EU/3/15/1551 - orphan designation for treatment of hereditary angioedema

Recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein (lanadelumab)

Overview

On 9 October 2015, orphan designation (EU/3/15/1551) was granted by the European Commission to Dyax Ltd, United Kingdom, for recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein for the treatment of hereditary angioedema.

This medicine is now known as lanadelumab.

The sponsorship was transferred to Shire Pharmaceuticals Ireland Limited, Ireland, in November 2017.

Recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein has been authorised in the EU as Takhzyro since 22 November 2018.

The sponsorship was transferred to Takeda Pharmaceuticals International AG Ireland Branch , Ireland in September 2021.

What is hereditary angioedema?

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.

What is the estimated number of patients affected by the condition?

At the time of designation, hereditary angioedema affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 512,900,000 (Eurostat 2015).

What treatments are available?

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 this medicine might be of significant benefit for patients with hereditary angioedema, with early studies showing that the medicine reduces angioedema attacks and compares favourably with existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to kallikrein proteins, and thereby block the activity of the kallikrein-kinin system. Since this system plays a role in causing the swelling and inflammation seen in angioedema, this medicine is expected to reduce the number of angioedema attacks.

What is the stage of development of this medicine?

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 the treatment of hereditary angioedema.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 September 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/15/1551: Public summary of opinion on orphan designation: Recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein for the treatment of hereditary angioedema

AdoptedReference Number: EMA/COMP/603277/2015

Key facts

• Active substance:
  Recombinant human IgG1 kappa light chain monoclonal antibody targeting plasma kallikrein (lanadelumab)
• Intended use:
  Treatment of hereditary angioedema
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/15/1551
• Date of designation:
  09/10/2015
• Sponsor:

  Takeda Pharmaceuticals International AG Ireland Branch; Block 2; Miesian Plaza; 50-58 Baggot Street Lower; Dublin 2; D02 HW68; Ireland; Tel: [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Takhzyro at the time of marketing authorisation, and confirmed that the orphan designation should be maintained.

More information is available in the Takhzyro: Orphan maintenance assessment report (initial authorisation)