The European Medicines Agency (EMA) has recently recommended the approval of the first therapy based in CRISPR/Cas9, a groundbreaking gene-editing technology that earned its inventors the Nobel Prize in 2020. This marks a significant milestone in the field of gene therapies. This medicinal product has also received approval from the Food and Drug Administration (FDA) for use in the US and from the Medicines and Healthcare Products Regulatory Agency (MHRA) for use in the UK.
Casgevy (exagamglogene autotemcel) is indicated for the treatment of transfusion-dependent beta thalassemia and severe sickle cell disease in cases where hematopoietic stem cell transplantation is appropriate, and a suitable donor is not available.
Beta thalassemia and sickle cell disease are two rare inherited disorders caused by genetic mutations that affect the production or function of hemoglobin, the protein responsible for carrying oxygen in red blood cells throughout the body. Both conditions are life-long debilitating and life-threatening, and the new therapy offers the potential to liberate patients from the burden of frequent transfusions and painful vaso-occlusive crises, which occur when sickled red blood cells obstruct small blood vessels. It has the potential to significantly enhance their quality of life.
For these reasons, Casgevy was designated as an orphan medicinal product in 2019 and 2020 for both indications. It was also accepted into the PRIME program, which provides early and enhanced scientific and regulatory support to medicines with the potential to address patients’ unmet medical needs.
Casgevy is a cell-based gene therapy medication produced using CRISPR/Cas9 technology to modify patients’ blood stem cells. It is a personalized, one-time treatment that involves mobilizing bone marrow stem cells from a patient’s blood. The CRISPR gene-editing process targets a specific DNA sequence inside the cell, using ‘molecular scissors’ to make precise cuts, allowing for the addition, removal, or alteration of genetic material at that specific location within the cell’s genome.
With Casgevy, stem cells are edited at the erythroid-specific enhancer region of the BCL11A gene, preventing the production of fetal hemoglobin (HbF). These modified cells are then reintroduced into the patient, and the reduced transcription of the BCL11A gene leads to an increase in HbF production, thus providing functional hemoglobin.
The EMA based its recommendation on two ongoing clinical trials. In the first trial, 42 beta thalassemia patients received a single dose, and 39 remained transfusion-free for at least one year. In the second trial, involving 29 patients with severe sickle cell disease, 28 experienced no vaso-occlusive crisis episodes for at least 12 consecutive months. Safety was assessed in these two clinical trials and one long-term follow-up study, with the most common side effects including low white blood cell counts, febrile neutropenia, low platelet levels, liver disease, nausea, vomiting, headache, and mouth sores.
Casgevy has received a recommendation for conditional marketing authorization, a regulatory mechanism that facilitates early access to medicines addressing unmet medical needs, allowing for approval with less complete data than usual, provided the benefits of its availability to patients outweigh the risks. The company must now submit final results by August 2026 to confirm the efficacy and safety of Casgevy.
The opinion endorsed by CHMP represents an interim step in Casgevy’s journey towards patient access. The next phase involves the European Commission making a decision on an EU-wide marketing authorization..
Check the official EMA press release if you want to know more or to consult the complete updated information related to the medicinal product here.
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