Overview
On 15 January 2015, orphan designation (EU/3/14/1427) was granted by the European Commission to AM-Pharma BV, the Netherlands, for recombinant human alkaline phosphatase for the treatment of hypophosphatasia.
Hypophosphatasia is an inherited condition affecting the bones. It is caused by defects in the gene responsible for producing 'tissue non-specific alkaline phosphatase (TNSALP)', an enzyme that is involved in the development of bone, particularly the hardening of the bones. Patients with hypophosphatasia have low levels TNSALP, which leads to brittle bones. Symptoms include early loss of teeth, malformed (unusually shaped) bones and frequent bone fractures (breaks).
There are five forms of the disease. Perinatal and infantile hypophosphatasia affect unborn babies and children, and are life threatening either in the womb or in early infancy because of the incomplete development of the bones and lungs. The other three forms (childhood and adult hypophosphatasia, and odontohypophosphatasia) are generally not lethal but are debilitating and long lasting.
At the time of designation, hypophosphatasia affected approximately 0.03 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,500 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).
At the time of submission of the application for orphan designation, there were no satisfactory methods authorised for the treatment of hypophosphatasia. Patients received supportive treatment such as plaster casts for broken bones, controlling pain and maintaining the levels of calcium in the blood by giving calcium supplements. Patients were sometimes treated with surgery, and dental hygiene was carefully monitored.
This medicine is made up of an enzyme that is similar to the one that is missing in patients with hypophosphatasia. The medicine is expected to replace the missing enzyme, improving bone development and making them harder.
The medicine is made by a method known as 'recombinant DNA technology': it is made by cells into which a gene (DNA) has been introduced that makes them able to produce the enzyme.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with hypophosphatasia were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for hypophosphatasia 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 11 December 2014 recommending the granting of this designation.
- 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
- Active substance
- Recombinant human alkaline phosphatase
- Intended use
- Treatment of hypophosphatasia
- Orphan designation status
- Positive
- EU designation number
- EU/3/14/1427
- Date of designation
- Sponsor
AM-Pharma BV
Rumpsterweg 6
3891 AK Bunnik
The Netherlands
Tel. +31 30 2289 222
Fax +31 30 2289 220
E-mail: info@am-pharma.com
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: