EU/3/18/2049 - orphan designation for treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency

recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1 fused to the Fc fragment of IgG1

Overview

On 31 July 2018, orphan designation (EU/3/18/2049) was granted by the European Commission to Inozyme Pharma Ireland Ltd, Ireland, for recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1 fused to the Fc fragment of IgG1 (also known as INZ-701) for the treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency.

What is ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency?

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency is an inherited disorder in which the body does not produce the enzyme ENPP1. The enzyme is important for preventing harmful calcification (build-up of calcium) in soft tissues and for controlling mineralisation (take up of minerals) in bones. ENPP1 deficiency can lead either to a problem called generalised arterial calcification of infancy (GACI) or to autosomal recessive hypophosphataemic rickets (ARHR).

GACI starts in very young babies whose arteries become narrower and stiffer, increasing the heart’s workload. Patients develop very high blood pressure, heart failure (when the heart no longer works as well as it should), breathing difficulty, oedema (build-up of fluid in body tissues) and skin and lips becoming blue. ARHR, which starts appearing in early childhood, results in slow or reduced growth, bone abnormalities and pain which get worse with time. Adults develop osteomalacia (bones becoming soft and weak).

ENPP1 deficiency is a long-term debilitating and life-threatening disease that can lead to death in infancy.

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

At the time of designation, ENPP1 deficiency affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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).

---

* 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 the treatment of ENPP1 deficiency. Treatment was mainly supportive to manage symptoms of the condition.

How is this medicine expected to work?

The medicine consists of a synthetic form of the enzyme ENPP1. The enzyme is attached to a protein called Fc fragment to help it stay in the body for longer. By replacing the missing enzyme in patients with ENPP1 deficiency, the medicine is expected to reduce symptoms of the condition.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with ENPP1 deficiency had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for ENPP1 deficiency 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.

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.

EU/3/16/1800: Public summary of opinion on orphan designation: Recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1 fused to the Fc fragment of IgG1 for the treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency

Adopted Reference Number: EMA/454552/2018

Key facts

• Active substance:
  recombinant human ectonucleotide pyrophosphatase/phosphodiesterase 1 fused to the Fc fragment of IgG1
• Intended use:
  treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 deficiency
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/18/2049
• Date of designation:
  31/07/2018
• Sponsor:

  Inozyme Pharma Ireland Ltd; 29 Earlsfort Terrace; Dublin 2; Ireland; Tel. [phone]; E-mail: [e-mail]

Review of designation

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