EU/3/15/1528

On 28 July 2015, orphan designation (EU/3/15/1528) was granted by the European Commission to Dicerna EU Limited, United Kingdom, for synthetic double-stranded RNA oligonucleotide specific to hydroxyacid oxidase 1 gene for the treatment of primary hyperoxaluria type 1.

What is primary hyperoxaluria type 1?

Primary hyperoxaluria type 1 is an inherited disease caused by the lack of a liver enzyme called alanine-glyoxylate aminotransferase (AGXT). This enzyme is needed to convert a substance called glyoxylate into glycine, an amino acid used for making enzymes and other proteins. Patients who lack this enzyme have high levels of oxalate in the urine, because glyoxylate instead of being converted into 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 type 1 is long-term debilitating and life threatening because of the high rate of kidney failure seen with the condition.

What is the estimated number of patients affected by the condition?

At the time of designation, primary hyperoxaluria type 1 affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to fewer than 5,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for treating primary hyperoxaluria type 1. 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.

How is this medicine expected to work?

This medicine is expected to reduce the body’s production of glyoxylate, the substance that is converted to oxalate in patients with primary hyperoxaluria type 1. 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.

What is the stage of development of this medicine?

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 type 1 had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for primary hyperoxaluria type 1 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 June 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.