EU/3/04/194

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Orphan designation

On 8 March 2004, orphan designation (EU/3/04/194) was granted by the European Commission to Mr Aart Brouwer, the Netherlands, for adeno-associated viral vector expressing lipoprotein lipase for the treatment of lipoprotein-lipase deficiency.

The sponsorship was transferred to Amsterdam Molecular Therapeutics, the Netherlands, in December 2006. 

In July 2012, Amsterdam Molecular Therapeutics changed name to uniQure biopharma B.V.

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

What is lipoprotein-lipase deficiency?

Triglycerides are one of the basic chemical ‘building blocks’ from which fats are formed. Lipoprotein lipase (LPL) is the key enzyme in the use and transformation of triglyceride-rich lipoproteins and protects the human body against the excessive rise of triglycerides after every meal. LPL is produced by skeletal muscle cells and excreted into the circulation where it awaits the triglycerides for breakdown.

LPL deficiency is an inherited condition that results in extremely high concentrations of circulating triglyceride-rich lipoproteins. LPL deficiency usually presents itself at infancy or childhood. It is chronically debilitating with typical complaints of severe abdominal pain, repetitive colicky pains, repeated episodes of pancreatitis (inflammation of the pancreas) and often ‘failure to thrive’.

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

At the time of designation, lipoprotein lipase deficiency affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 930 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

What treatments are available?

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition. Treatment of patients with LPL deficiency primarily involved restriction of dietary fat to less than 20% of total calories. The dietary regimen was difficult for patients to adhere to and there was, therefore, often recurrent pancreatitis in these patients.

How is this medicine expected to work?

Adeno-associated viral vector expressing LPL is a medicinal product that uses a virus to carry the gene necessary for the production of the enzyme LPL. A virus is a small organism capable of introducing genetic material in cells. The type of virus (adeno-associated virus) used in this medicinal product is modified so as not to cause any disease in humans.

What is the stage of development of this medicine?

The evaluation of the effects of adeno-associated viral vector expressing LPL in experimental models is on-going. At the time of submission of the application for orphan designation, no clinical trials in patients with LPL deficiency had been initiated.

Adeno-associated viral vector expressing LPL was not marketed anywhere worldwide for LPL deficiency or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 February 2004 recommending the granting of this designation.

Update: Glybera (alipogene tiparvovec) was authorised in the EU on 25 October 2012. Glybera is indicated for adult patients diagnosed with familial LPL deficiency and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. The diagnosis of LPL deficiency has to be confirmed by genetic testing. The indication is restricted to patients with detectable levels of LPL protein.

More information on Glybera 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>Adeno-associated viral vector expressing lipoprotein lipase</p>
Active substanceAdeno-associated viral vector expressing lipoprotein lipase
Medicine NameGlybera
Disease/conditionTreatment of lipoprotein-lipase deficiency
Date of decision08/03/2004
OutcomePositive
Orphan decision numberEU/3/04/194

Review of designation

During its meeting of 4-5 September 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/04/194 for Glybera (alipogene tiparvovec, previously known as adeno-associated viral vector expressing lipoprotein lipase) as an orphan medicinal product for the treatment of lipoprotein-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 satisfactory 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 European Union (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 Glybera for:

‘adult patients diagnosed with familial lipoprotein-lipase deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. The diagnosis of LPLD has to be confirmed by genetic testing. The indication is restricted to patients with detectable levels of lipoprotein lipase protein.'

This falls within the scope of the product’s designated orphan indication, which is ‘treatment of LPLD’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2004. LPLD remains a condition that is debilitating in the long term and life-threatening, particularly due to repeated attacks of pancreatitis.

Prevalence of the condition

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of LPLD 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 approximately 0.02 people in 10,000. This is equivalent to a total of around 1,000 people in the EU.

Existence of other satisfactory methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no satisfactory methods of treatment were authorised in the EU for patients affected by this condition.

Conclusions

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

Sponsor’s contact details

uniQure biopharma B.V.
Meibergdreef 61
1105 BA Amsterdam
The Netherlands
Tel. +31 20 566 7394
Fax +31 20 566 9272
E-mail: info@uniqure.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.