The FDA today approved Novartis’ crizanlizumab, previously known as SEG101, indicated for the reduction in frequency of vaso-occlusive crises (VOCs) in adult and pediatric patients at least 16 years of age and older.
Crizanlizumab is currently the first and only approved biologic that works by binding to P-selectin, a cell adhesion protein that involved in multicellular interactions and can lead to vaso-occulsion in sickle cell disease, according to Novartis’ official statement. Novartis says that by binding to p-selectin on the surface of an activated endothelium and platelets, crizanlizumab blocks interactions between endothelial cells, platelets, RBCs, and leukocytes.
“The approval of Adakveo marks a new era in the treatment of sickle cell disease, a genetic condition that places an extraordinary burden of unpredictable pain crises on patients and their families,” said Susanne Schaffert, PhD, president, Novartis Oncology says in a statement. “The stories we have heard from patients about their sickle cell pain crises are devastating. We are pleased to help reimagine medicine together with the sickle cell community and offer new hope for fewer VOCs.”
Today’s approval is based upon the results of a SUSTAIN, a randomized, multicenter, placebo-controlled, double-blind study that included 196 patients with any genotype of sickle cell disease and a history of 2-10 VOCs in the previous 12 months.
The primary efficacy outcome for SUSTAIN, according to the release, was the annual rate of VOCs leading to a healthcare visit (i.e,. an acute episode of pain with no cause other than a vaso-occulsive event that required a medical facility visit and treatment with oral or parenteral opioids, or parenteral NSAIDs; acute chest syndrome; hepatic sequestration; splenic sequestration; and priapism requiring a visit to a medical facility).
Overall, the annual rate of VOCs in the crizanlizumab arm (1.63) experienced a 45% reduction compared to the placebo arm (2.98). Reductions in the crizanlizumab arm were observed regardless of sickle cell genotype and/or hydroxyurea use.
Secondary and other efficacy outcomes included the annual rate of days hospitalized (crizanlizumab: 4 days; placebo: 6.87 days), the time to first VOC leading to a healthcare visit, and the number of patients that did not experience a VOC.
Warnings and precautions issued with crizanlizumab include infusion-related reactions and interference with automated platelet counts (i.e., platelet clumping).
Adverse reactions reported with the use of crizanlizumab include nausea, arthralgia, back pain, and pyrexia.
Novartis says that crizanlizumab should be available within the coming weeks.