EU/3/15/1451: Orphan designation for the treatment of Alport syndrome

Alport syndrome is an inherited condition caused by a mutation (defect) in one of a group of genes responsible for producing type IV collagen, a fibrous protein needed to form the membranes that separate and support cells in organs such as the kidney, ear and eye. In patients with Alport syndrome, these membranes have an abnormal structure, so the organs cannot develop and function properly. Patients therefore experience internal scarring of the kidney and gradually worsening kidney function that eventually results in kidney failure. Patients also suffer hearing loss and may develop cataracts and visual impairment.

Alport syndrome is a long-term debilitating disease due to the progressive kidney damage and impaired hearing and vision; it is potentially life threatening because it results in kidney failure that requires dialysis or transplantation.

At the time of designation, Alport syndrome affected not more than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 103,000 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 512,900,000 (Eurostat 2015).

At the time of designation, no satisfactory methods of treatment were authorised in the EU for patients affected by the condition. Patients were given medicines that act on the renin-angiotensin system (RAS), which may if started early enough help slow the progression of kidney disease.

Scarring and kidney damage in patients with long-term kidney disorders, including Alport syndrome, is associated with production of high levels of a type of genetic material (RNA) called micro-RNA21.

This medicine is a short strand of synthetic RNA-like material that is able to attach to and neutralise micro-RNA21. By neutralising micro-RNA21, it is expected to reduce the development of scarring and kidney damage in patients with the disease, and so slow the loss of kidney function and delay the need for transplantation or dialysis.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with this medicine in patients with Alport syndrome had been started.

At the time of submission, 5'-A_SC_SA_ST_SC_SA_SG_ST_SC_ST_SG_SA_SU_SA_SA_SG_SC_ST_SA-3' was not authorised anywhere in the EU for Alport syndrome. 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 12 February 2015 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.