The Food and Drug Administration has approved Adakveo (crizanlizumab-tmca; Novartis) to reduce the frequency of vaso-occlusive crisis (VOC) in patients aged ≥16 years with sickle cell disease.
Crizanlizumab-tmca is a humanized IgG2 kappa monoclonal antibody that blocks the interactions between endothelial cells, platelets, red blood cells, and leukocytes by binding to P-selectin on the surface of the activated endothelium and platelets. “Adakveo is the first targeted therapy approved for sickle cell disease, 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 FDA’s Center for Drug Evaluation and Research.
The approval of Adakveo was based on data from the multicenter, double-blind, placebo-controlled phase 3 SUSTAIN study that evaluated its efficacy in 198 patients with sickle cell disease. Patients were randomized 1:1:1 to Adakveo 5mg/kg, 2.5mg/kg, or placebo administered by intravenous (IV) infusion over 30 minutes on Week 0, Week 2, and every 4 weeks thereafter for a total of 52 weeks. The primary end point 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 that required a medical facility visit and treatment with oral or parenteral opioids, or parenteral NSAIDs).
Results showed that Adakveo significantly reduced the median annual rate of VOCs by approximately 45% vs placebo (1.63 vs 2.98, respectively; P =.010). Reductions in VOC frequency were observed regardless of sickle cell disease genotype and/or hydroxyurea use.
Additionally, patients treated with Adakveo achieved key secondary end points, which included a 42% reduction in the median annual rate of days hospitalized vs placebo (4 vs 6.87, respectively); median time to first VOC was 4.1 months with Adakveo vs 1.4 months with placebo. Moreover, 36% of Adakveo-treated patients did not experience a VOC compared with 17% of placebo-treated patients.
Regarding safety, the most common adverse reactions were nausea (18%), arthralgia (18%), back pain (15%), and pyrexia (11%).
The FDA previously granted Priority Review and Breakthrough Therapy designations to Adakveo. The product is expected to be available in the coming weeks in 100mg/10mL single-dose vials.
The Company is also offering a patient support program called Adakveo Support at PANO (Patient Assistance Now Oncology) to help eligible patients start and stay on treatment.
For more information visit novartis.com.