EU/3/20/2290: Orphan designation for the treatment of primary hyperoxaluria

Primary hyperoxaluria is an inherited disease in which patients suffer from recurring kidney and bladder stones which lead to pain, blood in the urine and frequent urinary tract infections. The disease is caused by the lack of certain enzymes produced by the liver that are needed to breakdown a substance called glyoxalate in the body. Instead of being converted into the amino acid glycine, glyoxalate is converted into excess oxalate. This can form calcium oxalate deposits, which cause kidney and bladder stones and may damage the kidneys and other organs.

Primary hyperoxaluria is long-term debilitating and life threatening because of the high rate of kidney failure seen in patients with the condition.

At the time of designation, primary hyperoxaluria 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, no satisfactory methods were authorised in the EU for treating primary hyperoxaluria. Different treatments were used to prevent the accumulation of calcium oxalate such as dietary changes, drinking plenty of fluids and taking vitamin B6. Kidney and liver transplantation have been possible options in patients with kidney failure.

This medicine is expected to block the action of an enzyme in the liver, LDH-5, that is involved in transforming glyoxalate into oxalate. By blocking the action of this enzyme, it is expected to reduce the amount of oxalate in the body and thereby limit the damage caused by oxalate deposits.

The effects of stiripentol have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with stiripentol in patients with primary hyperoxaluria were ongoing.

At the time of submission, stiripentol was authorised in the EU for a type of epilepsy called severe myoclonic epilepsy in infancy.

At the time of submission, stiripentol was not authorised anywhere in the EU for the treatment of primary hyperoxaluria or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 May 2020, 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.