The European Medicines Agency’s (EMA) Committee for Products for Human Use recommended on Friday that a breakthrough genetic treatment be used against two diseases caused by errors in the patient’s DNA. These are sickle cell anemia and beta thalassemia, which affect the blood and can lead to death in those affected.
The new method to address this is called “Casgevy,” a gene editing therapy using CRISPR/Cas9 technology. And its application would save patients from having to undergo frequent transfusions and suffering from the resulting vaso-occlusive crises, which occur when sickled red blood cells block small blood vessels. The quality of life of these people would therefore improve considerably.
Normally, people affected by these two diseases at the age of 12 or older usually undergo hematopoietic stem cell transplantation, but this is not always as fast as necessary due to the lack of suitable donors or because They are not available at this time. In these cases, the new therapy would be the ideal solution.
Two trials and few side effects
The EMA recommendation is based on two trials carried out on a group of patients aged 12 to 35. In the first case, 42 patients, including 13 adolescents, with transfusional beta-thalassemia who received a single dose were included in the main effectiveness set. Of these 42 patients, 39 have not received additional transfusions for at least one year. In the second trial, 29 patients, including six adolescents, with severe sickle cell anemia were included in the main efficacy set. Among these 29 patients, 28 were free from episodes of vaso-occlusive crises for at least 12 consecutive months.
what is it
A cellular gene therapy drug that uses CRISPR/Cas9 technology to modify the patient’s own blood stem cells. It is a unique and personalized treatment.
To evaluate it, Vertex will have to present the final results in August 2026. Patients treated in the trials will be followed for 15 years.
Low levels of white blood cells and platelets, liver disease, nausea, vomiting, headaches and mouth sores.
The safety of “Casgevy” was evaluated in these trials involving 97 people. And its main side effects were low levels of white blood cells and platelets, liver disease, nausea, vomiting, headaches and mouth sores. All, according to the EMA, are due to the drugs needed for lab-edited blood cells to engraft and replace unmodified ones.
The EC must authorize its marketing
The pharmaceutical company in charge of the trials, Vertex Pharmaceutical, was very satisfied with the institution’s recommendation. Its executive vice president, Nia Tatsis, said that “this positive opinion is another important medical milestone” that can improve the quality of patients with these two diseases.
Of course, the EMA’s recommendation does not constitute definitive approval for its use in affected individuals, but rather an interim step. It is now up to the European Commission (EC) to decide whether or not to authorize marketing in the EU. Through it, pricing and reimbursement decisions will be made by each Member State, taking into account the role or potential use of this medicine within its national health system.
Now available in the United States
Since 2018, the Spanish Agency for Medicines and Health Products (AEMPS), dependent on the Ministry of Health, has authorized four clinical trials in Spain with cells subjected to these promising genome editing techniques, three of them with CRISPR/Cas (the technology used in ‘Casgevy’) and one with the TALEN system (transcription activator-like effector nuclease).
In the United States, the U.S. Food and Drug Administration (FDA) approved the use of “Casgevy” earlier this month. In October, he took the exam from this body which, after two months of study and deliberation, decided to give him the green light. Meanwhile, a seven-hour session was dedicated to determining whether the methods used by Vertex and CRISPR Therapeutics pose a potential risk of making unwanted changes to DNA. For the American health regulator, it was a priority to ensure that this was not the case.
A unique and personalized treatment
“Casgevy” is a cellular gene therapy drug that uses CRISPR/Cas9 technology to modify the patient’s own blood stem cells. This is a unique and personalized treatment which involves mobilizing bone marrow stem cells from the patient’s blood. CRISPR gene editing makes it possible to detect a specific sequence of DNA in a cell. By using “molecular scissors” to make precise cuts, it allows genetic material to be added, removed or modified at that specific location in the cell’s genome.
Thus, stem cells are modified in the erythroid-specific enhancer region of the BCL11A gene which normally prevents the production of fetal hemoglobin (HbF). These modified cells are then reinjected into the patient and reduced transcription of the BCL11A gene results in increased production of HbF, thereby providing functional hemoglobin. This improves the patient’s quality of life.