EU/3/18/2028:

Angioedema is a disease characterised by attacks of swelling beneath the skin that can occur anywhere in the body, such as in the face, limbs, gut and larynx (voice box), causing discomfort and pain.

Angioedema can be caused by low levels of 'C1 inhibitor', a protein in the blood involved in the control of the 'kallikrein-kinin' system. This system plays a role in causing the swelling and inflammation seen in angioedema. Patients with low levels of C1 inhibitor have excessive activity of this system, which leads to the symptoms of angioedema.

The C1 inhibitor deficiency can be 'hereditary' or 'acquired'. Hereditary angioedema is caused by abnormalities in the gene responsible for the production of C1 inhibitor. Acquired angioedema is caused by conditions that increase the breakdown of C1 inhibitor such as in some cancers and autoimmune diseases.

Hereditary angioedema is a long-term debilitating disease that may be life threatening because, when the swelling occurs in the larynx, it can obstruct the airways and impede breathing.

At the time of designation, hereditary angioedema affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 26,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).

At the time of designation, several medicines were authorised in the EU for the treatment of hereditary angioedema. These included medicines containing human C1 inhibitors (Cinryze and Berinert), conestat alfa (Ruconest) and icatibant (Firazyr).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with hereditary angioedema. This is because early studies showed that it could help to prevent swelling attacks. In addition, the medicine is to be given by mouth, and thus is expected to be easier to use than currently available treatment given by injection.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine works by blocking the activity of kallikrein proteins, which are part of the kallikrein-kinin system. As the system is overactive in patients with angioedema, resulting in the characteristic swelling and inflammation, blocking it is expected to reduce the number of angioedema attacks.

The effects of the 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 hereditary angioedema were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for hereditary angioedema. Orphan designation of the medicine had been granted in the United States for treatment of C1-inhibitor-dependent angioedema.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 May 2018 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.