EU/3/07/482 - orphan designation for treatment of hepatocellular carcinoma

sulfonated monophosphorylated mannose oligosaccharide

Overview

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in December 2008 on request of the Sponsor.

On 14 September 2007, orphan designation (EU/3/07/482) was granted by the European Commission to Constella Group Ltd, United Kingdom, for sulfonated monophosphorylated mannose oligosaccharide for the treatment of hepatocellular carcinoma.

What is hepatocellular carcinoma?

Tumours that begin in the liver are known as primary liver tumours. The most frequent type of primary liver tumour that has the potential to infiltrate healthy tissues (malignant) is called hepatocellular carcinoma. The most common factors known to be associated with this disease are the viral infections causing liver inflammations (hepatitis B and hepatitis C) and subsequently cirrhosis, or alcohol-induced liver cirrhosis. Hepatocellular carcinoma is a life-threatening condition.

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

At the time of designation, hepatocellular carcinoma affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 50,000 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 498,000,000 (Eurostat 2006).

What treatments are available?

The choice of the treatment of hepatocellular carcinoma depends on several factors, mainly the stage of the disease. Treatments may include surgery, radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells), chemotherapy (using drugs to kill cancer cells) or immunotherapy (treatment by stimulation of the body's own defense system). At the time of submission of the application for orphan drug designation, several products were authorised for the condition in some Member States of the Community. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that sulfonated monophosphorylated mannose oligosaccharide might be of potential significant benefit for the treatment of hepatocellular carcinoma, because of its new mechanism of action and the possibility to use it in combination with current treatments. 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?

Sulfonated monophosphorylated mannose oligosaccharide is structurally similar to the naturally occurring compound called heparan sulphate, which is present in the extracellular matrix (the mix of molecules between cells in tissues). For tumours to be able to grow and invade into surrounding tissues, the tumour cells have to be able to degrade heparan sulphate, and for that purpose tumour cells overexpress an enzyme called heparanase in their cell membrane.

The sponsor has suggested that the product acts by binding to this enzyme and thus inhibiting the tumour from degrading heparan sulphate and growing into to the surrounding tissues. Heparan sulphate normally also interacts with a molecule called VEGF (vascular endothelial growth factor) which stimulates the formation of blood vessels. Also, the sponsor has suggested that sulfonated monophosphorylated mannose oligosaccharide binds to VEGF and inhibits the ability of the tumour to form new blood vessels, which is critical for the survival of tumour cells.

What is the stage of development of this medicine?

The effects of sulfonated monophosphorylated mannose oligosaccharide were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with sulfonated monophosphorylated mannose oligosaccharide were ongoing.

Sulfonated monophosphorylated mannose oligosaccharide was not authorised anywhere worldwide for the treatment of hepatocellular carcinoma, nor designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 25 July 2007 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.

EU/3/07/482: Public summary of positive opinion for orphan designation of sulfonated monophosphorylated mannose oligosaccharide for the treatment of hepatocellular carcinoma

Adopted Reference Number: EMEA/COMP/135044/2008 Rev.1

Key facts

• Active substance:
  sulfonated monophosphorylated mannose oligosaccharide
• Intended use:
  Treatment of hepatocellular carcinoma
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/07/482
• Date of designation:
  14/09/2007
• Sponsor:

  Constella Group Ltd; 20 Milton Park; Abingdon; Oxfordshire; OX14 4SH; United Kingdom; Telephone: + 44 1235 437 400; Telefax: + 44 1235 437 437; E-mail: www.constellagroup.com (follow link to “Contact Us”)