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Orphan designation

Please note that this product was withdrawn from the Community register of designated orphan medicinal products in July 2013 on request of the sponsor.

On 24 July 2009, orphan designation (EU/3/09/658) was granted by the European Commission to Eudax S.R.L., Italy, for tamibarotene for the treatment of acute promyelocytic leukaemia.

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

What is acute promyelocytic leukaemia?

Acute promyelocytic leukaemia (APL) is a rare form of leukaemia, a cancer of the white blood cells (cells that fight against infections). APL is caused by a ‘chromosomal translocation’ (when there is a rearrangement of parts of genes between two chromosomes). The translocation affects the way the white blood cells grow. The cells also lack the ability to use retinoic acid (vitamin A).

In patients with APL, large numbers of abnormal, immature white blood cells called ‘blasts’ quickly build up in the bone marrow (the spongy tissue inside the large bones) and are found in the blood. APL is a life-threatening disease because these immature cells take the place of the normal white blood cells, reducing the patient’s ability to fight infections.

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

At the time of designation, APL affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 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 504,800,000 (Eurostat 2009).

What treatments are available?

Treatment for APL 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 APL was all-trans retinoic acid (ATRA), a medicine derived from vitamin A that helps the blasts to mature into normal white blood cells. This was used in combination with chemotherapy (medicines to kill cancer cells) in particular anthracyclines.

In some cases, bone-marrow transplantation was used. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow from a matched donor. In addition, arsenic trioxide (a medicine that causes death in APL cells) was used when patients had not responded to ATRA and chemotherapy, or when their disease had come back after these treatments.

The sponsor has provided sufficient information to show that tamibarotene might be of significant benefit for patients with APL because it might be more efficacious and cause fewer side effects than existing treatments. In addition, the medicine might be effective in patients who do not respond to ATRA. These assumptions 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?

Tamibarotene is a ‘synthetic retinoid’ (a substance that is related to vitamin A). Tamibarotene is expected to work by stimulating the blasts to mature into normal white blood cells by attaching to a protein on the cells called the retinoic acid receptor. Although this mechanism of action is similar to that of ATRA, tamibarotene could also work in patients who do not respond to ATRA because it may be less likely to activate another protein called ‘cellular retinoic-acid-binding protein’. This protein breaks vitamin-A-derived substances down and stops them working.

What is the stage of development of this medicine?

The effects of tamibarotene have been evaluated in experimental models.

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

At the time of submission, tamibarotene was authorised in Japan for the treatment of APL. Orphan designation of tamibarotene had been granted in the United States and Japan for APL.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 June 2009 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 Community) 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>Tamibarotene</p>
Active substanceTamibarotene
Medicine Name
Disease/conditionTreatment of acute promyelocytic leukaemia
Date of decision24/07/2009
Orphan decision numberEU/3/09/658

Review of designation

Sponsor’s contact details

Eudax Srl
Polo Tecnologico
Via Fratelli Cuzio, 42
27100 Pavia
Tel. +39 03 821 750 652
Fax +39 03 821 750 669

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.