EU/3/19/2205 - orphan designation for treatment of graft-versus-host disease

2-(3-(4-(1H-Indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide-methane sulfonic acid salt

Overview

On 17 October 2019, orphan designation EU/3/19/2205 was granted by the European Commission to Quality Regulatory Clinical Ireland Limited, Ireland, for 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide-methane sulfonic acid salt (also known as KD025) for the treatment of graft-versus-host disease.

The sponsorship was transferred to Sanofi-Aventis Groupe, France in March 2022.

What is graft-versus-host disease?

Graft-versus-host disease is a complication that can occur in patients who have had a transplant. In this disease, the transplanted cells recognise the patient’s body as ‘foreign’ and attack the patient’s organs, such as the stomach, gut, skin and liver, leading to organ damage. The disease may occur shortly after transplantation or later on, in which case more organs can be affected.

Graft-versus-host disease is a serious and life-threatening disease with a high mortality rate.

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

At the time of designation, graft-versus-host disease affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of designation, several medicines were authorised in the EU for the treatment of graft-versus-host disease, such as ciclosporin and corticosteroids. Treatment aimed to reduce the activity of transplanted cells involved in graft-versus-host disease, thereby reducing their ability to attack the patient's organs.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with graft-versus-host disease. Early data showed that patients’ condition improved and they used less corticosteroids after treatment with the medicine. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

The medicine blocks an enzyme called Rho-associated protein kinase 2 (ROCK2) that plays a role in the inflammation that occurs in graft-versus-host disease and leads to organ damage. By blocking this enzyme, the medicine is expected to help reduce inflammation and thereby relieve symptoms of the condition.

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, clinical trials with the medicine in patients with graft-versus-host disease were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of graft-versus-host disease. Orphan designation had been granted in the United States for chronic graft-versus-host disease.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 12 September 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/3/19/2205: Public summary of positive opinion for orphan designation of 2-(3-(4-(1H-Indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide-methane sulfonic acid salt for the treatment of graft-versus-host disease

Adopted Reference Number: EMADOC-628903358-1520

Key facts

• Active substance:
  2-(3-(4-(1H-Indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide-methane sulfonic acid salt
• Intended use:
  Treatment of graft-versus-host disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2205
• Date of designation:
  17/10/2019
• Sponsor:

  Sanofi Winthrop Industrie;