EU/3/16/1637: Orphan designation for the treatment of primary hyperoxaluria

Primary hyperoxaluria is an inherited disease caused by the lack of certain enzymes needed to breakdown a substance called glyoxylate in the body. Patients with primary hyperoxaluria have high levels of oxalate in the urine, because glyoxylate instead of being converted into the amino acid glycine is converted into excess oxalate. Oxalate can form calcium oxalate deposits, which can cause stones in the kidney and urinary tract (structures that carry urine) as well as injury to other organs such as the heart, eyes, bones and skin. Characteristic symptoms of the disease include blood in the urine, tummy pain and frequent urinary tract infections.

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 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,600 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 513,700,000 (Eurostat 2016).

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 certain cases.

This medicine is expected to reduce the body's production of glyoxylate, the substance that is converted to oxalate in patients with primary hyperoxaluria. Normally, production of glyoxylate is regulated by an enzyme called hydroxyacid oxidase (also known as glycolate oxidase). The medicine is designed to attach specifically to genetic material in the cell responsible for the production of hydroxyacid oxidase. This blocks production of the enzyme so that less glyoxylate is created, thereby reducing the production of oxalate. Therefore, the chance of forming calcium oxalate deposits is reduced.

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 the medicine in patients with primary hyperoxaluria had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for primary hyperoxaluria 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 18 February 2016 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.