EU/3/08/595: Orphan designation for the treatment of peripheral T-cell lymphoma

monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E

Overview
Key facts
Review of designation

Overview

On 15 January 2009, orphan designation (EU/3/08/595) was granted by the European Commission to Seattle Genetics UK Limited, United Kingdom, for monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E (brentuximab vedotin) for the treatment of anaplastic large cell lymphoma.

The sponsorship was transferred to Takeda Global Research and Development Centre (Europe) Ltd, United Kingdom, in September 2010.

Brentuximab vedotin for treatment of peripheral T-cell lymphoma has been authorised in the EU as Adcetris since 30 October 2012.

The sponsorship was transferred to Takeda Pharma A/S, Denmark, in October 2013.

On 21 August 2019 orphan designation EU/3/08/595 was granted by the European Commission to Takeda Pharma A/S, Denmark, for the amended indication: treatment of peripheral T-cell lymphoma.

The sponsor’s address was updated in August 2020.

: Peripheral T-cell lymphoma is a cancer of the lymphatic system, a network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream. In peripheral T-cell lymphoma there is uncontrolled growth of T lymphocytes (T cells), a type of white blood cell found in the lymphatic system. Peripheral T-cell lymphomas include types that mainly occur in the lymph nodes (primary nodal) and types that occur mainly outside the lymph nodes (primary extranodal).
The symptoms of the disease vary according to the type of lymphoma, but the first sign may be a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. The lymphoma may also affect other organs in the body such as the bone marrow, liver and the skin.
Peripheral T-cell lymphoma is a long-term debilitating and life-threatening condition because in most cases the disease does not respond well to therapy, usually comes back within one year and is associated with early death.

: At the time of designation, peripheral T-cell lymphoma affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 52,000 people¹, 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).
¹Disclaimer: 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. This represents a population of 518,400,000 (Eurostat 2019).

: At the time of designation, there were no specific treatments for peripheral T-cell lymphoma, but the disease was treated in the same way as the broader class of lymphomas known as non-Hodgkin's lymphomas, for which several medicines were authorised in the EU. The main treatment was chemotherapy (medicines to treat cancer), sometimes in combination with radiotherapy (treatment with radiation).
The sponsor has provided sufficient information to show that this medicine might be of benefit for patients with peripheral T-cell lymphoma because early studies showed that the medicine, used on its own, can be of benefit in patients whose disease had not improved with previous treatments or had come back after treatment. Studies also showed that patients lived longer when the medicine was used in combination with existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

: Peripheral T-cell lymphoma cells have a molecule on their surface called CD30. This medicine is made up of a CD30 monoclonal antibody (a type of protein that attaches to CD30), attached to monomethyl auristatin E, a cytotoxic (cell-killing) molecule. The monoclonal antibody delivers the cytotoxic molecule inside the CD30-positive cancer cells, which stops them from dividing and eventually causes their death.

: The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with peripheral T-cell lymphoma were ongoing.
At the time of submission, the medicine was authorised in the EU as Adcetris for the treatment of Hodgkin’s lymphoma, systemic anaplastic large cell lymphoma and CD30-positive cutaneous T-cell lymphoma. The medicine was not authorised anywhere in the EU for the treatment of peripheral T-cell lymphoma. Orphan designation of the medicine had been granted in the United States for this condition.
This medicine had been given orphan designation on 15 January 2009 for the treatment of anaplastic large cell lymphoma (EU/3/08/595). At the request of the sponsor and having assessed the additional data submitted, the COMP adopted a positive opinion on 18 July 2019 recommending the designation be amended to treatment of peripheral T-cell lymphoma.

the seriousness of the condition;
the existence of alternative methods of diagnosis, prevention or treatment;
and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Active substance	monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E
Medicine name	Adcetris
Intended use	Treatment of peripheral T-cell lymphoma
Orphan designation status	Positive
EU designation number	EU/3/08/595
Date of designation	21/09/2019
Sponsor	Takeda Pharma A/S Delta Park 45 2665 Vallensbaek Strand Hovedstaden Danmark Tel: +45 4677 1111 E-mail: kristina.stovring@takeda.com

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Adcetris at the time of change to the terms of the marketing authorisation, and confirmed that the orphan designation should be maintained.

More information is available in the orphan medicine assessment report.

During its meeting of 4-5 September 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/08/595 for Adcetris (brentuximab vedotin¹) as an orphan medicinal product for the treatment of anaplastic large cell lymphoma (ALCL). 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 satisfactory methods of treatment. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained².

¹Previously known as monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E.

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.

: The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Adcetris for the treatment of ‘relapsed or refractory systemic anaplastic large cell lymphoma’.
This falls within the scope of the product’s designated orphan indication(s), which is: ‘anaplastic large cell lymphoma’.
The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. ALCL remains a serious and life-threatening condition that is associated with a poor 5-year survival of 29-44%.

: The sponsor provided updated information on the prevalence on the basis of data from the Globocan 2002 database and updated population data. On the basis of the information provided by the sponsor and the knowledge of the COMP, the Committee concluded that the prevalence of ALCL 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 approximately 0.2 people in 10,000. This is equivalent to a total of around 10,000 people in the EU.

: At the time of the review of the orphan designation, other methods were authorised in the EU for the treatment of ALCL, including chemotherapy (medicines to treat cancer) and radiotherapy (treatment with radiations). More than one chemotherapy medicine was often used for ALCL (combination chemotherapy). Radiotherapy was commonly given after chemotherapy.

: The COMP concluded that the claim of significant benefit of Adcetris over existing treatments is justified on the basis of it being more effective at improving the survival of patients who did not respond any longer to other therapies.
This is based on data from a main study with Adcetris, showing a high response rate (proportion of patients who respond to treatment in terms of showing less/no signs of cancer) and a long progression-free survival (PFS, how long the patients lived without their disease getting worse) in patients who had no other treatment options. The data showed that for 60% of patients (35 out of 58) the PFS after Adcetris was equal or longer than the PFS after the previous treatment received by these patients. In addition, the prolonged survival seen with Adcetris could enable these patients, who generally have poor outcomes and lack suitable therapies, to undergo stem cell transplantation or other treatments that may stabilise the disease.
Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Adcetris is of significant benefit for patients affected by anaplastic large cell lymphoma.

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

Documents related to this orphan designation evaluation

EU/3/08/595: Public summary of positive opinion for orphan designation of monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E (brentuximab vedotin) for the treatment of peripheral T-cell lymphoma (PDF/217.32 KB)

First published: 16/01/2020
EMADOC-628903358-1297

Recommendation for maintenance of orphan designation at the time of marketing authorisation: Adcetris (brentuximab vedotin) for the treatment of anaplastic large cell lymphoma (PDF/107.28 KB)

Adopted

First published: 28/11/2012
Last updated: 28/11/2012
EMA/COMP/601842/2012

Patients' organisations

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

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

EU register of orphan medicines

The list of medicines that have received an orphan designation in the EU is available on the European Commission's website:

European Commission: Community Register of orphan medicinal products