EMA has recommended granting a marketing authorisation in the EU for Breyanzi (lisocabtagene maraleucel), a gene therapy for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B), whose cancer has come back or who have not responded to treatment after two or more lines of systemic therapy.

DLBCL, PMBCL and FL3B are subtypes of non-Hodgkin lymphoma, a cancer of the lymphatic system that begins in B-cells, a subtype of the white blood cells of the immune system, and can grow into tumours in the lymph nodes or in other places in the body, causing serious problems in the immune system, and in the organ in which they are growing.

Approximately 50% to 60% of patients achieve a long-term response and will be cured of the disease with standard-of-care immune-chemotherapy. However, the treatment of patients who do not respond to standard therapy or whose cancer has come back after previous treatments remains challenging and they require alternative options to improve their health outlook.

Breyanzi is an advanced therapy medicinal product (ATMP) belonging to a new generation of personalised immune-cell-based-gene-therapies that are based on collecting and genetically modifying a patient’s own immune cells to treat their cancer.

To create each dose of Breyanzi, the patient’s blood is extracted and its T-cells, a type of white blood cell that helps the body fight infection, are collected and genetically engineered to have a specific protein (chimeric antigen receptor, CAR) that helps the body recognise and eliminate cancerous B-cells. These modified immune cells are then infused back into the patient. The safety of Breyanzi was studied in four studies involving over three hundred treated patients and the efficacy in two studies pooling about three hundred and fifty enrolled patients. The efficacy studies concluded that clinical benefit would be expected with a meaningful disease control in a substantial proportion of patients.

Although Breyanzi is overall well tolerated, it can cause severe side effects, particularly cytokine release syndrome (CRS). This 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.

Breyanzi was supported through EMA’s PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support for promising medicines with a potential to address unmet medical needs.

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 Breyanzi outweighed the possible risks in patients with relapsed or refractory DLBCL, PMBCL and FL3B.

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 the CHMP is an intermediary step on Breyanzi’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.

Notes:

  1. The applicant for Breyanzi is Bristol-Myers Squibb Pharma EEIG
  2. Breyanzi was accepted into the PRIME scheme on 16 December 2016.
  3. Breyanzi was designated as an orphan medicinal product for the treatment of diffuse large B-cell lymphoma on 17 July 2017, for the treatment of follicular lymphoma on 25 May 2018 and for the treatment of primary mediastinal large-B-cell lymphoma on 19 November 2018.

Share this page