EU/3/16/1632: Orphan designation for the diagnosis of 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 liver scarring (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.

Hepatocellular carcinoma is debilitating in the long term and life-threatening, with patients surviving on average for around 6 to 20 months after diagnosis.

At the time of designation, the number of patients eligible for diagnosis of hepatocellular carcinoma was estimated to be approximately 2 people in 10,000 in the European Union (EU). This was equivalent to a total of around 103,000 people*, and is below the ceiling for orphan designation. 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 eligible for diagnosis of 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 513,700,000 (Eurostat 2016).

At the time of designation, several methods were used for the diagnosis of hepatocellular carcinoma, including histopathology (examining a tissue under the microscope) and biochemical testing (measuring substances produced by tumours), as well as imaging methods such as magnetic resonance imaging (MRI) and computer tomography (CT) using so-called contrast agents to obtain better images of organs and tissues.

The sponsor has provided sufficient information to show that florilglutamic acid (¹⁸F) might be of significant benefit for patients with hepatocellular carcinoma, with preliminary data showing it could improve the detection of small cancer lesions that are currently missed when using authorised contrast agents in MRI scans. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Florilglutamic acid (¹⁸F) is a radioactive compound for use with an imaging method known as positron emission tomography (PET). Florilglutamic acid (¹⁸F) enters cells through a transport system known as x_C- which is more abundant in cancer tissue. When injected into the patient, florilglutamic acid (¹⁸F) is more effectively taken up by the cancer cells in the liver from where it is expected to emit radiation that can be detected in a PET scan, thereby allowing the cancer to be diagnosed.

The effects of florilglutamic acid (¹⁸F) have been evaluated in experimental models.

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

At the time of submission, the medicine was not authorised anywhere in the EU for diagnosing hepatocellular carcinoma or designated as an orphan medicinal product elsewhere for this indication.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 February 2016 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.