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Last reviewed: 20 Apr 2025
Last updated: 18 Feb 2025
18 Feb 2025

Gene-editing therapy, exagamglogene autotemcel, available through managed access agreement in National Health Service (NHS) England

Exagamglogene autotemcel, a gene-editing therapy, has been approved by the National Institute for Health and Care Excellence (NICE) for use in the NHS in England for patients with severe sickle cell anaemia.

Patients aged 12 years and older with βS/βS, βS/β+ or βS/β0 genotype will be eligible for exagamglogene autotemcel, if they:

  • have recurrent vaso-occlusive crises (at least 2 during the previous 2 years), and

  • are suitable for haematopoietic stem cell transplant, but a human leukocyte antigen-matched donor is not available.

Exagamglogene autotemcel is a one-time gene therapy that uses CRISPR gene editing technology to alter the patient's own haematopoietic stem cells to produce higher levels of fetal haemoglobin in red blood cells.

The decision to approve exagamglogene autotemcel is based on clinical data from a multiphase, single-arm, open-label trial. In phase 3 of the trial, 29 of 30 patients (97%) who received exagamglogene autotemcel (and had sufficient follow-up to be evaluated) were free from vaso-occlusive crises for at least 12 consecutive months (mean duration of freedom from vaso-occlusive crises: 22.4 months).[101]

Final draft guidance and the managed access agreement are available from the UK NICE.[102]

The managed access agreement is a time-limited agreement that sets out the conditions under which people will be able to have NHS-funded treatment.[103]

Further data will be collected to address the uncertainties in the clinical or cost-effectiveness data.

See Management: emerging

Original source of update

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
Full details

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
Full details

Risk factors

  • genetic
Full details

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
Full details

Investigations to consider

  • pulse oximetry
  • plain x-rays of long bones
  • bacterial cultures
  • chest x-ray
Full details

Treatment algorithm

ACUTE

vaso-occlusive crisis

acute chest syndrome

ONGOING

chronic disease

Contributors

Authors

Sophie Lanzkron, MD, MHS

Director

Sickle Cell Center for Adults

Associate Professor of Medicine and Oncology

Johns Hopkins Medicine

Baltimore

MD

Disclosures

SL declares consultancy (Bluebird bio, Novo Nordisk, Pfizer, Novartis, Magenta); honoraria (Novartis); research funding (Imara, Novartis, GBT, Takeda, CSL-Behring, HRSA, PCORI, MD CHRC); stocks (Pfizer, Teva). SL is on the executive board of the National Alliance for Sickle Cell Centers (uncompensated).

Acknowledgements

Dr Sophie Lanzkron would like to gratefully acknowledge Dr Channing Paller, a previous contributor to this topic.

Disclosures

CP declares that she has no competing interests.

Peer reviewers

James Bradner, MD

Instructor in Medicine

Division of Hematologic Neoplasia

Dana-Farber Cancer Institute

Boston

MA

Disclosures

JB declares that he has no competing interests.

Adrian Stephens, MB BS, MD, FRCPath

Consultant Haematologist

University College London Hospitals

London

UK

Disclosures

AS declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Bain BJ, Daniel Y, Henthorn J, et al. Significant haemoglobinopathies: a guideline for screening and diagnosis: a British Society for Haematology guideline. Br J Haematol. 2023 Jun;201(6):1047-65.Full text  Abstract

DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020 Apr 28;4(8):1554-88.Full text  Abstract

National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease: expert panel report, 2014. Sep 2014 [internet publication].Full text

Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020 Jan 28;4(2):327-55.Full text  Abstract

Trompeter S, Massey E, Robinson S, et al. Position paper on International Collaboration for Transfusion Medicine (ICTM) Guideline 'Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline'. Br J Haematol. 2020 May;189(3):424-27.Full text  Abstract

Wethers DL. Sickle cell disease in childhood: part I. Laboratory diagnosis, pathophysiology and health maintenance. Am Fam Physician. 2000 Sep 1;62(5):1013-20, 1027-8.Full text  Abstract

Reference articles

A full list of sources referenced in this topic is available here.

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