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Orphan designation

On 10 October 2012, orphan designation (EU/3/12/1054) was granted by the European Commission to Roche Registration Limited, United Kingdom, for obinutuzumab for the treatment of chronic lymphocytic leukaemia.

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

What is chronic lymphocytic leukaemia?

Chronic lymphocytic leukaemia (CLL) is cancer of a type of white blood cell called B-lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so that there are too many of them circulating in the blood. The cancerous lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time, the abnormal cells replace the normal white cells, red cells and platelets (components that help the blood to clot) in the bone marrow (the spongy tissue inside the large bones in the body).

CLL is the most common type of leukaemia and mainly affects older people. It is rare in people under the age of 40 years. CLL is a long-term debilitating and life-threatening disease because some patients develop severe infections.

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

At the time of designation, CLL affected approximately 3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 153,000 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. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

What treatments are available?

Treatment for CLL is complex and depends on a number of factors, including the extent of the disease, whether it has been treated before, and the patient’s age, symptoms and general state of health. Patients whose CLL is not causing any symptoms or is only getting worse very slowly may not need treatment. Treatment for CLL is only started if symptoms become troublesome. At the time of designation, the main treatment for CLL was chemotherapy (medicines to treat cancer).

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with CLL because early studies suggest that it might improve the outcome of patients whose disease has come back after 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?

Obinutuzumab is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Obinutuzumab has been designed to target an antigen called CD20, which is present on the surface of all B-lymphocytes. When obinutuzumab attaches to the CD20, this is expected to cause cell death of the B-lymphocytes, improving the symptoms of the disease.

What is the stage of development of this medicine?

The effects of obinutuzumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with obinutuzumab in patients with CLL were ongoing.

At the time of submission, obinutuzumab was not authorised anywhere in the EU for CLL. Orphan designation of obinutuzumab had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 September 2012 recommending the granting of this designation.

Update: obinutuzumab (Gazyvaro) has been authorised in the EU since 23 July 2014. Gazyvaro in combination with chlorambucil is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy.

More information on Gazyvaro can be found in the European public assessment report (EPAR) on the Agency’s website.


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>Obinutuzumab</p>
Active substanceObinutuzumab
Medicine NameGazyvaro
Disease/conditionTreatment of chronic lymphocytic leukaemia
Date of decision10/10/2012
Orphan decision numberEU/3/12/1054

Review of designation

During its meeting of 10 to 12 June 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/12/1054 for Gazyvaro (obinutuzumab) as an orphan medicinal product for the treatment of chronic lymphocytic leukaemia (CLL). 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 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 CLL. The COMP recommended that the orphan designation of the medicine be maintained1.

1 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 Gazyvaro for:

‘treatment, in combination with chlorambucil, of adult patients with previously untreated chronic lymphocytic leukaemia and with co morbidities making them unable to tolerate a full-dose fludarabine based therapy’.

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

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. CLL remains a condition that is debilitating in the long term and life threatening, because patients may develop severe infections.

Prevalence of the condition

The sponsor provided updated information on the prevalence of CLL based on the most recent leukaemia IARC data (GLOBOCAN 2008) and data from the UK Office of National Statistics.

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 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 3 people in 10,000. This is equivalent to a total of around 153,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, the main treatment for CLL was chemotherapy (medicines to treat cancer), which might include chlorambucil or fludarabine-based therapy.

Significant benefit of Gazyvaro

The COMP concluded that the claim of a significant benefit of Gazyvaro in CLL is justified on the basis of it being more effective than existing treatments at improving the progression-free survival (the time patients lived without their disease getting worse) of previously untreated CLL patients.

This is based on a main study that showed that the average progression-free survival in patients treated with Gazyvaro plus chlorambucil (26.7 months) was significantly longer than the average progression-free survival with chlorambucil alone (11.1 months) or with chlorambucil plus rituximab (15.2 months).

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Gazyvaro is of significant benefit for patients affected by CLL.


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

Sponsor’s contact details

Roche Registration Limited
6 Falcon Way
Shire Park
Welwyn Garden City AL7 1TW
United Kingdom
Tel. +44 (0)1707 362840
Fax +44 (0)1707 377838

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.