EU/3/13/1202

On 13 November 2013, orphan designation (EU/3/13/1202) was granted by the European Commission to Daiichi Sankyo Development Ltd, United Kingdom, for tivantinib for the treatment of hepatocellular carcinoma.

What is hepatocellular carcinoma?

Hepatocellular carcinoma is a primary cancer of the liver (a cancer that starts in the liver, rather than one that has spread to the liver from elsewhere 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 after 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 serious and life-threatening illness that is associated with poor overall survival.

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 was equivalent to a total of around 51,000 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).

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*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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, some patients with early stage hepatocellular carcinoma were treated with surgery to remove part of the liver. Chemotherapy (medicines to treat cancer) was generally used after surgery or on its own if surgery was not possible or the disease had spread to other parts of the body (metastatic disease). Sorafenib was authorised in the EU for use in hepatocellular carcinoma.

The sponsor has provided sufficient information to show that tivantinib might be of significant benefit for patients with hepatocellular carcinoma because early studies show that it may delay the progression of the disease in patients whose disease has stopped responding to, or is resistant to, sorafenib. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Tivantinib works by blocking the action of an enzyme known as c-MET kinase. C-MET kinase is found in high amounts in some cancer cells and is involved in the growth and spread of cancer cells and in the development of new blood vessels to supply them. By blocking this enzyme, the medicine is expected to stop the cancer cells from dividing, and thereby slow down the progression of the disease.

What is the stage of development of this medicine?

The effects of tivantinib have been evaluated in experimental models.

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

At the time of submission, tivantinib 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 October 2013 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.