Last reviewed: February 2020
Last updated: March  2020
20 Mar 2020

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.[24]

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.[25]

See Management: approach

See Management: treatment algorithm

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Summary

Definition

History and exam

Key diagnostic factors

  • parent(s) diagnosed with sickle cell anaemia, other sickle cell disease, or sickle cell trait
  • persistent pain in skeleton, chest, and/or abdomen
  • dactylitis

Other diagnostic factors

  • high temperature
  • pneumonia-like syndrome
  • bone pain
  • visual floaters
  • tachypnoea
  • failure to thrive
  • pallor
  • jaundice
  • tachycardia
  • lethargy
  • maxillary hypertrophy with overbite
  • protuberant abdomen, often with umbilical hernia
  • cardiac systolic flow murmur
  • shock

Diagnostic investigations

1st investigations to order

  • DNA-based assays
  • haemoglobin isoelectric focusing (Hb IEF)
  • cellulose acetate electrophoresis
  • high-performance liquid chromatography (HPLC)
  • haemoglobin solubility testing
  • peripheral blood smear
  • FBC and reticulocyte count
  • iron studies
More 1st investigations to order

Investigations to consider

  • pulse oximetry
  • plain x-rays of long bones
  • bacterial cultures
  • chest x-ray
More investigations to consider

Treatment algorithm

Contributors

Director

Sickle Cell Center for Adults

Associate Professor of Medicine and Oncology

Johns Hopkins Medicine

Baltimore

MD

Disclosures

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.

Peer reviewersVIEW ALL

Instructor in Medicine

Division of Hematologic Neoplasia

Dana-Farber Cancer Institute

Boston

MA

Disclosures

JB declares that he has no competing interests.

Consultant Haematologist

University College London Hospitals

London

UK

Disclosures

AS declares that he has no competing interests.

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