EU/3/06/416

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Orphan designation

On 3 November 2006, orphan designation (EU/3/06/416) was granted by the European Commission to CanReg (Europe) Limited, Ireland, for antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' for the treatment of acute myeloid leukaemia.

The sponsorship was transferred to EleosInc Limited, United Kingdom, in May 2007.

What is acute myeloid leukaemia?

Leukaemia is a cancer of the blood-forming cells that starts in the bone marrow (the spongy tissue inside the large bones of the body) and spreads into the blood. Myeloid cells include cells that develop into granulocytes (certain cells that are part of the body’s natural defence system, the immune system) and platelets (components that help the blood clotting). Acute leukaemia is fast growing; the cells don’t stop dividing when normal cells would. General signs and symptoms of leukaemia include fatigue, weakness, weight loss, fever and loss of appetite. Symptoms specific to acute myeloid leukaemia are caused by a shortage of normal healthy blood cells, and include easily bruising or bleeding (result of platelet deficiency), shortness of breath, paleness, or fatigue (result of anaemia, shortage of red blood cells), recurrent minor infections or poor healing of minor cuts (due to inadequate supply of normal immune cells). Acute myeloid leukaemia is life-threatening, in particular due to high mortality for patients who do not achieve an initial complete remission.

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

At the time of designation affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 46,000 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 459,700,000 (Eurostat 2004).

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, the symptoms, and the general health of the patient. The primary treatment of acute myeloid 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.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' might be of potential significant benefit for the treatment of acute myeloid leukaemia, mainly because it may be used in combination with other treatments and it may 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?

An antisense oligonucleotide is a fragment of modified DNA (the genetic material), designed to be stable and bind to a specific gene to inhibit its expression (decrease the production of the protein that the gene regulates). Antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' binds to a gene that regulates a protein called p53. This protein is very important for the cells’ natural ability to repair themselves from damage. According to the sponsor, antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' will by decreasing the production of p53 in tumour cells thus make them more susceptible to be destroyed by the damage that chemotherapy drugs causes.

What is the stage of development of this medicine?

The effects of antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with acute myeloid leukaemia were ongoing.

Antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' was not authorised anywhere worldwide for the treatment of acute myeloid leukaemia, at the time of submission. Orphan designation of antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' was granted in the United States for acute myelogenous leukaemia.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 4 October 2006 a positive opinion recommending the grant of the above-mentioned 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>Antisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' (see comments box for cenersen sodium)</p>
Active substanceAntisense oligonucleotide 5'-d[P-Thio] (CCCTG CTCCC CCCTG GCTCC)-3' (see comments box for cenersen sodium)
Medicine Name
Disease/conditionTreatment of acute myeloid leukaemia
Date of decision02/11/2006
OutcomePositive
Orphan decision numberEU/3/06/416

Review of designation

Sponsor’s contact details:

EleosInc Limited
Attention: Dayton Reardan
21 Wilson Street
London EC2M 2TD
United Kingdom
Telephone: +44 20 78 26 45 04
Telefax: +44 20 75 88 05 55
E-mail: Dreardan@EleosInc.com

Patients’ associations contact points:

Leukaemia CARE
One Birch Court
Blackpole East
Worcester
Worcestershire WR3 8SG
Telephone: +44 1905 755977 / +44 845 521 3456
24 hour CARE line 0800 169 6680 (UK residents only)
Telefax: +44 1905 755166
E-mail: info@leukaemiacare.org.uk

Ligue Nationale contre le Cancer
12, rue Corvisart
75013 Paris
France
Telephone : +33 1 53 55 24 00
Telefax : +33 1 43 36 91 10
E-mail: ligue@ligue-cancer.net

Deutsche Krebshilfe e.V.
Buschstrasse 32
53113 Bonn
Postfach 1467
53004 Bonn
Germany
Telephone: +49 2 28 72 99 00
Telefax: +49 22 87 29 90 11
E-mail: deutsche@krebshilfe.de