This new therapy may free patients from the burden of frequent transfusions and painful vaso-occlusive crises that occur when sickled red blood cells block small blood vessels, and has the potential to significantly improve their quality of life.
Beta thalassemia and sickle cell disease (SCD) are two inherited rare diseases caused by genetic mutations that affect the production or function of haemoglobin, the protein found in red blood cells that carries oxygen around the body. Both diseases are life-long debilitating and life-threatening.
Casgevy is a cell-based gene therapy medicinal product using CRISPR/Cas9 technology to edit the patient's own blood stem cells. It is a personalised one-off treatment that involves mobilising bone marrow stem cells from a patient's blood. CRISPR gene-editing finds a specific sequence of DNA inside a cell. Using ‘molecular scissors’ to make precise cuts, it enables adding, removing or altering genetic material at that specific location of the genome of the cells. With Casgevy, stem cells are edited at the erythroid-specific enhancer region of the BCL11A gene which usually prevents the production of foetal haemoglobin (HbF). These modified cells are then infused back into the patient, and the reduction of BCL11A gene transcription leads to increase of HbF production thus providing functioning haemoglobin.
Casgevy was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.
EMA based its recommendation on two ongoing, single-arm trials in patients aged 12 to 35 years. In the first one, 42 patients, including 13 adolescents, with transfusion-dependent beta thalassemia who received a single dose, were included in the primary efficacy set. Of these 42 patients, 39 were transfusion-free for at least one year. In the second trial, 29 patients, including six adolescents, suffering from severe SCD, were included in the primary efficacy set. Of these 29 patients, 28 were free of vaso-occlusive crises (VOC) episodes for at least 12 consecutive months. Characterised by severe pain and organ damage, VOC is the leading cause of emergency department visits and hospitalizations for patients with SCD.
The safety of Casgevy was evaluated in the same two ongoing, single-arm trials and one long term follow-up study, in which 97 adolescent and adult patients with transfusion-dependent beta thalassemia or SCD were treated with the medicine.
The most common side effects are low white blood cell counts including febrile neutropenia, low level of platelets, liver disease, nausea, vomiting, headache and mouth sores. These events are due to the medicines required for the modified blood cells to engraft and replace the unmodified stem cells.
Casgevy is recommended for a conditional marketing authorisation, one of the EU’s regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.
In order to confirm the efficacy and safety of Casgevy, the company will have to submit the final results obtained from the currently ongoing pivotal trials by August 2026, as well as results from the ongoing long-term follow-up study and other studies that will be conducted with the product. Patients treated with Casgevy will be followed up for 15 years, to monitor the long-term efficacy and safety of this gene therapy. To further characterise the long-term safety and efficacy of the medicine, the company will also have to conduct and submit the results of a study based on data from a patient registry.
In its overall assessment of the available data, the Committee for Advanced Therapies (CAT), EMA's expert committee for cell and gene-based medicines, found that the benefits of Casgevy outweighed the possible risks in patients with beta thalassemia and sickle cell disease. The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended approval of this medicine.
The opinion adopted by CHMP is an intermediary step on Casgevy’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
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