EU/3/18/2052 - orphan designation for treatment of primary hyperoxaluria

Overview

On 31 July 2018, orphan designation (EU/3/18/2052) was granted by the European Commission to Dicerna EU Limited, United Kingdom, for synthetic double-stranded siRNA oligonucleotide directed against lactate dehydrogenase A mRNA and containing four modified nucleosides which form a ligand cluster of four N-acetylgalactosamine residues (also known as DCR-L1360) for the treatment of primary hyperoxaluria.

What is 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 glyoxylate in the body. Instead of being converted into the amino acid glycine, glyoxalate is therefore 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.

What is the estimated number of patients affected by 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).

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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 517,400,000 (Eurostat 2018).

What treatments are available?

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.

How is this medicine expected to work?

The conversion of glyoxylate to oxalate in patients with primary hyperoxaluria is controlled by an enzyme called lactate dehydrogenase. This medicine is made of a small strand of synthetic genetic material, called ‘small interfering RNA’ (siRNA), that is expected to enter liver cells and stop them from making lactate dehydrogenase. This in turn reduces the production of oxalate and so decreases the risk of calcium oxalate deposits from forming and damaging the kidneys and other organs.

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 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 21 June 2018 recommending the granting of this designation.

Key facts

• Intended use:
  Treatment of primary hyperoxaluria
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2052
• Date of designation:
  31/07/2018
• Sponsor:

  Dicerna EU Limited; 3rd Floor 11-12 St. James's Square; London SW1Y 4LB; United Kingdom; Tel. [phone]; E-mail: http://dicerna.com/contact/