumab – to which AIFA has recognized the requirement of conditional innovation – can be administered as an add-on therapy to hydroxyurea / hydroxycarbamide (HU / HC) or as monotherapy in patients for whom HU / HC is inappropriate or inadequate, where for inappropriate / inadequate we mean insufficient efficacy or the presence of tolerability problems, insufficient compliance.
Sickle cell anemia, which in Europe it affects about 50,000 people in Italy is considered a rare haematological pathology due to the difficulty of tracing and diagnosis: those registered with a serious clinical picture are about 2,500-2,800, although according to experts there is an important undercurrent equal to about double the number of patients. Crizanlizumab, designated orphan drug, binds to P-selectin, a cell adhesion protein that plays a central role in multicellular interactions that can result in vaso-occlusion.
Vaso-occlusive crises (VOC) are serious, unpredictable events and can represent real health emergencies due to their rapid evolution and high mortality. As evidenced by the international SWAY (Sickle Cell World Assessment Survey) research, 91% of patients report at least one vaso-occlusive crisis in the 12 months prior to the survey. Overall, patients reported an average of 5.3 VOCs in the previous 12 months, most of which managed with medical intervention.
“The approval of the reimbursement in Italy of the first targeted therapy for recurrent vaso-occlusive crises represents very important news both for the patient community and for clinicians – commented Lucia De Franceschi, Associate Professor of Internal Medicine, AOUI Verona and University of Verona – Crizanlizumab, thanks to its peculiar mechanism, acts directly on chronic inflammatory vascular disease, which is the basis of the numerous clinical complications of patients with sickle cell syndrome. Furthermore, crizanlizumab has a profile of uniqueness that makes it very interesting for us doctors because it could help us manage even those patients who have failed or do not accept therapies considered standard “.
The SCAN (Sickle Cell Anemia Narrations) project
Give one narrative medicine project by ISTUD Foundation, promoted by Novartis, it also clearly emerged that sickle cell anemia has a significant impact on the quality of life of patients, from the emotional to the professional or scholastic sphere: in the periods in which symptoms occur, in fact, people with anemia sickle cell find it difficult to concentrate and carry out their study or work activities. On average are absent 39 days from their workplace or school. Other activities of daily life, such as shopping for example, are also often affected by the disease. Add to this that more than 50% of people with sickle cell anemia have transfusions at least once a month. However, despite these difficulties, the narratives also show the great desire of these people to cope with the care and the right assistance.
Compared to the diagnosis, in 43% of cases it is carried out and communicated by a center other than the one in which one is currently being treated, often represented by a pediatric center. However, there are those who arrived at the diagnosis after one pilgrimage between several care centers (28%). In a few cases, the diagnosis was made following a traumatic event during childbirth, or in the same center where one is still being treated. Furthermore, in a third of the cases reported (33%) it is specified that initially a diagnosis other than that of sickle cell anemia was made, confused with other forms of anemia – in particular Beta Thalassemia – or other conditions such as growth pains and rheumatism.
“We are really proud from being able to make the first targeted therapy for recurrent vaso-occlusive crises in sickle cell anemia available to patients and the medical profession – he says Luigi Boano, General Manager Novartis Oncology Italy – This result testifies how our continuous commitment to the research and development of innovative solutions is able to bring about an important change in the management of patients with this pathology, which is currently an orphan of therapeutic solutions “.
The approval of reimbursement by AIFA follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and the same approval by the EMA, issued in October 2020 based on the results of the SUSTAIN clinical study, which showed that crizanlizumab significantly reduced the median annual rate of VOC by 45% (1.63, compared with 2.98 for placebo (P= .010)). Reductions in VOC frequency have been observed among patients regardless of sickle cell anemia genotype and / or use of hydroxyurea / hydroxycarbamide (HU / HC). There was a more than double increase in the percentage of patients without VOC who completed the study, compared to placebo. In the same study, crizanlizumab was shown to reduce the median annual rate of hospitalization days by 42% (4.0 days for crizanlizumab vs 6.87 days for placebo). On the basis of clinical studies, crizalizumab also has a favorable safety profile: in fact, similar adverse events were found between patients treated with the therapy and the placebo group.
Information about crizanlizumab
Crizanlizumab – formerly known as SEG101 – is indicated for the prevention of recurrent VOCs in patients with sickle cell disease from 16 years of age. It can be given as add-on therapy to HU / HC, or as monotherapy in patients for whom HU / HC is inappropriate or inadequate. It is the first and only targeted biologic drug that works by binding to P-selectin, a cell adhesion protein that plays a central role in multicellular interactions that cause vaso-occlusion in sickle cell anemia. By binding to P-selectin on the surface of the endothelium and activated platelets, crizanlizumab blocks the interactions between endothelial cells, platelets, red blood cells and leukocytes by preventing vasocclusion.
Crizanlizumab is now approved in 36 countries around the world, including the United States and EU Member States.
Sickle cell anemia
Sickle cell anemia is one of the most common genetic blood disorders in the world. It is a chronic, permanent and debilitating disease, of variable clinical severity. Sickle cell anemia is characterized by the alteration of the shape and physical properties of red blood cells and by a greater adhesiveness of the different blood cells than usual. In certain situations, these cells are activated and adhere to each other and to the inner wall of the blood vessels, forming agglomerates (cluster)[11]that they can slow, block and reduce the flow of blood and oxygen, causing damage to blood vessels and organs. This consequently leads to recurrent and unpredictable acute crises of painful vascular occlusion, also called vaso-occlusive crises responsible for organ damage. The painful crises typical of sickle cell anemia lead to acute and long-term complications, disrupting the lives of patients physically, socially and emotionally.
People with sickle cell anemia have inherited two abnormal copies of the hemoglobin gene from their parents. Those with “sickle cell trait” (also called “carriers”) have inherited an abnormal gene and a normal gene. Sickle cell trait can be asymptomatic, but individuals with the disease can pass it on to their children.If both parents have the trait, their children are 25% likely to have sickle cell disease, 50% to have sickle cell trait and 25% have two normal genes or have no sickle cell trait or sickle cell anemia. A simple blood test can determine if a person is a carrier of the sickle cell trait.