EU/3/08/541 - orphan designation for treatment of erythropoietic protoporphyria

[Nle4, D-Phe7]-alfa-melanocyte stimulating hormone (afamelanotide)

Overview

On 8 May 2008, orphan designation (EU/3/08/541) was granted by the European Commission to Clinuvel UK Limited, United Kingdom, for [Nle4, D-Phe7]-alfa-melanocyte stimulating hormone for the treatment of erythropoietic protoporphyria.

[Nle4, D-Phe7]-alfa-melanocyte stimulating hormone has been authorised in the EU as Scenesse since 22 December 2014.

This medicine is now known as afamelanotide.

The sponsorship was transferred to Clinuvel Europe Limited, Ireland, in March 2019.

What is erythropoietic protoporphyria?

Porphyrias are a group of disorders of certain enzymes (proteins that speed up the conversion of certain substances into other substances) responsible for the chemical steps of heme production. Heme is normally present in the body and it is the basic component of haemoglobin, the molecule that carries oxygen in the blood. It is mainly found in the blood, bone marrow, and liver. The signs and symptoms of the disorder vary depending on which chemical step of the heme production that is affected. The porphyrias can be classified according to different criteria, such as the main location of the abnormal enzyme, the leading symptom, or the characteristics of its clinical presentation.

Erythropoietic protoporphyria is characterised by the involvement of blood forming organs, skin and the liver. In erythropoietic protoporphyria there is a lack of one enzyme important for the heme production, and therefore the the red blood cells accumulate substances that they normally do not accumulate. These substances also accumulate in the liver and in the skin. When skin is exposed to sunlight the accumulated substances react with light and cause symptoms such as burning sensation, itching, red skin and ulceration.

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

At the time of designation, erythropoietic protoporphyria affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of 10,000 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)

---

*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. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

What treatments are available?

No satisfactory methods exist that were authorised at the time of application. Avoidance of sunlight or strong light altogether is essential to manage the disease.

How is this medicine expected to work?

The product, [Nle4, D-Phe7] alpha-melanocyte stimulating hormone is a synthetic product with similar properties to the naturally occurring alpha-melanocyte stimulating hormone or melanotropin. This hormone is a naturally occurring hormone that stimulates the production of eumelanin in skin cells. Eumelanin, the natural black-brown pigment in the skin, has the capacity to protect cells from irradiation (sun exposure) and its damaging effects on the cellular genetic material. It is thought that the product stimulates eumelanin production in the skin cells and stops cellular damage by inhibiting (blocking) sun light's interaction with the accumulated substances that are found in the skin of patients with erythropoietic protoporphyria.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, clinical trials in patients with erythropoietic protoporphyria were ongoing.

[Nle4, D-Phe7] alpha-melanocyte stimulating hormone was not authorised anywhere worldwide for erythropoietic protoporphyria or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 March 2008 recommending the granting of this designation.

---

Update: [Nle4, D-Phe7]-alfa-melanocyte stimulating hormone, afamelanotide (Scenesse) has been authorised in the EU since 22 December 2014 for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP).

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 Community) 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/3/08/541: Public summary of positive opinion for orphan designation of [Nle4, D-Phe7]-alpha-melanocyte stimulating hormone for the treatment of erythropoietic protoporphyria

AdoptedReference Number: EMEA/COMP/160599/2008 Rev.2

Key facts

• Active substance:
  [Nle4, D-Phe7]-alfa-melanocyte stimulating hormone (afamelanotide)
• Medicine name:
  Scenesse
• Intended use:
  Treatment of erythropoietic protoporphyria
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/08/541
• Date of designation:
  08/05/2008
• Sponsor:

  Clinuvel Europe Limited; 10 Earlsfort Terrace; Dublin 2 D02 T380; Ireland; Tel: [phone]; E-mail: [e-mail]

Review of designation

During its meeting of 11 to 13 November 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/08/541 for Scenesse (afamelanotide)¹ as an orphan medicinal product for the treatment of erythropoietic protoporphyria. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained².

---

¹Previously known as [Nle4, D-Phe7]-alfa-melanocyte stimulating hormone.

²The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.