EU/3/08/595

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Orphan designation

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 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 and subsequently to Takeda Pharma A/S, Denmark, in October 2013.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is anaplastic large cell lymphoma?

Anaplastic large-cell lymphoma (ALCL) is a cancer of white blood cells called T lymphocytes. The characteristic of ALCL is the presence of blood cells expressing a specific molecule called CD30 on their surface. ALCL cells can be found both in the lymph nodes (nodal), as well as outside the nodules (extranodal locations). The first sign of the condition is often a painless swelling in the neck, armpit or groin, caused by enlarged lymph nodes. Often, more than one group of nodes is affected.

This lymphoma may also occur in skin, lungs, liver, bone marrow or bones. Some people experience loss of appetite and tiredness. Other symptoms, known as B symptoms, include night sweats, unexplained high temperatures, and weight loss. ALCL is a life-threatening disease.

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

At the time of designation, anaplastic large cell lymphoma affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 people*, and is below the threshold 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?

Anaplastic large-cell lymphoma is usually treated with intensive chemotherapy (using drugs to kill cancer cells). More than one chemotherapy drugs are often used for ALCL (combination chemotherapy). Radiotherapy (using high-dose x-rays or other high-energy rays to kill cancer cells) may be used alone at first stages of the disease, when the lymphoma cells are contained in one area of lymph nodes. However, radiotherapy is more commonly given after chemotherapy.

The monoclonal antibody against CD30 covalently linked to the cytotoxin monomethylauristatin E could be of significant benefit for the treatment of ALCL. The main reasons are that it may offer a new way of targeting and killing cancer cells and it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

CD30 is a molecule that Hodgkin lymphoma cells have on their surface (surface marker). One part of the medicinal product is an antibody against CD30 (anti-CD30), therefore is able to recognise and bind to CD30. The antibody is linked to a small molecule called monomethyl auristatin E, which is cytotoxic (kills rapidly dividing cancer cells). The CD30 antibody part of the product acts as a carrier for the cytotoxic substance. The product is thought to bind specifically on CD30 receptor of the lymphoma cells. Once bound on the cell surface, it is taken up by the cells. Once inside the cancer cells, the cytotoxic molecule, monomethyl auristatin E, gets released and stops cell division. The cancer cells are then expected to undergo programmed cell death.

What is the stage of development of this medicine?

The effects of monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials in patients with anaplastic large cell lymphoma had been started.

At the time of submission, the monoclonal antibody against CD30 covalently linked to the cytotoxin monomethylauristatin E was not authorised anywhere in the world for anaplastic large cell lymphoma or designated as orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 October 2008 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;
  • 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

Product details for <p>Monoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E</p>
Active substanceMonoclonal antibody against human CD30 covalently linked to the cytotoxin monomethylauristatin E
Medicine NameAdcetris
Disease/conditionTreatment of anaplastic large cell lymphoma
Date of decision14/01/2009
OutcomePositive
Orphan decision numberEU/3/08/595

Review of designation

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 maintained.

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.

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

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%.

Prevalence of the condition

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.

Existence of other satisfactory methods of treatment

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.

Significant benefit over existing treatments

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.

Conclusions

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.

Sponsor’s contact details:

Takeda Pharma A/S
Langebjerg 1
4000 Roskilde
Denmark
Tel. +45 46 77 1036
Fax: +45 46 75 6640

Patients’ associations contact points:

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.