EU/3/03/132

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Orphan designation

On 17 February 2003, orphan designation (EU/3/03/132) was granted by the European Commission to Combino Pharm, S.L., Spain, for caffeine citrate for the treatment of primary apnoea of premature newborns. The sponsorship was transferred to Chiesi Farmaceutici S.P.A., Italy, in January 2007.

What is primary apnoea of premature newborns?

Babies that are born well before the due date are called "premature newborns". These babies can have problems with breathing. They can stop breathing for a short time. When this lasts 20 seconds or longer, it is called apnoea. Generally, it is not clear what causes babies to stop breathing. When the causes are not known then this is called primary apnoea. Probably, it is due to the fact that the babies are born early and the organs and tissues of these babies are not yet mature. This includes the parts of the brain and the muscles that control the breathing. When babies stop breathing then this can cause very serious damage to the brain.

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

At the time of designation, primary apnoeas of premature newborns affected between 0.5 and 1.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of between 19,000 and 45,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 377,000,000 (Eurostat 2001) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

What treatments are available?

Several medicines and other treatments are used to treat premature babies who do not breathe well. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product subject of the application might be of potential significant benefit for the treatment of primary apnoeas of premature newborns. The main reason is that caffeine citrate would be widely available in the European Union. This will have to be proven at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Caffeine citrate stimulates the nervous system in the brain. In patients with primary apnoeas, caffeine can activate the part of the brain that controls breathing. Caffeine may also act in other ways. It may increase sensitivity to carbon dioxide that builds up in the body during apnoea. Patients might breathe more if a gas called carbon dioxide builds up in the body (as happens in apnoea). In addition it may improve respiratory muscle tonus and decrease diaphragm fatigue. The lungs could breathe in and out larger amount of air. The muscles used for breathing may contract more easily and may become less tired from breathing.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, clinical trials in premature newborns with primary apnoea were completed. Caffeine citrate has already been granted marketing authorisation in the condition subject of the application in France.

Caffeine citrate is designated as orphan in the United States of America (USA) in the treatment of apnoea of prematurity (20 September 1998). The same product has been licensed in the USA in the orphan condition on 21 September 1999.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 January 2002 recommending the granting of this designation.

Update: Caffeine citrate (Peyona, previously Nymusa) has been authorised in the EU since since 2 July 2009 for treatment of primary apnoea of premature newborns.

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>Caffeine citrate</p>
Active substanceCaffeine citrate
Medicine NamePeyona
Disease/conditionTreatment of primary apnoea of premature newborns
Date of decision17/02/2003
OutcomePositive
Orphan decision numberEU/3/03/132

Review of designation

Related information

Sponsor’s contact details:

Chiesi Farmaceutici S.P.A.
Via Palermo 26/A
43100 Parma
Italy
Telephone: +39 05 21 27 97 10
Telefax: +39 05 21 77 41 20
E-mail: info@chiesigroup.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.