EU/3/04/210

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Orphan designation

On 29 July 2004, orphan designation (EU/3/04/210) was granted by the European Commission to PARI Aerosol Research Institute, Germany, for ciclosporin (for inhalation use) for the treatment of graft rejection after lung transplantation.

The name of the sponsor changed to PARI Pharma GmbH in 2007.

What is graft rejection in lung transplantation?

Lung transplantation is performed when, because of underlying conditions, the lungs are so damaged that one or both need to be replaced. It is most commonly performed in pulmonary emphysema, idiopathic pulmonary fibrosis, pulmonary hypertension and cystic fibrosis.

Rejection is the process by which the organ recipient's defence (immune) system recognises, becomes sensitised against, and attempts to eliminate the foreign donor organ.

It has been observed that at least one episode of rejection is common within the first year after a transplant. More than 80% of people who receive a lung transplant develop some symptoms of rejection within a month of transplantation. Symptoms include fever, shortness of breath, and weakness due to the non-optimal functioning of the transplanted lungs. Scar tissue may form in the small airways and gradually block them, possibly indicating gradual rejection.

The condition can be chronically debilitating and life threatening due to the high incidence of severe infections and graft rejection.

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

At the time of designation, graft rejection after lung transplantation affected approximately 0.05 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 2,300 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 based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

What treatments are available?

In order to preserve the new lung(s) in the recipient’s body, a suppression of the patient’s defence potential (immunosuppression) is induced after lung transplantation. The immunosuppressive agents already authorized for the use in the treatment of graft rejection are ciclosporin (intravenous administration) and corticosteroids. Other therapies that can be used are other immunosuppressive drugs such as methotrexate, or other methods that decrease the number of immune cells of the recipient, such as photopheresis and antilymphocyte antibodies.

Inhaled ciclosporin might be of potential significant benefit for the treatment of graft rejection after lung transplantation due to its new route of administration. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Ciclosporin for inhalation use is an immunosuppressive drug used to prevent the body from rejecting transplanted organs, as it suppresses the body’s natural reaction to the transplanted organ and is a component of most of the post transplant regimens.

Ciclosporin acts by inhibiting some special defence cells called lymphocyte T cells. It inhibits also the production of some special substances called lymphokines, which play a role in the defence reactions of the body. Ciclosporin for inhalation is meant to be used to treat patients who develop a rejection against their lung transplants by delivering the medicinal product directly to the lungs.

What is the stage of development of this medicine?

The effects of ciclosporin for inhalation use were evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials in patients with graft rejection after lung transplantation were initiated.

Ciclosporin for inhalation use was not marketed anywhere worldwide for graft rejection after lung transplantation or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 16 June 2004 recommending the granting of this designation.

Opinions on orphan medicinal products designations are based on the following cumulative 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.

 

Key facts

Product details for <p>Ciclosporin (inhalation use)</p>
Active substanceCiclosporin (inhalation use)
Medicine Name
Disease/conditionTreatment of graft rejection after lung transplantation
Date of decision29/07/2004
OutcomePositive
Orphan decision numberEU/3/04/210

Review of designation

Sponsor’s contact details

PARI Pharma GmbH
Moosstrasse 3
82319 Starnberg
Germany
Telephone: +49 89 742 846 51
Telefax: +49 89 742 846 30
E-mail: info@paripharma.com

Patients’ organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.