FDA Approves Treatment for Sickle Cell Disease

Officials with the FDA have approved crizanlizumab-tmca (Adakveo, Novartis) to reduce the frequency of vaso-occlusive crises (VOCs) in patients aged 16 years and older with sickle cell disease, according to a press release.¹

Sickle cell disease, a genetic blood disorder, is associated with chronic inflammation, causing higher levels of cell adhesion proteins, including P-selectin, which make both the blood vessels and certain blood cells stickier and prone to multicellular interactions, or clusters, in the bloodstream.²

Previously known as SEG101, crizanlizumab-tmca represents the first FDA-approved medicine in sickle cell disease that binds to P-selectin, a cell adhesion protein that plays a central role in the multicellular interactions that can lead to vaso-occlusion.²

The approval is based on results from the 52-week phase 3 SUSTAIN trial, in which the primary efficacy outcome measure was the annual rate of VOCs leading to a health care visit. For the study, which included 198 patients with sickle cell disease, patients were randomized to receive either crizanlizumab-tmca 5 mg/kg, crizanlizumab-tmca 2.5 mg/kg, or placebo administered intravenously over 30 minutes on week 0, 2, and every 4 weeks thereafter.¹

According to the data, crizanlizumab-tmca 5 mg/kg significantly lowered the median annual rate of VOCs to 1.63 versus 2.98 compared with placebo (P=0.010), 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 hydroxurea use. Thirty-six percent of patients treated with crizanlizumab-tmca 5 mg/kg did not experience a VOC compared with 17% in the placebo arm. The median time to first VOC from randomization was 4.1 versus 1.4 months in the crizanlizumab-tmca 5 mg/kg and placebo arm, respectively.²

The most common adverse reactions 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, according to the FDA.¹

“We know this drug can decrease the frequency of sickle cell pain crises in a significant and clinically meaningful way,” principal investigator Kenneth Ataga, MD, director for Center for Sickle Cell Disease, University of Tennessee Health Science Center at Memphis, said in a statement.² “The approval of crizanlizumab is an important advancement for people living with this very difficult condition.”

Reference

• New Novartis medicine Adakveo (crizanlizumab) approved by FDA to reduce frequency of pain crises in individuals living with sickle cell disease [news release]. Novartis’ website. https://www.novartis.com/news/media-releases/new-novartis-medicine-adakveo-crizanlizumab-approved-fda-reduce-frequency-pain-crises-individuals-living-sickle-cell-disease. Accessed November 15, 2019.
• FDA approves crizanlizumab-tmca for sickle cell disease [news release]. FDA’s website. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizanlizumab-tmca-sickle-cell-disease. Accessed November 15, 2019.