The European Commission ( EC ) has approved the first two marketing authorisations for chimeric antigen receptors ( CAR ) T-cells medicines in the European Union ( EU ).
Kymriah ( Tisagenlecleucel ) and Yescarta ( Axicabtagene ciloleucel ) are advanced therapies for blood 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.
Kymriah and Yescarta are also the first medicines supported through EMA’s PRIority MEdicines ( PRIME ) scheme to receive positive opinions from the Committee for Medicinal Products for Human Use ( CHMP ).
The voluntary scheme provides early and enhanced scientific and regulatory support to medicines that have the potential to address, to a significant extent, patients’ unmet medical needs.
Kymriah was granted eligibility to PRIME on 23 June 2016, for the treatment of acute lymphoblastic leukaemia ( ALL ). Yescarta was granted eligibility to PRIME on 26 May 2016 for the treatment of diffuse large B-cell lymphoma ( DLBCL ).
Because Kymriah and Yescarta are advanced-therapy medicinal products ( ATMPs ), they were assessed by the CHMP and the CAT, the Agency’s expert committee for cell-, gene- or tissue-based medicines which is responsible for the evaluation of these products.
The CAT adopts an advisory opinion, which is taken into account by the CHMP when giving its recommendation regarding the authorisation of the medicine concerned.
Innovative treatments such as CAR-T cells have potential to change the outlook for patients with cancer, but they also come with new scientific and regulatory challenges.
The main safety concerns related to the administration of CAR-T cells 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, and neurologic toxicities. Both 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.
CRS can be treated successfully with RoActemra ( Tocilizumab ).
Another important risk management measure for Kymriah and Yescarta is the utilisation of a patient registry to monitor the long-term safety and efficacy of these therapies, as a condition for the marketing authorisation.
Kymriah is indicated for the treatment of paediatric and young adult patients ( up to 25 years of age ) with B-cell ALL that is refractory or in second or later relapse, and in adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy.
Yescarta is indicated for the treatment of adult patients with relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma ( PMBCL ), after two or more lines of systemic therapy. ( Xagena )
Source: EMA, 2018