Kalbitor: Withdrawal of the marketing authorisation application

Kalbitor is a medicine that contains the active substance ecallantide. It was to be available as a solution for injection.

Kalbitor was expected to be used to treat symptoms of attacks of hereditary angioedema. Patients with hereditary angioedema have attacks of swelling that can occur anywhere in the body, such as in the face, limbs, gut and throat, causing discomfort and pain and sometimes in the case of throat attacks difficulty in breathing.

Kalbitor was designated an 'orphan medicine' (a medicine to be used in rare diseases) on 18 December 2002 for the treatment of angioedema.

The active substance in Kalbitor, ecallantide, blocks an enzyme in the blood called 'kallikrein'.

Kallikrein is part of a complex network of proteins (known as the kallikrein-kinin system) that has several effects in the body, one of which results in increased levels of a protein called bradykinin that causes the blood vessels to widen and leak fluid into the surrounding tissue. This leakage of fluids causes the swelling attacks seen in angioedema. By blocking the actions of kallikrein, Kalbitor is expected to help reduce the swelling and related symptoms of angioedema.

The ecallantide in Kalbitor is produced by a method known as 'recombinant DNA technology'. This means that it is made by a cell that has received a gene (DNA), which makes the cell able to produce it.

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

The company presented the results of two main studies in patients aged 10 years and above who had hereditary angioedema. There were 72 patients in one study and 96 in the other. The patients were treated with either Kalbitor or placebo (a dummy treatment) within 8 hours of having an attack. Those judged to be at risk of blockage of the airway were given additional treatments if required.

The main measure of effectiveness was based on the improvement in patients' symptoms after four hours. Other measures included the time that it took for the attack to resolve.

The application was withdrawn after 'day 181'. This means that the CHMP had evaluated the documentation provided by the company and formulated lists of questions. After the CHMP had assessed the company's responses to the last round of questions in an oral explanation, there were still some unresolved issues.

Based on the review of the data and the company's response to the CHMP lists of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Kalbitor could not have been approved.

The CHMP had concerns about hypersensitivity reactions, which were seen at a higher rate in patients treated with Kalbitor. Hypersensitivity reactions occur when the body's immune system reacts against a medicine, and include reactions commonly known as allergic reactions. The CHMP also had concerns related to the effectiveness of the proposed doses in heavier patients.

Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Kalbitor did not outweigh its risks.

The letter from the company notifying the Agency of the withdrawal of the application is available.
Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Kalbitor did not outweigh its risks.

The company has informed the CHMP that the withdrawal will not have any consequences for patients enrolled in any trials.