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Orphan designation

On 2 April 2012, orphan designation (EU/3/12/955) was granted by the European Commission to Giampaolo Merlini, Italy, for doxycycline hyclate for the treatment of familial amyloid polyneuropathy.

What is familial amyloid polyneuropathy?

Familial amyloid polyneuropathy (FAP) is a hereditary (‘familial’) disease caused by a defective gene for transthyretin, a protein that transports various substances in the blood. Transthyretin is primarily produced in the liver.

Patients with FAP have an abnormal transthyretin protein that breaks up easily and accumulates in various tissues in the body, especially tissues of the nervous system, in the form of insoluble, waxy ‘amyloid’ deposits. The condition mainly affects the heart and the nervous system causing symptoms such as muscle weakness in the limbs and, at later stages, inability to walk, problems affecting the stomach and the gut (leading to malnutrition), and bladder dysfunction.

FAP is a long-term debilitating disease due to the progressive worsening of nervous system symptoms. It is also life threatening because the amyloid deposits may accumulate in the heart and cause fatal heart conditions.

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

At the time of designation, FAP affected approximately 1.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 71,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, the only medicine authorised in the EU to treat FAP was Vyndaqel (tafamidis). The only other treatment option was liver transplantation.

The sponsor has provided sufficient information to show that doxycycline hyclate might be of significant benefit for patients with FAP because early studies show that it works in a different way to the existing medicine and might improve the treatment of patients with this condition. 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?

Doxycycline is a widely used antibiotic that belongs to the class ‘tetracyclines’. In FAP, doxycycline is expected to work by disrupting the aggregation (sticking together) of abnormal transthyretin protein, which in turn is expected to make the ‘amyloid’ deposits dissolve. This is expected to reduce the symptoms of FAP.

What is the stage of development of this medicine?

The effects of doxycycline hyclate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with doxycyline hyclate in patients with FAP were ongoing.

At the time of submission, doxycycline was authorised for other indications throughout Europe.

At the time of submission, doxycycline hyclate was not authorised anywhere in the EU for FAP or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 December 2011 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.

Key facts

Product details for <p>Doxycycline hyclate</p>
Active substanceDoxycycline hyclate
Medicine Name
Disease/conditionTreatment of familial amyloid polyneuropathy
Date of decision02/04/2012
Orphan decision numberEU/3/12/955

Review of designation

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

Sponsor’s contact details:

Amyloidosis Research and Treatment Center
Foundation IRCCS Policlinico
San Matteo and University of Pavia
Viale Golgi, 19
27100 Pavia
Telephone: +39 0382 502995
Telefax: +39 0382 502990

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.