EU/3/02/103 - orphan designation for treatment of acute intermittent porphyria
recombinant human porphobilinogen deaminase
Orphan
Human
Overview
On 12 June 2002, orphan designation (EU/3/02/103) was granted by the European Commission to HemeBiotech A/S, Denmark, for recombinant human porphobilinogen deaminase (rhPBGD) for the treatment of acute intermittent porphyria.
The sponsorship was transferred to Chiesi Farmaceutici S.p.A., Italy, in July 2018.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in July 2020 on request of the Sponsor.
Acute intermittent porphyria is a clinical manifestation of a genetic disorder affecting the production of an enzyme involved in the synthesis of heme (component of molecules such as hemoglobin or myoglobin): the porphobilinogen deaminase enzyme (PBGD). The genetic disorder is caused by mutation in the PBGD gene, resulting in a 50% reduction of enzymatic activity. This may lead to an increase in blood and urinary concentrations of heme precursors (products leading to heme synthesis such as porphobilinogen or PBG, and delta-aminolevulinic acid or ALA) and a deficit in heme synthesis.
Lack of heme and/or accumulation of heme precursors (such as PBG and ALA) are the main hypotheses to explain development of symptoms of acute intermittent porphyria. Manifestations of the disease are usually linked to triggering factors such as hormonal changes.
The first treatment objective is to remove the precipitating factors. A high carbohydrate (sugars) intake produces a decrease in production of heme precursors and clinical improvement. Intravenous heme arginate, an inhibitor of ALA synthetase, is also available and authorised for the treatment of acute intermittent porphyria in the Community.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that rhPBGD might be of potential significant benefit for the treatment of acute intermittent porphyria, particularly in terms of its novel mechanism of action.
According to the information provided by the sponsor, acute intermittent porphyria was considered to affect about 38,000 persons in the European Union.
*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.
Administration of rhPBGD is expected to act by decreasing plasma concentrations of heme precursors.
The effects of rhPBGD have been evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials in patients with attacks of acute intermittent porphyria had been initiated.
rhPBGD had not been marketed anywhere worldwide for acute intermittent porphyria or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 30 April 2002 a positive opinion recommending the grant of the above-mentioned designation.
(i) the seriousness of the condition, (ii) the existence or not of alternative methods of diagnosis, prevention or treatment and (iii) either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.
Designated orphan medicinal products are still investigational products which have been considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.
Key facts
- Active substance
- recombinant human porphobilinogen deaminase
- Intended use
- Treatment of acute intermittent porphyria
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/02/103
- Date of designation
- Sponsor
Chiesi Farmaceutici S.p.A.
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:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
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: