EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Tecartus (autologous anti-CD19-transduced CD3+ cells) for the treatment of adult patients with a rare cancer of white blood cells called mantle cell lymphoma (MCL) when the symptoms or the disease come back (relapse) or when they are not responding (refractory) after two or more lines of systemic therapy.
Tecartus is the third CAR1-T cell medicine to be recommended for approval in the EU. CAR-Ts are advanced therapies for cancer, they belong to a new generation of personalised cancer immunotherapies that are based on collecting and modifying patients’ own immune cells to treat their cancer.
MCL is an aggressive subtype of non-Hodgkin lymphoma (NHL) which develops from abnormal B lymphocytes (B cells), a type of white blood cell. Its name derives from the fact that these cells originate from an area called the ‘mantle zone’ in lymph nodes.
The current standard of care for MCL includes treatment with stem cells taken from the patient’s own body and a number of different therapy regimens. While patients with MCL can respond well to initial treatments, it is common that their disease returns or that they no longer respond to treatment.
There are some therapeutic options for patients with refractory/relapsed MCL, including a class of medicines known as Bruton’s Tyrosine Kinase (BTK) inhibitors. However, treatment of patients with these forms of the disease is challenging due to the development of resistance to chemotherapy. Therefore, there is an unmet medical need for these patients.
To create each dose of Tecartus, the patient’s blood is extracted and its T-cells, a type of white blood cell that help the body fight infection, are collected and genetically engineered to have a specific protein (chimeric antigen receptor CAR-T) that helps the body recognise and eliminate lymphoma cells. These modified immune cells are then infused back into the patient.
The safety and efficacy of Tecartus was studied in a multicentre clinical trial of adult patients with refractory or relapsed MCL. 74 patients received Tecartus with a 12-month follow-up that highlighted an objective response rate (ORR), i.e. the proportion of patients who experienced a certain tumour size reduction, of 84%, and a complete response, i.e. the disappearance of signs of cancer, of 59%.
The most common side effects are cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, infections and encephalopathy, i.e. a brain disorder. The consequences of CRS can be life-threatening and, in some cases, even fatal. Monitoring and mitigation strategies for these side effects are described in the product information and in the risk management plan that is an integral part of the authorisation.
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 Tecartus outweighed the possible risks in the treatment of refractory/relapsed MCL in patients who had received more than two prior therapy regimens including BTK inhibitors.
The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended a conditional approval for this medicine. This is 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, in cases where 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.
Additional efficacy and safety data are being collected through the submission of long-term follow-up data from the main study and through a registry-based study that will also collect data on the long-term efficacy and safety of the medicine in specific subgroups (elderly, females, patients with severe disease).
Tecartus 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. Tecartus was granted eligibility to PRIME in June 2018 for the treatment of adult patients with relapsed or refractory mantle cell lymphoma.
The opinion adopted by the CHMP is an intermediary step on Tecartus’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/use of this medicine in the context of the national health system of that country.
1 Chimeric antigen receptor