EU/3/08/581

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Orphan designation

On 7 November 2008, orphan designation (EU/3/08/581) was granted by the European Commission to Glaxo Group Limited, United Kingdom, for ofatumumab for the treatment of chronic lymphocytic leukaemia.

What is chronic lymphocytic leukaemia?

Chronic lymphocytic leukaemia is a disease in which cancer cells are found in the blood and the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells, called “blasts”, which mature into several different types of blood cells with specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets support blood clotting. When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. Over a period of time these abnormal cells replace the normal white cells, red cells and platelets in the bone marrow, which reduces the number of normal cells in the blood and leads to anaemia, coagulation problems (bruising, haemorrhages) and repeated infections. There are several types of leukaemias. Chronic lymphocytic leukaemia is a cancer of a type of white blood cell called the B-lymphocyte. The lymphocytes multiply and live too long, so there are too many of them circulating in the blood. These leukaemic lymphocytes look normal, but they are not fully developed and do not work properly. Chronic lymphocytic leukaemia is the most common type of leukaemia; it mainly affects older people, being rare in people under the age of 40. Chronic lymphocytic leukaemia is chronically debilitating and life-threatening, due to the severe prognosis and the poor long-term survival for high-risk patients.

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

At the time of designation chronic lymphocytic leukaemia affected approximately 3.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 176,000 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 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 502,282,000 (Eurostat 2008).

What treatments are available?

Treatment for leukaemia is complex, and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the age, symptoms, and the general health of the patient. Some people with B-cell chronic lymphocytic leukaemia never have treatment, if their illness is not causing any symptoms and is progressing slowly. Treatment is often started only if and when the symptoms become troublesome. Current main treatment of chronic lymphocytic leukaemia is chemotherapy (using drugs to kill cancer cells). Several products were authorised for the condition in the Community at the time of submission of the application for orphan drug designation.

Ofatumumab could be of potential significant benefit for the treatment of chronic lymphocytic leukaemia, because it might act differently from other medicinal products. 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?

Ofatumumab is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific structure (called an antigen) that is found on certain cells in the body.

Ofatumumab has been designed to target an antigen called CD20, which is present on the surface of all B-lymphocytes. When ofatumumab binds to the antigen, this causes lysis (cell death). This is expected to help in chronic lymphocytic leukaemia by destroying the cancerous B-lymphocytes.

What is the stage of development of this medicine?

The effects of ofatumumab were evaluated in experimental models.

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

Ofatumumab was not authorised anywhere worldwide for chronic lymphocytic leukaemia or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 September 2008 recommending the granting of this designation.

Update: Ofatumumab (Arzerra) has been authorised in the EU since 19 April 2010 for the treatment of chronic lymphocytic leukaemia (CLL) in patients who are refractory to fludarabine and alemtuzumab.

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 5 in 10,000 people in the European Union) 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>Ofatumumab</p>
Active substanceOfatumumab
Medicine NameArzerra
Disease/conditionTreatment of chronic lymphocytic leukaemia
Date of decision07/11/2008
OutcomePositive
Orphan decision numberEU/3/08/581

Review of designation

During its meeting of 2-3 February 2010, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/08/581 for Arzerra (ofatumumab) as an orphan medicinal product for the treatment of chronic lymphocytic leukaemia (CLL). The COMP reviewed 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*.

* The 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 Arzerra for:

‘the treatment of chronic lymphocytic leukaemia (CLL) in patients who are refractory to fludarabine and alemtuzumab’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of chronic lymphocytic leukaemia’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2008. CLL remains a condition that is chronically debilitating and life threatening, in particular due to poor long-term survival in high-risk patients.

Prevalence of the condition

The sponsor informed the COMP that no changes to the prevalence of the condition had been reported since the orphan designation of Arzerra in 2008.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of CLL remains below the threshold 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 3.5 people in 10,000. This is equivalent to a total of around 177,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other treatments such as alemtuzumab and fludarabine were authorised in the EU for the treatment of CLL.

Significant benefit over existing treatments

Overall, the COMP concluded that the significant benefit of Arzerra in CLL is justified on the basis of a clinically relevant advantage, particularly in patients who are refractory to fludarabine and alemtuzumab. This is supported by data from clinical studies, which showed that the overall response rate was 58% in CLL patients refractory to fludarabine and alemtuzumab, and 47% in CLL patients refractory to fludarabine and with bulky lymphadenopathy.

In conclusion, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Arzerra is of significant benefit for patients with CLL.

Conclusions

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

Related information

Sponsor’s contact details:

Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex UB6 0NN
United Kingdom
Telephone: +44 20 84 22 34 34
Telefax: +44 20 84 23 44 01
E-mail: sally.e.bruce@gsk.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.