EU/3/08/541: Orphan designation for the treatment of 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.

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 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

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.

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.

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).

• 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.