EU/3/11/872: Orphan designation for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma is a primary cancer of the liver (a cancer that starts in the liver, rather than a cancer that has spread to the liver from another location in the body). It is more common in men than in women, and occurs mostly in people who have scarring of the liver (cirrhosis) or following infection with the hepatitis-B or -C viruses. Symptoms of the disease include pain and swelling in the abdomen, weight loss, weakness, loss of appetite and nausea (feeling sick).

Hepatocellular carcinoma is a severe and life-threatening disease that is associated with shortened life expectancy.

At the time of designation, hepatocellular carcinoma affected approximately 2 in 10,000 people in the European Union (EU). This is equivalent to a total of around 102,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

At the time of designation, several medicines were authorised in the EU for the treatment of hepatocellular carcinoma. The choice of treatment depended mainly on how advanced the disease was. The only therapies to cure the cancer were surgery to remove the tumour and liver transplantation, but these could only be carried out in very few patients. Other treatments included chemotherapy (medicines to treat cancer) and immunotherapy (medicines that stimulate the immune system to kill the cancer cells). Radiofrequency ablation (using a probe placed into the tumour to heat and destroy cancer cells) and ethanol injection were also used to remove small tumours.

The sponsor has provided sufficient information to show that sulfonated monophosphorylated mannose oligosaccharide might be of significant benefit for patients with hepatocellular carcinoma because this medicine works in a different way to existing treatments and early studies show that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Sulfonated monophosphorylated mannose oligosaccharide is expected to work by blocking an enzyme called heparanase, which is present in large amounts in cancer cells, including hepatocellular-carcinoma cells. Heparanase helps the cancer cells to grow and invade surrounding tissues through its involvement in breaking down cell membranes and in activating 'growth factors' that help form blood vessels. By blocking the enzyme, this medicine is expected to help slow the growth of the cancer and prevent it from spreading.

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with this medicine in patients with hepatocellular carcinoma were ongoing.

At the time of submission, sulfonated monophosphorylated mannose oligosaccharide was not authorised anywhere in the EU for hepatocellular carcinoma or designated as an 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 9 March 2011 recommending the granting of this designation.

• 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.