Written by: Ashley C. Morales & Jane Dai, Ph.D.

On December 8, 2023, the U.S. Food and Drug Administration (FDA) approved two new gene therapies for the treatment of sickle cell disease.[1] The first, Casgevy™ (exagamglogene autotemcel (exa-cel)), is the first-ever approved cell-based gene editing therapy to be used in humans, and was developed in joint partnership between Vertex Pharmaceuticals and CRISPR Therapeutics.[2] Casgevy™ is indicated for the treatment of sickle cell disease in patients 12 years and older with recurrent vaso occlusive crises (VOCs).[3] The second, Lyfgenia™ (lovotibeglogene autotemcel (lovo-cel)), is developed by bluebird bio, and is indicated for the treatment of patients 12 years or older with sickle cell disease and a history of vaso-occlusive events (VOEs).[4]

Sickle cell disease is an inherited blood disorder caused by a single mutated gene. The mutation results in red blood cells that are hard and sticky, and in the form of shapes like sickles or crescents. These red blood cells then get caught in blood vessels, blocking the blood vessels.[5] Sickle cell disease can cause severe pain and organ damage, and can lead to life-threatening disabilities or death. Sickle cell disease disproportionately occurs among people of African, Middle Eastern and Indian descent, affecting millions around the world and about 100,000 in the U.S.[6]

Casgevy™ uses CRISPR, a Nobel Prize-winning gene editing tool, to snip the patients’ DNA.[7] Treatment with Casgevy™ involves collecting a patients’ bone marrow stem cells over a period of months. Once the stem cells are collected, they are sent to a gene editing facility, where the cells are edited with CRISPR over a sixteen-week period. These edited cells are shipped back to the patient’s hospital, where they are infused into a patient after treatment with chemotherapy.² When infused, the modified stem cells engraft within the bone marrow and increase the production of fetal hemoglobin (HbF), which prevents the sickling of red blood cells.¹

Lyfgenia™ is a cell based gene therapy which uses lentiviral vector (gene delivery vehicle) for genetic modification. Lyfgenia™ involves genetically modifying a patient’s blood stem cells to produce HbA^T87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, the normal hemoglobin produced in healthy adults. The modified stem cells are delivered to the patient as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant after treatment with chemotherapy.¹

While both treatments are a promising step in the treatment of sickle cell disease, both treatments are expected to be very expensive. It is estimated that the price for each could be over $ 2 million per patient.² It is still unclear whether insurers, especially government services such as Medicaid, will cover the therapies, due to the technical complexity and intense nature of the treatments.

Editor: Brenden S. Gingrich, Ph.D.

[1] See https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

[2] https://www.nytimes.com/2023/12/08/health/fda-sickle-cell-crispr.html

[3] See https://www.fda.gov/vaccines-blood-biologics/casgevy

[4] Seehttps://www.fda.gov/vaccines-blood-biologics/lyfgenia

[5] See https://www.cdc.gov/ncbddd/sicklecell/facts.html

[6] See https://www.npr.org/sections/health-shots/2023/12/08/1217123089/fda-approves-first-gene-editing-treatments-for-human-illness

[7] https://www.nobelprize.org/prizes/chemistry/2020/press-release/