EMA Recommends Granting Marketing Authorisations for the First Two CAR T-cell Therapies in the EU

It also recommended an extension to indications for tocilizumab to include the treatment of CAR-T-cell-induced cytokine release syndrome

On 28 June 2018, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisations for the first two chimeric antigen receptors (CAR) T-cell therapies in the European Union.  Tisagenlecleucel (Kymriah) and  ciloleucel (Yescarta) are both advanced therapy medicinal products (ATMPs). Kymriah is intended for the treatment of relapsed or refractory acute lymphoblastic leukaemia (ALL) and relapsed or refractory diffuse large B-cell lymphoma (DLBCL), while Yescarta is intended for treatment of relapsed or refractory DLBCL and relapsed or refractory primary mediastinal B-cell lymphoma (PMBCL). 

Kymriah and Yescarta were designated as orphan medicines during their development. They are also the first medicines supported through EMA’s PRIority Medicines (PRIME) scheme to receive a positive opinion from the CHMP. 

Together with the approval recommendation for the first CAR-T cell therapies, the CHMP also recommended an extension to the therapeutic indication for tocilizumab (RoActemra) to include the treatment of CAR-T-cell-induced cytokine release syndrome (CRS), a known serious side effect of CAR-T cell therapies. 

Tisagenlecleucel 

On 28 June 2018, the CHMP adopted a positive opinion, recommending granting a marketing authorisation for the medicinal product tisagenlecleucel (Kymriah). As Kymriah is an ATMP, the CHMP positive opinion is based on an assessment by the EMA Committee for Advanced Therapies (CAT). 

Kymriah, which was designated as an orphan medicinal product on 29 April 2014, was reviewed under EMA’s accelerated assessment programme. 

The applicant for this medicinal product is Novartis Europharm Limited. 

Kymriah will be available as a dispersion for infusion. The active substance of Kymriah is tisagenlecleucel, an autologous, immunocellular cancer therapy which involves reprogramming a patient’s own T cells to identify and eliminate CD19-expressing cells. This is achieved by addition of a transgene encoding a CAR. 

The benefits of Kymriah are its ability to achieve remission with a significant duration in patients with ALL and to achieve an objective response with a significant duration in patients with DLBCL. 

The most common side effects in patients with ALL are CRS, infections, hypogammaglobulinaemia, pyrexia and decreased appetite. 

The most common side effects in patients with DLBCL are CRS, infections, pyrexia, diarrhoea, nausea, hypotension and fatigue. 

The full indication is: 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, in relapse post-transplant or in second or later relapse and adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy. 

It is proposed that Kymriah be administered in a qualified treatment centre. Therapy should be started and supervised by a healthcare professional experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with Kymriah. 

Axicabtagene ciloleucel 

On 28 June 2018, the CHMP adopted a positive opinion, recommending granting a marketing authorisation for the medicinal product axicabtagene ciloleucel (Yescarta). As Yescarta is an ATMP, the CHMP positive opinion is based on an assessment by the EMA CAT. 

Yescarta, which was designated as an orphan medicinal product on 16 December 2014, was reviewed under EMA’s accelerated assessment programme. 

The applicant for this medicinal product is Kite Pharma EU B.V. 

Yescarta will be available as a dispersion for infusion. The active substance of Yescarta is axicabtagene ciloleucel, an autologous, immunocellular cancer therapy which involves reprogramming a patient’s own T cells to identify and eliminate CD19-expressing cells. This is achieved by addition of a transgene encoding a CAR. 

The benefits with Yescarta are its ability to achieve an objective response with a significant duration in patients with DLBCL and PMBCL. 

The most common side effects are CRS, infections, pyrexia, diarrhoea, nausea, hypotension and fatigue. 

The full indication is: Yescarta is indicated for the treatment of adult patients with relapsed or refractory DLBCL and PMBCL, after two or more lines of systemic therapy. 

It is proposed that Yescarta be administered in a qualified treatment centre. Therapy should be started and supervised by a healthcare professional experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with Yescarta. 

Tocilizumab 

On 28 June 2018, the CHMP adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product tocilizumab (RoActemra). 

The marketing authorisation holder for this medicinal product is Roche Registration GmbH. 

The CHMP adopted a new indication as follows: RoActemra is indicated for the treatment of CAR T cell-induced severe or life-threatening CRS in adults and paediatric patients 2 years of age and older. 

Detailed recommendations for the use of all three products will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission. 

Summaries of positive opinions are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinions.