2023-12-14 12:15:23
Sickle cell anemia is a group of inherited blood disorders that affect approximately more people than is believed. In the United States alone the figure rises to one hundred thousand people.
The main problem with sickle cell anemia is a mutation in hemoglobin, a protein found in red blood cells that supplies oxygen to the body’s tissues. This mutation causes red blood cells to develop a crescent or “sickle” shape. These sickled red blood cells restrict flow in blood vessels and limit oxygen delivery to the body’s tissues, causing severe pain and organ damage, known as vaso-occlusive episodes (VOEs) or seizures. vaso-occlusive (VOC). Recurrence of these events or crises can lead to life-threatening disabilities or premature death.
Recently, the US Food and Drug Administration (FDA) approved two important treatments, Casgevy and Lyfgenia. These are two pioneering cell-based gene therapies to treat sickle cell anemia in patients 12 years of age and older.
Casgevy is the first FDA-approved therapy that uses CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.
CRISPR/Cas9 technology can be targeted to cut DNA in specific areas, allowing the DNA to be precisely edited (deleted, added, or replaced) 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 anemia, elevated levels of HbF prevent sickle cell formation in red blood cells.
Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification. With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in people not affected by sickle cell anemia. Red blood cells containing HbAT87Q have a lower risk of sickle cell formation and blood flow occlusion. These modified stem cells are then given to the patient.
Both products are made from the patient’s own blood stem cells, which are modified and administered in a single application as part of a hematopoietic (blood) stem cell transplant.
Before treatment, the patient’s own stem cells are collected and then the patient has to undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with Casgevy-modified cells and Lyphgenia. Patients who received Casgevy or Lyfgenia will be followed long-term. The objective of this monitoring is to corroborate the safety and effectiveness of each product in the long term.
Artistic recreation of DNA segment, the material of the genome. (Illustration: Amazings/NCYT)
Data supporting Casgevy
The safety and effectiveness of Casgevy were evaluated in an ongoing, single-arm, multicenter study in adult and adolescent patients with sickle cell anemia. Patients had a history of at least two protocol-defined severe vaso-occlusive crises during each of the two years prior to screening. The primary efficacy outcome was the absence of severe episodes of vaso-occlusive crisis for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this result. All treated patients achieved successful engraftment and no patients experienced graft failure or rejection.
The most common side effects were low platelet and white blood cell levels, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache, and itching.
Data supporting Lyfgenia
The safety and effectiveness of Lyfgenia are based on analysis of data from a 24-month, single-arm, multicenter study in patients with sickle cell anemia and a history of vaso-occlusive event between the ages of 12 and 50 years. Efficacy was evaluated based on complete resolution of vaso-occlusive episodes between 6 and 18 months after application of Lyfgenia. Twenty-eight (88%) of 32 patients achieved complete resolution of vaso-occlusive episodes during this period.
The most common side effects included stomatitis (sores on the lips, mouth, and throat), low levels of platelets, white and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and the disease. underlying.
Some hematologic malignancies (blood cancer) have occurred in patients treated with Lyfgenia. This is warned on the product packaging. Patients receiving this product should undergo lifelong follow-up to detect these malignancies early if they arise. (Source: FDA)
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