After UK, US FDA approves 2 gene therapies to treat sickle-cell patients

The US Food and Drug Administration on Saturday approved two cell-based gene therapies -- Casgevy and Lyfgenia -- to sickle cell disease (SCD) patients 12 years and older.

This comes weeks after the UK approved the gene therapy, a world first, to treat blood disorders sickle-cell disease and thalassemia using the gene-editing tool CRISPR, which won its inventors the Nobel Prize in 2020.

Casgevy and Lyfgenia are made from the patients’ own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant.

Sickle cell disease is a group of inherited blood disorders affecting approximately 100,000 people in the US. The primary problem in sickle cell disease is a mutation in haemoglobin -- a protein found in red blood cells that delivers oxygen to the body’s tissues -- that causes red blood cells to develop a crescent or “sickle” shape.

These sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). The recurrence of these events or crises can lead to life-threatening disabilities and/or early death.

“Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today,” said Nicole Verdun, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, in a statement.

“Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” Verdun added.

Casgevy is the first FDA-approved therapy utilising CRISPR/Cas9 -- a type of genome editing technology that modifies patients’ blood stem cells.

CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut.

Lyfgenia uses a lentiviral vector (gene delivery vehicle) to genetically modify the patient’s blood stem cells to produce HbAT87Q. It is a gene-therapy derived haemoglobin that functions similarly to haemoglobin A, which is the normal adult haemoglobin produced in persons not affected by sickle cell disease.

Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient.

The FDA granted approval of Casgevy to Vertex Pharmaceuticals and approval of Lyfgenia to Bluebird Bio Inc.

The FDA said it will continue to monitor patients who received Casgevy or Lyfgenia in a long-term study to further evaluate each product’s safety and effectiveness.