US FDA approves two therapies that can ‘edit gene of sickle cell patients’

The United States Food and Drug Administration (FDA) has approved two gene-based treatments for sickle cell disease.

The US FDA, in an announcement published on Friday, said the “milestone” treatments are Casgevy and Lyfgenia.

Sickle cell disease is an inherited red blood cell disorder in which the body produces abnormal haemoglobin that causes the red blood cells to become sticky and hard, according to the US Centers for Disease Control and Prevention (CDC).

Casgevy was approved for people who are 12 years and older with recurrent vaso-occlusive crises.

According to the FDA, Casgevy utilises a type of novel genome editing technology — CRISPR/Cas9 — that can accurately edit DNA.

“Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology,” the FDA said.

“Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.

“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.

“The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery.

“In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.”

LYFGENIA

Lyfgenia was approved for people who are 12 years and older with sickle cell disease and a history of vaso-occlusive events.

According to FDA, Lyfgenia is a
cell-based gene therapy that uses a lentiviral vector for genetic modification.

“With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease,” the agency said.

“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 PROCEDURE

According to FDA, Casgevy and Lyfgenia are made from the patient’s own blood stem cells, which are modified and given back as a one-time, single-dose infusion as part of a
hematopoietic stem cell transplant.

“Prior to treatment, a patient’s own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia,” the agency said.

“Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness.”

‘IMPORTANT MEDICAL ADVANCE’

Speaking on the approvals, Peter Marks, the director of FDA’s Center for Biologics Evaluation and Research, said the treatments represent an “important medical advance” in the deployment of innovative cell-based gene therapies.

Marks said the approvals follow “rigorous evaluations of the scientific and clinical data” to ensure safe and effective treatment.