Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in July 2008 on request of the sponsor.
On 10 March 2005, orphan designation (EU/3/05/268) was granted by the European Commission to Pfizer Limited, United Kingdom, for (Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate for the treatment of renal cell carcinoma.
(Z)-N-[2-(diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate has been authorised in the EU as Sutent since 19 July 2006 for the treatment of advanced and/or metastatic renal cell carcinoma (MRCC) after failure of interferon alfa or interleukin-2 therapy.
Renal cell carcinoma (also called cancer of the kidney or renal adenocarcinoma) is a disease in which cancer (malignant) cells are found in certain tissues of the kidney. Inside each kidney are tiny tubules that filter and clean the blood, taking out waste products, and making urine. Renal cell carcinoma is a cancer of the lining of the tubules in the kidney. Renal cell carcinoma accounts for approximately 85% of all kidney cancers. Signs of cancer are difficult to detect in early stages of the disease, and about half of the patients are diagnosed when the disease has spread around the kidney or to distant parts of the body. Surgery is a common treatment of renal cell cancer, and allows taking out the cancer in an operation, although the cancer may appear again. Renal cell carcinoma is life-threatening.
At the time of designation, renal cell carcinoma affected approximately 3.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 161,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).
There are treatments for most patients with renal cell cancer. These may include surgery (taking out the cancer in an operation), chemotherapy (using drugs to kill cancer cells), radiation therapy (using high-dose x-rays or other high-energy rays to kill cancer cells), hormone therapy (using hormones to stop cancer cells from growing), and biological therapy (using the body's immune system to fight cancer). The primary therapies for advanced renal cancer are biologic agents, such as interleukin-2 (IL-2) and interferon-? (IFN-?). Other anticancer agents had also been authorised in the Community for treatment of renal cell carcinoma at the time of submission of the application for orphan designation.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that Z)-N-[2-(Diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate might be of potential significant benefit for the treatment of renal cell carcinoma mainly because it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain orphan status.
Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. Z)-N-[2-(Diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate blocks (inhibits) the enzyme tyrosine kinase. This enzyme plays a role in a cascade of molecular reactions to bring a certain signal from outside the cell into the cell thereby controlling the growth of the cells. In cancer cells, the function of this enzyme is disturbed causing uncontrolled growth and multiplication of the cancer cells.
Z)-N-[2-(Diethylamino)ethyl]-5-[(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (S)-2-hydroxysyccinate might, by inhibition of this enzyme activity, help in slowing down or stopping the further growth of the cancer cells.
At the time of submission of the application for orphan designation, clinical trials in patients with renal cell carcinoma were ongoing.
The medicinal product was not authorised anywhere worldwide for renal cell carcinoma or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 3 February 2005 a positive opinion recommending the grant of the above-mentioned 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.
Pfizer Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ
United Kingdom
Tel. +44 (0)1304 616 161
Fax +44 (0)1304 652 144
E-mail: orphan_enquiries@pfizer.com
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: