EU/3/16/1731: Orphan designation for the treatment of acute hepatic porphyria

Acute hepatic porphyria is a genetic condition in which patients lack certain enzymes needed to produce haem, a component of the blood pigment haemoglobin. As a result, substances for making haem accumulate in the body (particularly in the liver) and become toxic, causing attacks of severe abdominal pain, vomiting and nervous system disorders, such as seizures (fits), depression and anxiety. Some patients may also experience skin problems, with skin becoming oversensitive to light.
Acute hepatic porphyria is life-threatening due to the possibility of paralysis and respiratory arrest during attacks and debilitating in the long term because of symptoms such as pain, nausea, seizures and skin blistering.

At the time of designation, acute hepatic porphyria affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 513,700,000 (Eurostat 2016).

At the time of the orphan designation, Normosang (haem arginate) was authorised for treating acute hepatic porphyria in the EU. Patients also received supportive treatment to relieve the symptoms of the disease, including pain killers and antiemetics (to treat nausea and vomiting). In some patients, liver transplantation was performed.
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with the condition, with laboratory studies showing that it may be faster at reducing the levels of the toxic substances than the authorised product. In addition, a single injection of this medicine is expected to have a long-lasting effect. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a short, synthetic strand of genetic material called 'small interfering RNA' (siRNA) that has been designed to interfere with the production of an enzyme involved in an early step in making haem. By blocking this early step of haem production in patients with acute hepatic porphyria, the medicine is expected to prevent the next steps which produce substances that accumulate in the body and cause the symptoms of the disease.

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 acute hepatic porphyria had not yet started.
At the time of submission, the medicine was not authorised anywhere in the EU for acute hepatic porphyria or designated as an orphan medicinal product elsewhere for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2016 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.