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Orphan designation

On 28 August 2006, orphan designation (EU/3/06/391) was granted by the European Commission to Nektar Therapeutics UK Ltd, United Kingdom, for amphotericin B (for inhalation use) for the prevention of pulmonary fungal infections in patients deemed at risk.

The sponsorship was transferred to Kendle International Ltd, United Kingdom, in August 2010 and subsequently to Novartis Europharm Limited, United Kingdom, in March 2014.

The sponsorship was transferred to Novartis Europharm Limited, Ireland, in May 2018.

What is pulmonary fungal infection in patients deemed at risk?

Every day we inhale many sorts of particles that are present in the environment, including spores, which are single dormant fungal cells. In healthy individuals these spores normally can’t cause any harm because they are taken care of by our immune system (the body’s natural defence system). In patients that for some reason have a weakened immune system (are immunosuppressed), however, these spores can become activated and the condition (colonisation) can develop into a lung fungal infection. There are several conditions that can cause immunosuppression including medicines that prevent transplanted organ rejection, blood cancers (leukaemias and lymphomas) and cancer treatments (chemotherapy), human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). Symptoms of pulmonary fungal infection are shortness of breath, chest pain, cough, fever and weight loss. Pulmonary fungal infection is life-threatening due to the high risk of severe pulmonary disease and fungal sepsis (infection of the blood).

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of developing pulmonary fungal infection was estimated to be approximately 2.2 people in 10,000 in the European Union (EU). This was equivalent to a total of around 103,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

What methods of prevention are available?

Currently the same medicinal products that are authorised for the treatment of pulmonary fungal infections, are also used for prevention including amphotericin B used intravenously. These products aim to kill the fungal cells through interfering with its cell membrane, the layer that surrounds and encapsulates the fungal cell.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that amphotericin B might be of potential significant benefit for the prevention of pulmonary fungal infection in patients deemed at risk, mainly because it may have less side effects than the product used intravenously. This 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?

Amphotericin B is a molecule that is designed to bind to substances called sterols. These are lipid structures found mainly in the outer membranes of cells. In humans the most abundant sterol is cholesterol and in fungal cells it is a related molecule called ergosterol. When amphotericin B binds to ergosterol it disrupts the ordered structure of the cell membrane and small holes (pores) are created. According to the sponsor, amphotericin B will kill the fungal cells by this mechanism and thus prevent them from colonising the lungs and causing an infection. Amphotericin B (for inhalation use) will only be delivered locally to the lungs.

What is the stage of development of this medicine?

The effects of amphotericin B (for inhalation use) were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients deemed at risk of developing pulmonary fungal infections were ongoing.

Amphotericin B (for inhalation use) was not authorised anywhere worldwide for the prevention of pulmonary fungal infections in patients deemed at risk, at the time of submission. Orphan designation of amphotericin B was granted in the United States for prevention of pulmonary fungal infections in patients at risk for aspergillosis due to immunosuppressive therapy including those receiving organ or stem cell transplants, or treated with chemotherapy or radiation for haematologic malignancies.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 July 2006 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 Community) 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>Amphotericin B (for inhalation use)</p>
Active substanceAmphotericin B (for inhalation use)
Medicine Name
Disease/conditionPrevention of pulmonary fungal infection in patients deemed at risk
Date of decision28/08/2006
Orphan decision numberEU/3/06/391

Review of designation

Sponsor’s contact details:

Novartis Europharm Limited
Vista Building
Elm Park
Merrion Road
Dublin 4
Tel. +41 (0)61 324 11 11

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.