EU/3/08/603

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Orphan designation

On 19 January 2009, orphan designation (EU/3/08/603) was granted by the European Commission to European Medical Advisory Services Limited, United Kingdom, for pralatrexate for the treatment of non-papillary transitional cell carcinoma of the urinary bladder.

The sponsorship was transferred to Allos Therapeutics Limited, United Kingdom, in February 2010.

What is non-papillary transitional cell carcinoma of the urinary bladder?

A carcinoma is any cancer that arises from epithelial cells. These cells line cavities and structures throughout the body, such as the bladder. Transitional epithelial cells surround organs that can stretch. For example, the urothelium is the cell layer that lines the bladder and ureter in the human body. Non-papillary transitional cell carcinoma is a carcinoma of this type of cells that line the urinary bladder. This cancer is also called urothelial carcinoma and it accounts for more than 90% of all bladder cancers.

There are two distinct transitional cell carcinomas of the urinary bladder called papillary and non-papillary depending on their aspect (raised or flat). While papillary carcinomas do not invade tissues around or disseminate through the body (metastasize), non-papillary carcinomas can aggressively invade the bladder wall (they are usually invasive at the time of diagnosis) and often disseminate quickly during the course of the disease. Non-papillary transitional cell carcinoma of the urinary bladder is a life-threatening condition.

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

At the time of designation non-papillary transitional cell carcinoma of the urinary bladder affected approximately 3.7 in 10,000 people in the European Union (EU) *. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 186,000 people.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).

What treatments are available?

The choice of treatment for non-papillary cell carcinoma of the urinary bladder depends on the extent of the disease. Treatment for the condition includes surgery to remove the cancer (transurethral resection), immunotherapy, interferon therapy, radiation therapy, and chemotherapy (using drugs to kill cancer cells).
Pralatrexate might be of potential significant benefit for the treatment of non-papillary transitional cell carcinoma of the urinary bladder because it is expected to improve the overall outcome of patients with the condition particularly due to its expected activity against the cancer cells. 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?

Enzymes are proteins produced by the cells of the body that speed up (catalyse) the conversion of certain substances into others. Pralatrexate inhibits (blocks) the activity of the enzyme dihydrofolate reductase, which is necessary for cell growth and multiplication. As the function of dihydrofolate reductase is inhibited, cell growth can be arrested. Since non-papillary transitional cell carcinoma of the urinary bladder is caused by the uncontrolled growth of the bladder transitional epithelial cells, pralatrexate might help in slowing down or stopping this uncontrolled cell growth.

What is the stage of development of this medicine?

The effects of pralatrexate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial in patients with non-papillary transitional cell carcinoma of the urinary bladder was ongoing.

At the time of submission, pralatrexate was not authorised anywhere in the world for non-papillary transitional cell carcinoma of the urinary bladder or designated as 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 5 November 2008 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;
  • and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Product details for <p>Pralatrexate</p>
Active substancePralatrexate
Medicine Name
Disease/conditionTreatment of non-papillary transitional cell carcinoma of the urinary bladder
Date of decision18/01/2009
OutcomePositive
Orphan decision numberEU/3/08/603

Review of designation

Sponsor's contact details:

Allos Therapeutics Limited
71 Knowl Piece
Wilbury Way
Hitchin
Hertfordshire SG4 OTY
United Kingdom
Telephone: +44 1462 424 416
Telefax: +44 1462 600 453

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.