The European Medicines Agency (EMA) has recommended a marketing authorisation in the European Union (EU) for Ebvallo (tabelecleucel) for the treatment of adult and paediatric patients who experience a serious complication following solid organ transplantation (SOT) or bone marrow transplantation (hematopoietic cell transplant - HCT) called EBV+ PTLD.
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This is one of the most important malignancies after transplantation. It is a result of the immunosuppression caused by the medication required to reduce the possibility of rejection of the transplanted organ or cells and the most common form of this condition is associated with the Epstein-Barr virus.
Ebvallo is indicated in patients after a transplant and who have received at least one prior therapy when the symptoms of the disease come back after treatment (relapsed) or when the treatment does not work (refractory).
A significant unmet need exists for patients who fail first-line therapies as they have only weeks to a few months’ survival after treatment failure, and other treatment options are limited. The aim of new treatments is to achieve the disappearance of all signs of cancer after treatment (complete remission) and prolong overall-survival, thereby reducing transplantation-related mortality of patients with EBV+ PTLD.
Tabelecleucel, the active substance of Ebvallo, targets and eliminates infected cells. It is an advanced therapy medicinal product made of cells of the immune system called T-cells that have been taken from a donor (allogeneic).
The T-cells are first mixed with another type of white blood cells in the immune system (B-cells) from the same donor that have been infected with the Epstein-Barr virus so that the T-cells learn to recognise infected B-cells. The T-cells are then grown to increase their numbers.
When the medicine is given to the patient, the T-cells are expected to attack and kill the patient's own infected B-cells, thereby helping to control cancers associated with the virus.
Ebvallo 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’s recommendation is based on the results of an ongoing multicentre, phase 3, single-arm, open-label clinical trial. The study investigated the efficacy and safety of tabelecleucel in 43 patients with relapsed/refractory EBV+ PTLD who had received at least one prior therapy.
Approximately half of the treated subjects achieved partial or complete remission. A significant number of patients enrolled in the study responded to the treatment with a durable response of six months or more without disease signs or symptoms after treatment.
The most common side effects are fever, diarrhoea, tiredness, feeling sick, low levels of red blood cells, decreased appetite and low blood sodium levels.
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 Ebvallo outweighed the risks in patients with EBV+ PTLD.
The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended approval of this medicine under exceptional circumstances.
A marketing authorisation under exceptional circumstances allows patients’ access to medicines that cannot be approved using a standard authorisation route as comprehensive data cannot be obtained under normal conditions of use.
Sometimes this is due to the small number of patients with the disease. In other cases, the collection of complete information on the efficacy and safety of the medicine is not possible or would be unethical. The medicines concerned are subject to specific post-authorisation obligations and monitoring.
The CHMP requested the applicant to submit data to further characterise the long-term efficacy and safety of patients enrolled in the clinical trials, and to conduct a post-authorisation observational safety study in patients treated with the medicine in Europe. The protocol must be submitted within three months of marketing authorisation.
The opinion adopted by the CHMP is an intermediary step on Ebvallo’s path to patient access. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on the 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/use of this medicine in the context of the national health system of that country. ■