This medicine is now known as etoposide toniribate.
On 4 June 2014, orphan designation (EU/3/14/1270) was granted by the European Commission to CellAct Pharma GmbH, Germany, for (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-Ethylidene]-β-D-glucopyranosyl]-oxy]-5-(4-({[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]carbonyl}oxy)-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one for the treatment of biliary tract cancer.
The sponsorship was transferred to Mundipharma Corporation (Ireland) Limited, Ireland in April 2019.
The sponsorship was transferred to CellAct Pharma GmbH, Germany in April 2022.
Biliary tract cancer is cancer of the bile ducts and gallbladder. These are parts of the digestive system that transport and store bile, a fluid which is produced by the liver and released into the intestines after a meal to help digest fats. The cancer is characterised by various clinical features such as abnormal liver function tests, pain in the belly, yellowish discoloration of the skin, and weight loss.
Biliary tract cancer is a long-term debilitating and life-threatening disease which is often diagnosed when the disease has reached a late stage, worsening the prognosis for the patient.
At the time of designation, biliary tract cancer affected approximately 1.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 87,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 511,100,000 (Eurostat 2014).
At the time of designation, choice of treatment for biliary tract cancer depended mainly on how advanced the disease was. Some patients with early disease could undergo surgery to remove the cancer. Other treatments included chemotherapy (medicines to treat cancer).
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with biliary tract cancer because early studies suggest that it might improve the outcome of patients who did not respond to standard treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
This medicine is a 'prodrug' of a substance called etoposide, which has been authorised in the EU for many years to treat cancer. It consists of etoposide linked to another substance called an ester group. The medicine is broken down in the body by enzymes called carboxylesterases, releasing the active etoposide. Because these enzymes are present in high levels in the digestive system, including the biliary tract, high levels of etoposide are expected to be produced within the cancerous tissue, where they damage the DNA of cancer cells, killing them and reducing the growth of the cancer.
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 the medicine in patients with biliary tract cancer were ongoing.
At the time of submission, this medicine was not authorised anywhere in the EU for biliary tract cancer 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 April 2014 recommending the granting of this designation.
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.
CellAct Pharma GmbH
Otto-Hahn-Strasse 15
Eichlinghofen
44227 Dortmund
Germany
E-mail: info@cellact.eu
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: