EMA Adopts a New Indication for Blinatumomab

Following re-examination procedure, EMA adopts a new indication in adults with B-precursor ALL in first or second complete remission with minimal residual disease

On 15 November 2018, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended an extension of therapeutic indication for blinatumomab (Blincyto). Blincyto is currently authorised to treat B-precursor acute lymphoblastic leukaemia (ALL), and the change concerns an extension of use in patients with residual cancer cells in the body after previous treatment. 

The marketing authorisation holder is Amgen Europe B.V. 

On 26 July 2018, the CHMP had originally adopted a negative opinion on the extension of the use of Blincyto in patients with residual cancer cells in the body after previous treatment. At the request of the company, the CHMP re-examined its opinion. Following the re-examination, the CHMP adopted a final positive opinion on 15 November 2018 recommending that the change to the marketing authorisation be granted for Blincyto, but requested the company to provide the results from ongoing studies once available. 

The CHMP adopted a new indication as follows: 

Blincyto is indicated as monotherapy for the treatment of adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. 

To support its application, the company presented data from a main study in 116 patients with residual cancer cells who were treated with Blincyto. The study did not compare Blincyto with any other treatment. It looked at how many patients no longer had measurable residual disease after one treatment cycle. 

The CHMP’s main concern that led to the initial negative opinion was that although Blincyto helped to reduce the amount of residual cancer cells in many patients, there is no strong evidence that it leads to improved survival. Given the uncertainty, the CHMP was of the opinion that the benefits of Blincyto in patients with residual B-precursor ALL cells did not outweigh its risks. The CHMP therefore recommended in July that the change to the marketing authorisation be refused. 

During the re-examination, the CHMP looked again at all the data and consulted a group of experts in cancer treatments. The CHMP agreed with the expert group’s conclusion that, although there is no strong evidence of patients living longer, the available data from the main study indicate a good response to Blincyto, with around 78% of patients not having measurable residual cancer cells after treatment. The Committee also considered that patients with minimal residual disease are at high risk of the disease coming back and have few treatment options. Therefore, the CHMP concluded that the benefits of Blincyto outweigh its risks and recommended granting the change to the marketing authorisation. However, the CHMP requested the company to provide further data from ongoing studies once available. 

The medicine has been authorised since November 2015 and contains the active substance blinatumomab. Blincyto was designated an orphan medicine (a medicine to be used in rare diseases) on 24 July 2009 for ALL. The active substance in Blincyto, blinatumomab, is an antibody that has been designed to recognise and attach to CD19 found on all B cells, including ALL cells. It also attaches to CD3 found on T cells. Blincyto therefore, acts as a bridge, bringing the T cells and the B cells together and causing the activation of T cells, which release substances that eventually kill B cells. 

For information, the full indications for Blincyto will be as follows: 

  • Blincyto is indicated as monotherapy for the treatment of adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor ALL. 
  • Blincyto is indicated as monotherapy for the treatment of adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with MRD greater than or equal to 0.1%. 
  • Blincyto is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics, which will be published in the revised European public assessment report and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.

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