Revolutionary CRISPR gene editing is now a full part of medicine’s arsenal. The United States Food and Drug Administration (FDA) announced this Friday the approval of Casgevy, the first treatment that uses a novel type of genome editing technology, CRISPR, which allows the book to be rewritten. too. of life instructions to correct mistakes. The new treatment is used to treat sickle cell anemia in patients over 12 years of age. At the same time, the regulator approved the use of another cellular gene therapy, Lyfgenia, in this case conventional, for the same disease.
The gene editing treatment was submitted to the FDA’s requested review in October at the request of Boston-based laboratories Vertex Pharmaceuticals and the Swiss CRISPR Therapeutics. Together they designed a therapy based on genome editing against that blood disease: sickle cell anemia, a genetic malformation responsible for the deformation of red blood cells. It is one of the most frequent in the world, and affects millions of people, 100,000 in the United States alone. Every year about 300,000 children are born with this condition worldwide.
Sickle cell anemia is a group of inherited blood disorders. Its main problem is a mutation in hemoglobin, a protein found in red blood cells that delivers oxygen to the body’s tissues. This mutation causes the red blood cells, instead of the usual round shape, to get the silhouette of a crescent or sickle, which causes them to get stuck in the blood vessels and cause pain that is not consistent to develop a normal life. Most patients do not live beyond 40 or 50 years.
For those affected, approval of this treatment is a ray of hope. It uses CRISPR gene editing technology, which allows you to cut and paste the instruction book of the 3 billion letters of DNA that make up a person’s genome to correct mistakes. However, it is a very expensive and complicated therapy to administer, so it is only available to a privileged few. It is expected to cost millions of dollars, making its use almost impossible in less developed countries, where the incidence of the disease is higher.
The new treatment consists of taking blood stem cells from the bone marrow, isolating them in the laboratory and using the molecular scissors of CRISPR to cut the genome right at the position of the BCL11A gene, which turns off the production of fetal hemoglobin after birth. Cells automatically repair the damaged genome by rejoining its ends, but the gene is disabled. Then it’s time to kill all the diseased blood cells in the patient’s bone marrow with high-dose chemotherapy and transplant the patient with the modified stem cells themselves. It engrafts (adheres and proliferates) to the bone marrow and increases the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates the delivery of oxygen. Within weeks, a new generation of red blood cells filled with healthy fetal hemoglobin spread throughout the body. In patients with sickle cell anemia, increased HbF levels inhibit the formation of sickle red blood cells.
The safety and effectiveness of Casgevy was evaluated in a trial in adult and adolescent patients with SCD. Patients had a history of at least two serious episodes of vaso-occlusive events. The primary efficacy outcome was the absence of such serious events for at least 12 consecutive months during the 24-month follow-up. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluated, 29 (93.5%) achieved this result. All treated patients achieved a satisfactory graft and none experienced graft failure or rejection.
Common side effects are low levels of platelets and white blood cells, mouth ulcers, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache, and pruritus, according to the FDA.
In the October review, outside experts brought in by the FDA spent a seven-hour session not so much on the effectiveness or safety of exa-cel, but on whether the methods used by Vertex and CRISPR Therapeutics have the potential to create changes. in DNA. This is what is known as “off-target editing”: genetic modifications that can be harmless or harmful if they affect certain regions of the genome. For the US health regulator, a priority is to guarantee that the treatment does not have these unexpected side effects.
For its part, Lyfgenia is a traditional cellular gene therapy, if you can call it a very new treatment. Lyfgenia does not use CRISPR gene editing, but instead uses a lentiviral vector (gene delivery vehicle) for genetic modification. It is also approved for the treatment of patients over 12 years of age with sickle cell anemia and a history of vaso-occlusive episodes. With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene therapy-derived hemoglobin that acts similarly to hemoglobin A, which is the normal adult hemoglobin produced in the people who are not affected by sickle cell anemia. Red blood cells with HbAT87Q have a lower risk of blocking blood flow. These modified stem cells are administered to the patient.
Like Casgevy, the modified stem cells are returned to the patient in an infusion as part of a blood stem cell transplant. Before the treatment, the stem cells are taken from the patient, who must undergo high-dose chemotherapy to remove his cells from the bone marrow and replace them with regenerated ones. Patients receiving Casgevy or Lyfgenia will be followed in a long-term study to assess the safety and effectiveness of each product.
“Gene therapy holds the promise of offering more specific and effective treatments, especially for people with rare diseases where current treatment options are limited,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products at the Center for Gene Therapy. FDA Biological Evaluation and Research, in a statement. “These approvals represent an important medical advance in the use of new cellular gene therapies to treat potentially devastating diseases and improve public health,” said Peter Marks. , director of the FDA’s Center for Biologics Evaluation and Research.
You can follow MATERIA on Facebook, X and Instagram, or sign up here to receive our weekly newsletter.