EU/3/10/827

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Orphan designation

On 17 December 2010, orphan designation (EU/3/10/827) was granted by the European Commission to HungaroTrial Ltd, Hungary, for recombinant human lysosomal acid lipase for the treatment of lysosomal acid lipase deficiency.

The sponsorship was transferred to Synageva BioPharma Ltd, United Kingdom, in August 2011.

The sponsorship was transferred to Alexion Europe SAS, France, in October 2015.

Update: recombinant human lysosomal acid lipase, sebelipase alfa (Kanuma) has been authorised in the EU since 28 August 2015 for long-term enzyme replacement therapy (ERT) in patients of all ages with lysosomal acid lipase (LAL) deficiency.

What is lysosomal acid lipase deficiency?

Lysosomal acid lipase deficiency is an inherited disease caused by the lack of one of the enzymes needed to break down fats within cells. In the absence of this enzyme, called lysosomal acid lipase, fats accumulate in the body’s cells and tissues, causing symptoms such as growth failure, enlarged liver, diarrhoea and malabsorption (when nutrients from food are not easily absorbed during digestion).

Lysosomal acid lipase deficiency is a severe and life-threatening disease which, in its most severe form, is usually fatal in the first year of life.

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

At the time of designation, lysosomal acid lipase deficiency affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This isbased 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 506,300,000 (Eurostat 2010).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of lysosomal acid lipase deficiency. Patients were advised to follow a diet low in fats. In some cases, haematopoietic (blood) stem cell transplantation had been used, but with modest results. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

How is this medicine expected to work?

Recombinant human lysosomal acid lipase is an ‘enzyme replacement therapy’ that is expected to work by replacing the missing enzyme in lysosomal acid lipase deficiency, helping to break down fats and stopping them building up in the body’s cells.

Recombinant human lysosomal acid lipase is produced by a method known as ‘recombinant DNA technology’: it is extracted from the eggs of hens that have been given genes that make them able to produce an exact copy of the human enzyme in their eggs.

What is the stage of development of this medicine?

The effects of recombinant human lysosomal acid lipase have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with lysosomal acid lipase deficiency had been started.

At the time of submission, recombinant human lysosomal acid lipase was not authorised anywhere in the EU for the treatment of lysosomal acid lipase deficiency. Orphan designation of the medicine 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 7 October 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 quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Product details for <p>Recombinant human lysosomal acid lipase</p>
Active substanceRecombinant human lysosomal acid lipase
Medicine NameKanuma
Disease/conditionTreatment of lysosomal acid lipase deficiency
Date of decision17/12/2010
OutcomePositive
Orphan decision numberEU/3/10/827

Review of designation

During its meeting of 14 to 16 July 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/827 for Kanuma (sebelipase alfa, previously known as recombinant human lysosomal acid lipase) as an orphan medicinal product for the treatment of lysosomal acid lipase deficiency. 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 and prevalence of the condition, and the existence of other methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained1.


1The 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 Kanuma for:

‘long-term enzyme replacement therapy in patients of all ages with lysosomal acid lipase deficiency’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of lysosomal acid lipase deficiency’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Lysosomal acid lipase deficiency remains a severe disease which, in its most severe form, is usually fatal in the first year of life.

Prevalence of the condition

The sponsor provided updated information on the prevalence of lysosomal acid lipase deficiency based on data from the scientific literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of lysosomal acid lipase deficiency 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 still estimated to be not more than 0.2 people in 10,000. This is equivalent to a total of not more than 10,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for patients affected by this condition. Patients were advised to follow a diet low in fats. In some cases, haematopoietic (blood) stem cell transplantation had been used, but with modest results. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

Conclusions

Kanuma still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Alexion Europe SAS
1-15, avenue Edouard Belin
92500 Rueil-Malmaison
France
Tel. +33 1473 23621
Fax +33 1471 02446
E-mail: medicalinformation.europe@alxn.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.