EU/3/13/1115

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Orphan designation

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.

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 27,000 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. This represents a population of 509,000,000 (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.

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.

Key facts

Product details for <p>1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one</p>
Active substance1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4 d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one
Medicine Name
Disease/conditionTreatment of mantle-cell lymphoma
Date of decision12/03/2013
OutcomePositive
Orphan decision numberEU/3/13/1115

Review of designation

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.


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.

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

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

‘treatment of adult patients with relapsed or refractory mantle cell lymphoma’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of mantle cell lymphoma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2013. Mantle cell lymphoma remains a debilitating and life-threatening condition that progresses quickly and is associated with poor overall survival.

Prevalence of the condition

The sponsor provided information on the prevalence of mantle cell lymphoma based on data from the GLOBOCAN 2008 database.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of mantle cell lymphoma 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 still estimated to be less than 0.6 people in 10,000. This is equivalent to a total of fewer than 31,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, patients with mantle cell lymphoma were treated with chemotherapy (medicines to treat cancer) combined with monoclonal antibodies. Temsirolimus was specifically authorised in the EU for the treatment of relapsed or refractory mantle cell lymphoma (i.e. mantle cell lymphoma that has come back after previous treatment or has not responded to other treatments). Autologous haematopoietic (blood) stem-cell transplantation was used in some patients for whom it was suitable (this is a complex procedure where patients receive their own stem cells to help restore the bone marrow).

Significant benefit of Imbruvica

The COMP concluded that the claim of a significant benefit of Imbruvica in mantle cell lymphoma is justified by data showing that in patients with relapsed or refractory mantle cell lymphoma, a group with poor prognosis, treatment with Imbruvica significantly prolonged patient’s overall survival (how long they lived) and progression-free survival (how long they lived without their disease getting worse). In addition, the COMP noted that Imbruvica has the advantage of being available as capsules that can be taken by mouth at home unlike current treatments that are given by injection in hospital.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Imbruvica is of significant benefit to patients affected by mantle cell lymphoma.

Conclusions

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

Further information on the current regulatory status of Imbruvica can be found in the European public assessment report (EPAR).

Sponsor's contact details

Turnhoutseweg 30
B-2340 Beerse
Belgium
Tel. +44 (0)1494 658540
Fax +44 (0)1494 658540
E-mail: ybutt@its.jnj.com

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.