Crizanlizumab-tmca Becomes First Approved Targeted Therapy for Sickle Cell Disease

The FDA approved crizanlizumab-tmca to reduce the frequency of vaso-occlusive crisis in patients aged 16 and older with sickle cell disease (SCD). The agent is a monoclonal antibody targeted against the P-selectin glycoprotein that is expressed on activated endothelial cells and platelets.

“[Crizanlizumab-tcma] is the first targeted therapy approved for SCD, specifically inhibiting selectin, a substance that contributes to cells sticking together and leads to vaso-occlusive crisis,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the agency’s Center
for Drug Evaluation and Research. “Vaso-occlusive crisis can be extremely painful and is a frequent reason for emergency department visits and hospitalization for patients with SCD.”

The approval was based on results from a randomized clinical trial of 198 patients with SCD and a history of vaso-occlusive crisis. Participants received either placebo or crizanlizumab-tmca at one of two doses (2.5 mg/kg or 5.0 mg/kg). Those receiving the higher crizanlizumab-tmca dose experienced an average of 1.63 pain episodes per year and 35% had no episodes. Patients in the placebo group averaged 2.98 annual pain episodes and 17% had no episodes. Treatment with crizanlizumab-tmca also delayed the time to first vaso-occlusive crisis after the start of treatment, from 1.4 months to 4.1 months.

AEs associated with crizanlizumab-tmca included back pain, fever, arthralgia, and nausea. The FDA advises health care professionals to monitor patients for infusion-related reactions and discontinue the drug for severe reactions. Patients should also be monitored for interference with automated platelet counts or platelet clumping.

Sources: FDA press release, November 15, 2019.