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Orphan designation

On 23 February 2011, orphan designation (EU/3/10/840) was granted by the European Commission to SymbioTec GmbH, Germany, for recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 for the treatment of acute lymphoblastic leukaemia.

The sponsorship was transferred to Xenetic Biosciences Plc, United Kingdom, in October 2012.

What is acute lymphoblastic leukaemia?

Acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells called lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so there are too many of them circulating in the blood. These abnormal lymphocytes are not fully developed and do not work properly. Over a period of time, they replace the normal white blood cells, red blood cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body).

ALL is the most common type of leukaemia in young children, but the disease also affects adults, especially those aged 65 years and older. Many people with ALL can be cured. However, despite the available treatments, ALL remains a serious and life-threatening disease in some patients.

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

At the time of designation, ALL affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 507,700,000 (Eurostat 2011).

What treatments are available?

Treatment for ALL 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. At the time of designation, the main treatment for ALL was chemotherapy (medicines to treat cancer) followed by or combined with radiotherapy (treatment with radiation). Haematopoietic (blood) stem-cell transplantation was also used. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

The sponsor has provided sufficient information to show that recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 might be of significant benefit for the treatment of ALL because it works in a different way to existing treatments and early studies show that it may improve the treatment of patients with ALL. 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?

Histones are proteins that are involved in ‘coiling up’ strands of DNA in cells into tightly packed chromosomes. Normally, they are only present within the nucleus of the cells, but cancer cells have been shown to also have histones on their surface. This medicine is made up of human histone H1.3, which is expected to attach to the histones on the surface of the cancer cells, forming large ‘aggregates’ (clumps) that cause the cell wall to break. This is expected to kill the cancer cells.

The medicine contains two types of histone H1.3, one that is identical to the human protein, and one (the ‘N-bis-met’ type) that is transformed in the body into the human protein. Both types of histone H1.3 in the medicine have been made using ‘recombinant DNA technology’: they are made by a bacterium that has received a gene that makes it able to produce them in large quantities.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3 in patients with ALL had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for ALL or designated as an 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 10 November 2010 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

Key facts

Product details for <p>Recombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3</p>
Active substanceRecombinant human histone H1.3 and recombinant human N-bis-met-histone H1.3
Medicine Name
Disease/conditionTreatment of acute lymphoblastic leukaemia
Date of decision23/02/2011
Orphan decision numberEU/3/10/840

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details:

Xenetic Biosciences Plc
London Bioscience Innovation Centre
2 Royal College Street
United Kingdom
Tel. +44 (0)20 7691 4906
Fax +44 (0)20 7916 9771

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.