Casgevy’s FDA Approval Marks New Era in Sickle Cell Therapy

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Introduction

In December of 2023, the U.S. Food and Drug Administration approved a new gene editing technology called Casgevy to help treat Sickle Cell Anemia (SCD) in patients ages twelve and older. This is the first FDA approved treatment that can cure SCD and marks a significant milestone in gene therapy history.

What is Sickle Cell Anemia?

SCD is a rare inherited blood disorder which affects the shape of red blood cells which carry oxygen throughout the body. For someone to have SCD, both their parents must be carriers of the SCD gene. If someone receives only one SCD gene, then they would have some sickle cells and some normal blood cells. When someone has SCD, their red blood cells are shaped like crescent moons, or sickles, when in reality they should be round and flexible. The flexibility of the cell allows it to move freely through blood vessels, but often the sickle shaped cells are sticky and rigid and can slow and block blood flow.

What Are the Symptoms of Sickle Cell Anemia?

Sickle shaped cells, because of their rigidity, break and die easily. Generally, red blood cells can live for up to 120 days and are replaced after, but sickle cells can only survive for 10-20 days, 6-12 times less than regular blood cells. When someone has a shortage of red blood cells, it is called anemia and can lead to fatigue since the body is not receiving the adequate amount of oxygen it needs.

Additionally, when these sickle cells block the flow of blood in blood vessels, it leads to episodes of extreme pain. These episodes could last for a few hours, weeks, and some require a hospital stay since these episodes have varying intensities. It also can cause chronic pain in bones and joints and other parts of the body. Since sickle cells block blood circulation, they also cause ones’ hands and feet to swell.

In the course of a hematopoietic (blood stem cell transplant), the patients’ own modified blood stem cells are used to make both products, which are then administered back as a single-dose infusion once. A patient’s own stem cells must be extracted prior to treatment, and high-dose chemotherapy known as myeloablative conditioning is required to eliminate bone marrow cells and replace them with the altered cells seen in Casgevy and Lyfgenia. A long-term research will monitor patients who got either Lyfgenia or Casgevy in order to assess the efficacy and safety of each medication.

Casgevy and Lyfgenia, two ground-breaking medications that represent the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years of age and older, were approved by the U.S. Food and Drug Administration On December 8. Moreover, Casgevy, one of these treatments, is the first FDA-approved medication to make use of a revolutionary form of genome editing technique, indicating a significant breakthrough in the field of gene therapy.

For individuals with sickle cell disease who have repeated vaso-occlusive crises and are 12 years of age or older, the cell-based gene therapy casgevy is licensed. The first treatment using CRISPR/Cas9, a kind of genome editing technology, to receive FDA approval is called Casgevy. Hematopoietic (blood) stem cells from patients are altered by CRISPR/Cas9 genome editing. Targeted DNA snipping with CRISPR/Cas9 allows precise editing (removal, insertion, or replacement) of the targeted DNA. Reimplanted into the patient, the altered blood stem cells engraft (attach and multiply) in the bone marrow to boost the synthesis of fetal hemoglobin (HbF), a form of hemoglobin that helps carry oxygen. Elevated HbF levels stop red blood cells from sickling in sickle cell disease patients.

Another type of Gene therapy based on cells is called Lyfgenia. Lyfgenia is licensed for the treatment of sickle cell disease individuals 12 years of age and older with a history of vaso-occlusive episodes. It modifies genetic material using a lentiviral vector, a gene delivery vehicle. In the case of Lyfgenia, the patient’s blood stem cells undergo genetic modification to provide HbAT87Q, a hemoglobin created from gene therapy that works similarly to hemoglobin A, the typical adult hemoglobin produced in people without sickle cell disease. HbAT87Q-containing red blood cells are less likely to sickle and obstruct blood flow. The patient is subsequently given these altered stem cells.

Moreover, SCD makes one more susceptible to infections. This is because sickle cells can damage the spleen, which leads to increased risk of infections. As a result, babies and children with this disease will receive several vaccinations and antibiotics to prevent them from getting these infections and viruses which could threaten their lives.