EU/3/17/1897 - orphan designation for treatment of hepatocellular carcinoma
tirapazamine
OrphanHuman
Overview
On 17 July 2017, orphan designation (EU/3/17/1897) was granted by the European Commission to PhaRA bvba, Belgium, for tirapazamine for the treatment 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 hepatitis B or C infection. Features of the disease include yellow skin, pain and swelling in the abdomen, easy bruising, weight loss, weakness, loss of appetite and nausea.
Hepatocellular carcinoma is long-term debilitating and life threatening, with patients surviving on average for a few months or years after diagnosis.
At the time of designation, hepatocellular carcinoma affected approximately 1.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 77,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 515,700,000 (Eurostat 2017).
At the time of designation, some patients with early stage hepatocellular carcinoma were treated with surgery to remove part of the liver, liver transplantation or radiofrequency ablation (directing heat and electricity through a needle to destroy cancer cells). Chemotherapy (medicines to treat cancer) was used if surgery was not possible or the disease had spread to other parts of the body (metastatic disease). Nexavar (sorafenib) was authorised in the EU for use in hepatocellular carcinoma.
The sponsor has provided sufficient information to show that tirapazamine might be of significant benefit for patients with hepatocellular carcinoma, with early studies indicating that it can improve treatment outcomes when compared with current treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Tirapazamine damages the DNA strands in cells, which stops the cells from multiplying. However, the medicine only works in an environment with little or no oxygen. In order for the medicine to work against liver cancer cells, patients will undergo a surgical procedure known as transarterial embolisation, which blocks off part of the tumour's blood supply, creating a low-oxygen environment. Tirapazamine is to be injected first into the patient followed by embolisation. In this way, the medicine is expected to damage the DNA of cancer cells and help slow down the progression of the disease.
The effects of tirapazamine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with tirapazamine in patients with hepatocellular carcinoma were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for hepatocellular carcinoma. Orphan designation had been granted in the United States for the condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 June 2017 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.
Key facts
- Active substance
- tirapazamine
- Intended use
- Treatment of hepatocellular carcinoma
- Orphan designation status
- Positive
- EU designation number
- EU/3/17/1897
- Date of designation
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: