FDA approves crizanlizumab-tmca for sickle cell disease

On November 15, 2019, Food and Drug Administration approved crizanlizumab-tmca (ADAKVEO, Novartis) to reduce the frequency of vaso-occlusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease.

Efficacy was evaluated in 198 patients with sickle cell disease in SUSTAIN (NCT01895361), a 52-week, randomized, multicenter, placebo-controlled, double-blind trial. Patients were randomized (1:1:1) to crizanlizumab-tmca 5 mg/kg (N = 67), crizanlizumab-tmca 2.5 mg/kg (N = 66), or placebo (N = 65) administered intravenously over 30 minutes on week 0, 2, and every 4 weeks thereafter. Randomization was stratified by prior hydroxyurea (Y/N) and by the number of VOCs in the prior 12 months.

The primary efficacy outcome measure was the annual rate of VOCs leading to a healthcare visit, defined as an acute episode of pain with no cause other than a vaso-occlusive event requiring a medical facility visit and oral or parenteral opioids, or parenteral NSAIDs. Patients receiving crizanlizumab-tmca, 5 mg/kg, had a lower median annual rate of VOC compared to those receiving placebo (1.63 vs. 2.98, p=0.010). Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or hydroxyurea use. Thirty-six percent of patients treated with crizanlizumab-tmca 5 mg/kg did not experience a VOC compared to 17% in the placebo arm. The median time to first VOC from randomization was 4.1 vs. 1.4 months in the crizanlizumab-tmca 5mg/kg and placebo arm, respectively.

The most common adverse reactions (>10%) in patients receiving crizanlizumab-tmca were nausea, arthralgia, back pain, and pyrexia.

The recommended dose is 5 mg/kg intravenously over a period of 30 minutes on week 0, 2, and every 4 weeks thereafter.

View full prescribing information for ADAKVEO.

FDA granted this application priority review and orphan product and Breakthrough Therapy designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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