EU/3/17/1888: Orphan designation for the treatment of distal renal tubular acidosis

Distal renal tubular acidosis is a kidney disease in which the kidneys do not remove acid through the urine well enough. This results in a build-up of acid in the blood, which leads to a range of symptoms including hearing and growth problems, vomiting, kidney stones and lack of alertness.

The disease also causes levels of potassium in the blood to fall, which can lead to muscle weakness and paralysis. One type of distal renal tubular acidosis, usually first detected in babies, is caused by mutations (changes) in certain genes. A second type, usually seen in adults, can be caused by several other diseases including some autoimmune diseases (diseases caused by the body's defence system attacking normal tissue).

Distal renal tubular acidosis is debilitating due to the problems it causes with hearing, growth, the kidneys and bone development and can be life-threatening in some patients.

At the time of designation, distal renal tubular acidosis affected approximately 2.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 108,000 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 515,700,000 (Eurostat 2017).

At the time of designation, treatments containing salts, such as potassium/sodium citrate and potassium/sodium bicarbonate, used on their own or in different combinations, were used in patients with distal renal tubular acidosis.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with distal renal tubular acidosis because preliminary data show that it stops the blood becoming too acidic, and its effects compare well with currently authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is a combination of two salts, tripotassium citrate monohydrate (also known as potassium citrate) and potassium hydrogen carbonate (also known as potassium bicarbonate), that are taken by mouth and released slowly into the body over a few hours. Because the combination is alkaline and contains potassium, it is expected to both neutralise excess acid in the blood and restore levels of potassium.

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 distal renal tubular acidosis were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for distal renal tubular acidosis 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 12 May 2017 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.