World’s First Gene Therapies Approved to Treat Sickle Cell Disease

The U.S. Food and Drug Administration (FDA) has approved two treatments, Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. Casgevy is the first FDA-approved treatment to utilize CRISPR/Cas9, a novel genome editing technology, which signals an innovative advancement in the field of gene therapy. 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 SCD, increased levels of HbF prevent the sickling of red blood cells. 

Lyfgenia, a cell-based gene therapy, uses a lentiviral vector (gene delivery vehicle) for genetic modification and is approved for the treatment of patients 12 years of age and older with SCD and a history of vaso-occlusive events. 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 SCD. 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. 

Both products 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. Prior to treatment, patients’ own stem cells are collected, and then patients 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. Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness. 

“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, MD, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research. “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.”