EU/3/19/2201 - orphan designation for treatment of C3 glomerulopathy

Poly(oxy-1,2-ethanediyl), alpha-hydro-omega-hydroxy-,15,15'-diester with N-acetyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-alpha-aspartyl-L-tryptophylglycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-L-threonyl-2-[2-(2-aminoethoxy)ethoxy]acetyl-N6-carboxy-L-lysinamide cyclic (2.fwdarw.12)-(disulfide); where two identical synthetic peptide domains are covalently linked at the ends of the polyethylene glycol chain (pegcetacoplan)

Overview

On 21 August 2019, orphan designation EU/3/19/2201 was granted by the European Commission to Apellis Ireland Limited, Ireland, for poly(oxy-1,2-ethanediyl), alpha-hydro-omega-hydroxy-,15,15'-diester with N-acetyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-alpha-aspartyl-L-tryptophylglycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-L-threonyl-2-[2-(2-aminoethoxy)ethoxy]acetyl-N6-carboxy-L-lysinamide cyclic (2.fwdarw.12)-(disulfide); where two identical synthetic peptide domains are covalently linked at the ends of the polyethylene glycol chain (also known as APL-2) for the treatment of C3 glomerulopathy.

This medicine is now known as pegcetacoplan.

The sponsorship was transferred to Swedish Orphan Biovitrum AB (publ), Sweden in January 2021.

What is C3 glomerulopathy?

C3 glomerulopathy is a condition in which a part of the body's immune system (the body's natural defences) known as the complement system is overactive. As a result, breakdown products of a component of the system called C3 build up in the kidneys, damaging them and reducing their function.

Patients with C3 glomerulopathy usually have signs of problems relating to poor kidney function, such as blood or protein in urine, high blood pressure, blurred vision and swelling in the hands and feet.

C3 glomerulopathy is life threatening and debilitating in the long term because it can lead to kidney failure.

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

At the time of designation, C3 glomerulopathy affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 people¹, 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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¹Disclaimer: 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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of orphan designation, no satisfactory treatments were authorised in the EU for C3 glomerulopathy. Because the disease involves the body's immune system, immunosuppressant medicines (that reduce the activity of the immune system) were usually used. Other treatments included plasmapheresis (a procedure to remove unwanted substances from plasma, the liquid part of the blood), infusion of healthy plasma, and medicines to reduce blood pressure and protein in the urine. Some patients developing end-stage kidney disease received dialysis and kidney transplantation.

How is this medicine expected to work?

The medicine works by reducing the abnormal activity of the complement system, which reduces the breakdown of C3. This is expected to prevent C3 breakdown products building up in the kidneys thereby reducing damage in the kidneys and the problems caused by the kidneys not working well enough.

What is the stage of development of this medicine?

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with this medicine in patients with C3 glomerulopathy were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for the treatment of C3 glomerulopathy. Orphan designation had been granted in the United States for C3 glomerulopathy.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 July 2019, 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/3/19/2201: Public summary of positive opinion for orphan designation of poly(oxy-1,2-ethanediyl), alpha-hydro-omega-hydroxy-,15,15'-diester with N-acetyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-alpha-aspartyl-L-tryptophylgl

Reference Number: EMADOC-628903358-1305

Key facts

• Active substance:
  Poly(oxy-1,2-ethanediyl), alpha-hydro-omega-hydroxy-,15,15'-diester with N-acetyl-L-isoleucyl-L-cysteinyl-L-valyl-1-methyl-L-tryptophyl-L-glutaminyl-L-alpha-aspartyl-L-tryptophylglycyl-L-alanyl-L-histidyl-L-arginyl-L-cysteinyl-L-threonyl-2-[2-(2-aminoethoxy)ethoxy]acetyl-N6-carboxy-L-lysinamide cyclic (2.fwdarw.12)-(disulfide); where two identical synthetic peptide domains are covalently linked at the ends of the polyethylene glycol chain (pegcetacoplan)
• Intended use:
  Treatment of C3 glomerulopathy
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2201
• Date of designation:
  21/08/2019
• Sponsor:

  Swedish Orphan Biovitrum AB (publ)

Review of designation

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