EU/3/09/650

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Orphan designation

On 24 July 2009, orphan designation (EU/3/09/650) was granted by the European Commission to Micromet AG, Germany, for blinatumomab for the treatment of acute lymphoblastic leukaemia.

In January 2012, Micromet AG changed name to Micromet GmbH. In May 2012, Micromet GmbH changed name to Amgen Research (Munich) Gmbh.

The sponsorship was transferred to Amgen Europe BV, The Netherlands, in February 2014.

Update: Blinatumomab (Blincyto) has been authorised in the EU since 23 November 2015 for treatment of adults with Philadelphia chromosome negative relapsed or refractory B-precursor acute lymphoblastic leukaemia.

What is acute lymphoblastic leukaemia?

Acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells called lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so there are too many of them circulating in the blood. These abnormal lymphocytes are not fully developed and do not work properly. Over a period of time, they replace the normal white cells and red blood cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body).

ALL is the most common type of leukaemia in young children, but the disease also affects adults, especially those aged 65 years and older. Many people with ALL can be cured. However, despite the available treatments, ALL remains a serious and life-threatening disease in some patients.

What is the estimated number of patients affected by the condition?

At the time of designation, acute lymphoblastic leukaemia affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).


*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

What treatments are available?

Treatment for ALL is complex and depends on a number of factors including the extent of the disease, whether it has been treated before, and the patient’s age, symptoms and general state of health. At the time of designation, the main treatment of ALL was chemotherapy (medicines used to kill cancer cells) followed by or combined with radiotherapy (using radiations to kill cancer cells). Bone-marrow transplantation was also used. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow from a matched donor.

The sponsor has provided sufficient information to show that blinatumomab might be of significant benefit for patients with ALL because it works in a different way to existing treatments and preliminary studies indicate that it may be an alternative to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Blinatumomab is a monoclonal antibody (a type of protein) that has been designed to specifically recognise and attach to the following proteins:

  • CD19, a protein that is found on the surface of ALL cells;
  • the ‘T-cell-receptor/CD3 complex’, which is responsible for the activation of some cells of the immune system (the body’s natural defences) called T cells.

By attaching to the cancer cells and the T-cell-receptor/CD3 complex, the medicine is expected to stimulate the T cells to kill the cancer cells.

What is the stage of development of this medicine?

The effects of blinatumomab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with ALL were ongoing.

At the time of submission, blinatumomab was not authorised anywhere in the EU for ALL. Orphan designation of blinatumomab had been granted in the United States for ALL. 

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2009 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • the seriousness of the condition;
  • the existence of alternative methods of diagnosis, prevention or treatment;
  • either the rarity of the condition (affecting not more than 5 in 10,000 people in the Community) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Product details for <p>Blinatumomab</p>
Active substanceBlinatumomab
Medicine Name
Disease/conditionTreatment of acute lymphoblastic leukaemia
Date of decision24/07/2009
OutcomePositive
Orphan decision numberEU/3/09/650

Review of designation

During its meeting of 6 to 8 October 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/09/650 for Blincyto (blinatumomab) as an orphan medicinal product for the treatment of acute lymphoblastic leukaemia. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with acute lymphoblastic leukaemia. The COMP recommended that the orphan designation of the medicine be maintained1.


1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Blincyto for:

‘adults with Philadelphia chromosome negative relapsed or refractory B-precursor acute lymphoblastic leukaemia’.

This falls within the scope of the product’s designated orphan indication, which is: ‘acute lymphoblastic leukaemia’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. Acute lymphoblastic leukaemia remains a condition that is life threatening, particularly due to a poor long-term prognosis if the cancer comes back after treatment.

Prevalence of the condition

The sponsor provided updated information on the prevalence of acute lymphoblastic leukaemia based on data from cancer registries (EUCAN 2012, GLOBOCAN 2012 and NORDCAN 2012).

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of acute lymphoblastic leukaemia remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be 1.8 people in 10,000. This is equivalent to a total of 92,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of acute lymphoblastic leukaemia, including clofarabine, dasatinib, imatininb, ponatinib and xaluprine mercaptopurine.

Significant benefit of Blincyto

The COMP concluded that the claim of a significant benefit of Blincyto in acute lymphoblastic leukaemia is justified because Blincyto has been shown to improve the outcome of a subset of patients with the disease for whom standard treatments do not usually work. The patients in this subset are Philadelphia chromosome negative (Ph-), which means that they have acute lymphoblastic leukaemia but do not have an abnormal rearrangement of their genes called the Philadelphia chromosome that is seen in some other patients with the condition.

This is based on a main study in 189 patients with Ph- B-cell acute lymphoblastic leukaemia whose disease had come back after, or had not responded to, previous treatment, and which showed that 42.9% (81 out of 189) of patients given Blincyto responded to treatment.

Therefore, although other methods for the treatment of acute lymphoblastic leukaemia have been authorised in the EU, the COMP concluded that Blincyto is of significant benefit to patients with this condition.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Blincyto still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Amgen Europe BV
Minervum 7061
4817 ZK Breda
The Netherlands
Tel. +31 765 732000
Fax +31 765 732001
http://www.amgen.nl/dutch/contact_us/amgen_contact.jsp

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.