EU/3/10/846 : Orphan designation for the treatment of oesophagus carcinoma

Oesophagus carcinoma is cancer of the oesophagus (the tube that connects the mouth to the stomach). It usually starts in the cells lining the oesophagus, and spreads easily to other parts of the body. Oesophagus carcinoma is often detected late because in the early stage of the disease patients do not have significant symptoms. The cancer is usually diagnosed in people aged over 60 years, and men are about twice as likely to develop the disease as women.

Oesophagus carcinoma is a life-threatening disease because of its serious complications such as dysphagia (difficulty swallowing) that lead to poor overall survival.

At the time of designation, oesophagus carcinoma affected approximately 0.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 25,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

The choice of treatment for oesophagus carcinoma depends on where in the oesophagus the cancer is located, and how advanced it is. At the time of orphan designation, the main treatment was surgery, sometimes preceded by radiotherapy (treatment with radiation) or chemotherapy (medicines to treat cancer) to make the cancer shrink and easier to remove. Other medicines were also used after surgery to treat complications.

The sponsor has provided sufficient information to show that paclitaxel (aqueous gel) might be of significant benefit for patients with oesophagus carcinoma because the medicine is expected to be given locally, causing fewer side effects than systemic treatments, such as standard chemotherapy, which reach cells throughout the body. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Paclitaxel has been available as an anticancer medicine since 1993. It belongs to the group of anticancer medicines known as the 'taxanes'. Paclitaxel blocks the ability of cancer cells to break down their internal 'skeleton' that allows them to divide and multiply. With their skeleton still in place, the cells cannot divide and they eventually die.

Paclitaxel (aqueous gel) is a depot formulation of paclitaxel that is expected to be given by injection directly into the tumour. This is a type of formulation where the medicine is prepared so that it is slowly released. The paclitaxel is expected to mainly remain within the tumour without spreading throughout the body, thereby causing fewer side effects.

The effects of paclitaxel (aqueous gel) have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients with oesophagus carcinoma was ongoing.

At the time of submission, paclitaxel (aqueous gel) was not authorised anywhere in the EU for oesophagus carcinoma. Orphan designation of paclitaxel (aqueous gel) had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 December 2010 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.