The FDA has granted SEG101 (crizanlizumab, Novartis) breakthrough therapy designation for the prevention of vaso-occlusive crises (VOCs) in sickle cell disease (SCD) among patients with all genotypes.
VOCs can lead to acute and chronic complications in patients, often requiring medical attention. They occur when blood cells stick to each other and to blood vessels but can be treated with therapies that reduce the stickiness.
SEG101 is an investigational, humanized anti-P-selectin monoclonal antibody that binds to P-selectin on platelets and endothelium in blood vessels. The agent blocks interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes, and averts their binding to P-selectin.
Positive data from the Phase 2 multicenter, open-label study CSEG101A2202, comparing SEG101 with placebo in patients with SCD, led to the breakthrough therapy designation.
SEG101 reduced the median annual rate of VOCs leading to health care visits by 45.3% compared with placebo (1.63 vs. 2.98; P = 0.01). Researchers noted the decrease whether or not patients received hydroxyurea therapy. In addition, the product significantly increased the number of patients who did not experience any pain crises compared to placebo (35.8% vs. 16.9%; P = 0.01).
There was a comparable incidence of treatment-emergent adverse events (AEs) and serious AEs in both SEG101 and placebo groups. AEs including arthralgia, diarrhea, pruritus, vomiting, and chest pain occurred at least twice as often in those taking SEG101 compared with placebo.