Removab - catumaxomab

What is Removab?

Removab is a concentrate for the preparation of a solution for infusion (drip). The active ingredient contained in it is catumaxomab.

What is Removab used for?

Removab is used to treat malignant ascites, an accumulation of fluid in the peritoneal cavity (space in the abdomen) caused by cancer. The medicine is used in case of unavailability of standard treatment or if the standard treatment is no longer viable.

Removab can only be used in patients with EpCAM-positive carcinomas, ie for those tumors characterized by a massive presence of a molecule called EpCAM on the surface of tumor cells.

The medicine can only be obtained with a prescription.

How is Removab used?

Treatment with Removab should only be given under the supervision of a doctor experienced in the use of anticancer medicines.

Removab is administered by intraperitoneal infusion (ie in the peritoneal cavity) via a pump system, usually with four infusions at increasing doses of 10 to 150 micrograms over 11 days. At least two days must elapse between one infusion and another, but the interval may be prolonged in the event of side effects. The overall duration of the treatment must not exceed 20 days.

Patients should be monitored after each infusion. Removab should not be given at once or by different routes. Before treatment, it is recommended that the patient be given medication against pain, fever and inflammation. Patients with severe liver problems or moderate or severe kidney problems should be treated with Removab only after careful consideration of the risks and benefits of the medicine. The use of Removab is not recommended in young people under 18 years of age due to the lack of information on safety and efficacy for this age group.

How does Removab work?

In cancer patients, ascites is formed because the cancer cells develop on the peritoneum, the membrane around the peritoneal cavity, blocking the natural drainage of fluids from the abdomen.

The active substance in Removab, catumaxomab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) made to recognize a specific structure (called an antigen) present on some cells of the body and bind to it. Catumaxomab was designed to bind to two antigens: EpCAM, present at high levels on some types of tumor cells, and CD3, present in T cells. T cells are part of the immune system (the natural defenses of 'organism) and are involved in coordinating the death of infected and abnormal cells. By binding to these two antigens, the catumaxomab forms a bridge between the cancer cells and the T cells, which brings the cells together so that the T cells can neutralize the cancer cells. Catumaxomab also binds to a third substance, called the Fc-gamma receptor, which helps the body's immune system to concentrate on cancer cells.

How has Removab been studied?

The effects of Removab were first tested in experimental models before being studied in humans.

Removab was the subject of one main study involving 258 patients with malignant ascites caused by EpCAM-positive cancer and for whom standard therapy was not available or no longer viable. In this study, Removab, used in combination with the drainage of fluid from the abdomen, was compared with the use of drainage alone. The main efficacy parameter was patient survival time without the need for further drainage.

What benefit has Removab shown during the studies?

The association of Removab and drainage was found to be more effective than just drainage in the treatment of malignant ascites. On average, patients treated with Removab could live for 46 days without the need for further drainage compared to 11 days for patients treated with drainage alone.

What is the risk associated with Removab?

90% of patients treated with Removab had side effects. The most common side effects associated with Removab (seen in more than 1 patient in 10) are lymphopenia (low level of lymphocytes, a type of white blood cell), abdominal pain, nausea, vomiting, diarrhea, pyrexia (fever), fatigue, chills and pains. For the full list of all side effects reported with Removab, see the Package Leaflet.

Removab should not be used in patients who may be hypersensitive (allergic) to catumaxomab, mouse or rat proteins or any of the other components.

Why has Removab been approved?

The Committee for Medicinal Products for Human Use (CHMP) has decided that Removab's benefits outweigh

its risks in the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive carcinoma for which standard therapy is not available or no longer viable. The committee recommended that Removab be given marketing authorization.