Novartis announced on January 8 that the monoclonal antibody candidate crizanlizumab (SEG101) has recently received FDA breakthrough therapy qualification for the prevention of vaso-occlusive crises (VOCs) in patients with all sickle cell disease (SCD) genotypes.
Sickle cell disease is an inherited disorder of hemoglobin molecule function. When hemoglobin molecules are exposed to various environments, red blood cell hemoglobin polymerizes and distorts to form sickles.P-selectin drives the process of vascular occlusion, a painful complication of sickle cell disease that generally occurs when the vascular circulation is blocked by sickle red blood cells.One of the most severe forms of the disease is acute chest syndrome, which is limited when blood flows to the lungs.
Crizanlizumab is a humanized monoclonal antibody that binds to P-selectin, a protein found on the surface of endothelial cells and platelets, and is expressed on platelet endothelial cells, causing mainly cell-cell interactions and involved in thrombosis- or sickle cell disease-related pain crises.
The FDA accreditation for crizanlizumab breakthrough therapy was based on data from a double-blind, randomized, placebo-controlled phase II trial.198 subjects were randomized to receive low-dose crizanlizumab (2.5 mg/kg, n = 66), high-dose crizanlizumab (5 mg/kg, = 67), or placebo (n = 65) intravenously for 14 doses for 52 weeks.Studies have shown that crizanlizumab significantly reduces the incidence of sickle cell disease-related pain crises and has a lower incidence of adverse events in patients with sickle cell disease.
Specific results showed that the median number of crisis cases per year in the high-dose crizanlizumab group was 1.63, placebo group 2.98 (low incidence of crisis in the high-dose crizanlizumab group 45.3%, P = 0.01).The median time interval between the first and second crisis was significantly longer in the high-dose crizanlizumab group than in the placebo group (4.07 vs 1.38 months, P = 0.001), the median time to second crisis was also significantly longer (10.32 vs 5.09 months, P = 0.02).Median annual incidence of uncomplicated crisis in the high-dose crizanlizumab group 1.08 cases, compared with 2 in the placebo group.91 cases (low incidence of uncomplicated crisis in high-dose crizanlizumab group 62.9%, P = 0.02).Adverse events occurred in more than 10% of patients in both treatment groups, but the incidence of adverse events was higher in the placebo group, which was more than twice that of the crizanlizumab group and mainly included arthralgia, diarrhea, pruritus, vomiting, and chest pain.
Novartis acquired ownership of crizanlizumab through the acquisition of Selexys Pharmaceuticals in 2012.