On 26 October 2018, orphan designation (EU/3/18/2079) was granted by the European Commission to Spark Therapeutics Ireland Limited, Ireland, for recombinant adeno-associated viral vector containing a bioengineered capsid and a codon-optimised expression cassette to drive the expression of the SQ form of a B-domain deleted human coagulation factor VIII (also known as SPK-8011) for the treatment of haemophilia A.
The sponsor’s address was updated in April 2019.
Haemophilia A is an inherited bleeding disorder that is caused by the lack of factor VIII, which is one of the proteins involved in the blood coagulation (clotting) process. Patients with haemophilia A are prone to bleeding and bleed for a long time after injury or surgery. Bleeding can also happen within muscles or in the joints, such as the elbows, knees and ankles. This can lead to permanent injury if it happens repeatedly.
Haemophilia A is a debilitating disease that is life long and may be life threatening because bleeding can occur in the brain, spinal cord or gut.
At the time of designation, haemophilia A affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 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, medicines containing factor VIII were authorised in the EU for the treatment of haemophilia A, to replace the missing protein. However, factor VIII medicines did not work in some patients with haemophilia A because the immune system (the body’s natural defences) can produce ‘inhibitors’ (antibodies) against factor VIII which stop the factor VIII medicine from working. In these cases, different blood clotting factors or other treatments needed to be used, either alone or as part of a combination treatment.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with haemophilia A because preliminary results indicate that it can improve the levels of factor VIII circulating in the blood in the long term.
This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Patients with haemophilia A cannot make enough functioning factor VIII because the gene for producing the clotting factor is damaged.
This medicine is made of a virus that contains normal copies of the gene responsible for producing factor VIII. When injected into the patient's vein, it is expected that the virus will be carried into the liver cells and start producing factor VIII. It is expected that a single dose of the medicine will maintain raised levels of factor VIII for a long time thereby reducing bleeding.
The type of virus used in this medicine (‘adeno-associated virus’) does not cause disease in humans.
The effects of this medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients with haemophilia A was ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for haemophilia A. Orphan designation of the medicine had been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 September 2018 recommending the granting of this designation.
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.
Spark Therapeutics Ireland Limited
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: