The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease

摘要

Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2–10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.