EU/3/13/1175: Orphan designation for the treatment of autosomal dominant polycystic kidney disease

Polycystic kidney disease is an inherited condition marked by the growth of numerous fluid-filled cysts in the kidneys. The growth of cysts eventually affects kidney function and can cause the kidneys to fail. Symptoms include abdominal pain, problems with urinating, high blood pressure and infection.

In most cases polycystic kidney disease is 'autosomal dominant', which means that it is caused by gene mutations (defects) that are 'dominant' because a person can have the disease even if they have inherited a defective gene from only one parent. Autosomal-dominant polycystic kidney disease is caused by a mutation of either of two genes, PKD1 and PKD2.

Autosomal dominant polycystic kidney disease is debilitating in the long term and life-threatening because patients can develop kidney failure and problems with the heart and the gut.

At the time of designation, autosomal dominant polycystic kidney disease affected approximately 4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 205,000 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 512,200,000 (Eurostat 2013).

At the time of designation, there were no satisfactory treatments authorised for autosomal dominant polycystic kidney disease in the EU. Treatments that were available targeted symptoms of the disease and included antihypertensive medicines (for high blood pressure), pain killers, antibiotics for infection, dialysis and kidney transplantation.

Tolvaptan is already authorised in the EU for treating hyponatraemia (abnormally low sodium levels). It acts by blocking receptors in the kidney to which the hormone vasopressin attaches, which regulates the level of water and sodium in the body.

In autosomal dominant polycystic kidney disease, it is thought that the vasopressin receptors do not function as they should, leading to the formation of fluid-filled cysts. By blocking these receptors, tolvaptan is expected to help slow down cyst formation, thereby improving the symptoms of the disease.

The effects of tolvaptan have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with autosomal dominant polycystic kidney disease were ongoing.

At the time of submission, tolvaptan was not authorised anywhere in the EU for autosomal dominant polycystic kidney disease. Orphan designation had been granted in the United States and Japan for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 July 2013 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.