Code to cure: FDA approves two novel therapies for sickle cell treatment

Written by Felix Myhill (Assistant Editor)
Cell therapy FDA Gene editing Gene therapy News
FDA approves Casgevy and Lyfgenia

Two landmark treatments, LYFGENIA™ and CASGEVY™, have been approved by the US Food and Drug Administration (FDA) for the treatment of sickle cell disease in patients 12 years and over.

Approximately 100,000 people have sickle cell disease in the US and there is currently an unmet clinical need for a cure. The FDA has moved towards tackling the disorder, which disproportionately affects African Americans, by approving the use of two novel cell-based gene therapies: LYFGENIA and CASGEVY.

Sickle cell disease is a genetic disorder that is caused by misfolded hemoglobin protein in red blood cells, which gives rise to structurally abnormal, crescent-shaped cells. These cells cause blockages and lead to restricted blood flow and oxygen delivery to tissues, which results in painful vaso-occlusive events and organ damage. Recurrence of such events can lead to life-threatening disabilities and premature death.  

To address the unmet clinical need of sickle cell disease, the FDA recently approved the use of LYFGENIA and CASGEVY.  

Both are autologous therapies, meaning that the patient’s cells are extracted, modified and then reintroduced. They also both require the patient to undergo high-dose chemotherapy before treatment to remove bone marrow cells that the therapeutic stem cells replace. However, LYFGENIA and CASGEVY differ in the method by which blood stem cells (HSCs) are modified.  

LYFGENIA uses a lentiviral vector to introduce a functional β-globin gene to HSCs. These modified HSCs produce HbAT87Q, a hemoglobin that is functionally analogous to normal adult hemoglobin (HbA), which reduces the sickling of red blood cells and subsequently can limit vaso-occlusive events. 

CASGEVY is produced by modifying HSCs with CRISPR/Cas9, a gene-editing complex that can remove, add or replace DNA at specific loci. CASGEVY’s edited HSCs produce a high proportion of fetal hemoglobin (HbF) causing subsequent differentiated red blood cells to have a lower incidence of sickling.  

While the FDA has previously approved the use of lentiviral vectors for other advanced therapies, such as Betibeglogene autotemcel or Elivaldogene autotemcel, CASGEVY’s authorization marks the first FDA-approved therapy that leverages CRISPR/Cas9. This promptly follows the world’s first authorization of CASGEVY by the United Kingdom Medicines and Healthcare Products Regulatory Agency (London, UK) in November 2023.  

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.” 

Source

  1. US Food and Drug Administration. FDA approves first gene therapies to treat patients with sickle cell disease. [Accessed 18 December 2023]
  2. Bluebird Bio. Bluebird Bio announces FDA approval of LYFGENIA™ (lovotibeglogene autotemcel) for patients ages 12 and older with sickle cell disease and a history of vaso-occlusive events. [Accessed 18 December 2023]
  3. Vertex Pharmaceuticals. Vertex and CRISPR Therapeutics announce US FDA approval of CASGEVY™ (exagamglogene autotemcel) for the treatment of sickle cell disease. [Accessed 18 December 2023]
  4. Kingwell, K. Lentiviral vector gene therapies come of age with two FDA approvals. Nat. Rev. Drug Discov. 21(11), 790-791 (2022).