FDA approval for two new drugs
In November 2019, the US Food and Drug Administration (FDA) approved two new drugs for the treatment of sickle cell disease.
Crizanlizumab, a monoclonal antibody that targets the P-selectin adhesion molecule on endothelial cells and platelets, was approved to reduce the frequency of vaso-occlusive crises in adults and in children aged 16 years and older.
In a phase 2 study of patients with sickle cell disease (any genotype), crizanlizumab demonstrated a significantly lower rate of sickle cell-related pain crises, and a longer median time to first and second crises compared with placebo.
Voxelotor, which binds irreversibly to haemoglobin S to inhibit polymerisation, was granted accelerated approval for the treatment of sickle cell disease in adults and in children aged 12 years and older.
A randomised controlled study of a once daily dosing regimen in 274 participants with homozygous HbS or HbSB0 thalassaemia reported that a significantly higher percentage of participants on the 1500-mg dose of voxelotor had an increase in haemoglobin of 10.0 g/L (1.0 g/dL) compared with participants on placebo.
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Disease of red blood cells caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in sickle cell haemoglobin (HbS).
Sickle cells can obstruct blood flow and break down prematurely, and are associated with varying degrees of anaemia.
Obstruction of small blood capillaries can cause painful crises, damage to major organs, and increased vulnerability to severe infections.
Associated with lifelong morbidity and reduced life expectancy.
All infants are screened, with findings confirmed by haemoglobin electrophoresis, full blood count, reticulocyte count, and peripheral blood smear.
Treatment goals include symptom control (including pain management), and prevention and management of complications.
Sickle cell anaemia is caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in production of sickle cell haemoglobin (HbS). Other forms of sickle cell disease may occur if HbS is inherited from one parent and another abnormal haemoglobin, or beta thalassaemia, is inherited from the other parent (e.g., HbSC or HbSB thalassaemia). Sickle cell disease is associated with varying degrees of anaemia, red cell haemolysis, and obstruction of small blood capillaries causing painful crises, damage to major organs, and increased vulnerability to severe infections. Sickle cell trait occurs if HbS is inherited from one parent and the normal HbA from the other.
History and exam
Sickle Cell Center for Adults
Associate Professor of Medicine and Oncology
Johns Hopkins Medicine
SL has been the site principal investigator on several industry-funded studies with the following companies: Pfizer, Selexys, AstraZeneca, and Prolong. She also receives research funding from PCORI, HRSA, NIH, Global Blood Therapeutics, Ironwood, AstraZeneca, Prolong, and Selexys. SL is an author of one of the references in this topic.
Dr Sophie Lanzkron would like to gratefully acknowledge Dr Channing Paller, a previous contributor to this topic.
Instructor in Medicine
Division of Hematologic Neoplasia
Dana-Farber Cancer Institute
JB declares that he has no competing interests.
University College London Hospitals
AS declares that he has no competing interests.
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