General Information

Adakveo (crizanlizumab-tmca) is a selectin blocker.

Adakveo is specifically indicated to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients aged 16years and older with sickle cell disease.

Adakveo is supplied as a solution for intravenous infusion. Administer Adakveo 5 mg/kg by intravenous infusion over a period of 30 minutes at Week 0, Week 2, and every 4 weeks thereafter. If a dose is missed, administer Adakveo as soon as possible. If Adakveo is administered within 2 weeks after the missed dose, continue dosing according to the patient's original schedule. If Adakveo is administered more than 2 weeks after the missed dose, continue dosing every 4 weeks thereafter. Adakveo maybe given with or without hydroxyurea.

Clinical Results

FDA Approval

FDA approval was based on SUSTAIN, a randomized, multicenter, placebo-controlled, double-blind study. A total of 198 patients with any genotype of sickle cell disease (HbSS, HbSC, HbS/beta0-thalassemia, HbS/beta+-thalassemia, and others) and a history of 2-10 VOCs in the previous 12 months were eligible for inclusion. Patients were randomized 1:1:1 to Adakveo 5 mg/kg (N = 67), Adakveo 2.5 mg/kg (N = 66), or placebo (N = 65) administered over a period of 30 minutes by intravenous infusion on Week 0, Week 2, and every 4 weeks thereafter, for a treatment duration of 52 weeks. The primary efficacy outcome was the annual rate of VOCs leading to a healthcare visit. A VOC leading to a healthcare visit was defined as an acute episode of pain with no cause other than a vaso-occlusive event that required a medical facility visit and treatment with oral or parenteral opioids, or parenteral NSAIDs.

Adakveo significantly lowered the median annual rate of VOCs to 1.63 vs 2.98 compared to placebo, which is equivalent to a 45% reduction. Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or hydroxyurea use. Additional results from the SUSTAIN study include: 

• A decrease in the median annual rate of days hospitalized to 4 vs 6.87 days when compared with placebo (a 42% reduction) 
• Thirty-six percent of patients treated with Adakveo did not experience a VOC, compared to 17% of placebo-treated patients
• The median time to first VOC was 4.1 for Adakveo vs 1.4 months for placebo

Side Effects

For additional information regarding Adakveo or vaso-occlusive crises in sickle cell disease, please visit the Adakveo web page.

Mechanism of Action

Adakveo (crizanlizumab-tmca) is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1. Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.