EU/3/13/1115 - orphan designation for treatment of mantle cell lymphoma

1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one (ibrutinib)

Overview

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in October 2021 upon request of the marketing authorisation holder.

This medicine is now known as ibrutinib.

On 12 March 2013, orphan designation (EU/3/13/1115) was granted by the European Commission to Janssen-Cilag International N.V., Belgium, for 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one for the treatment of mantle-cell lymphoma.

1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one for treatment of mantle cell lymphoma has been authorised in the EU as Imbruvica since 21 October 2014.

What is mantle-cell lymphoma?

Mantle-cell lymphoma is an aggressive cancer of a type of white blood cell called B lymphocytes, or B cells. In mantle-cell lymphoma, the B cells multiply too quickly and live for too long, so there are too many of them in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin area, caused by an enlarged lymph node. Patients may also have fever, weight loss, tiredness and night sweats.

Mantle-cell lymphoma is usually diagnosed in people aged over 50 years. It is more common in men than women. Mantle-cell lymphoma is a long-term debilitating and life-threatening disease that is associated with poor overall survival.

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

At the time of designation, mantle cell lymphoma affected approximately 0.17 to 0.56 in 10,000 people in the European Union (EU). This was equivalent to a total of around 9,000 and 29,000 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).

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*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 28), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013)

What treatments are available?

At the time of designation, temsirolimus was specifically authorised in the EU for the treatment of mantle-cell lymphoma that has come back after previous treatment or has not responded to other treatments. The main treatments for mantle-cell lymphoma included chemotherapy (medicines to treat cancer), immunotherapy (medicines that stimulate the body's own immune system to kill the cancer cells) and radiotherapy (treatment with radiation). Haematopoietic (blood) stem-cell transplantation was also used. This is a complex procedure where patients receive stem cells to help restore the bone marrow.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with mantle cell lymphoma because early studies show that it might improve the outcome of patients whose disease does not respond to or has come back after previous treatment. 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?

This medicine is expected to work by blocking an enzyme called Bruton's tyrosine kinase (Btk), which is mostly found in B lymphocytes. Btk promotes survival of B lymphocytes and their migration to the organs where these cells normally divide. By blocking Btk, the medicine is expected to slow down the migration of B lymphocytes in mantle-cell lymphoma and to induce cell death, thereby delaying or stopping the progression of the disease.

The medicine is expected to be taken by mouth.

What is the stage of development of this medicine?

The effects of 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine including patients with mantle-cell lymphoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for mantle-cell lymphoma. Orphan designation of this medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 2013 recommending the granting of this designation.

Update: 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one, ibrutinib (Imbruvica) has been authorised in the EU since 21 October 2014 for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

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 EU) 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.

EU/3/13/1115: Public summary of opinion on orphan designation:1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one for the treatment of mantle-cell lymphoma

AdoptedReference Number: EMA/COMP/101688/2013 Rev. 1

Key facts

• Active substance:
  1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one (ibrutinib)
• Medicine name:
  Imbruvica
• Intended use:
  Treatment of mantle cell lymphoma
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/13/1115
• Date of designation:
  12/03/2013
• Sponsor:

  Janssen-Cilag International N.V; Turnhoutseweg 30; B-2340 Beerse; Belgium; Tel. [phone]; https://www.janssen-emea.com/contactus

Review of designation

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in October 2021 upon request of the marketing authorisation holder.

During its meeting of 2 to 4 September 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/13/1115 for Imbruvica (ibrutinib¹) as an orphan medicinal product for the treatment of mantle cell lymphoma. 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 mantle cell lymphoma. The COMP recommended that the orphan designation of the medicine be maintained².

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¹Previously known as 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H- pyrazolo [3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one.
²The 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.