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Please note that this product was withdrawn from the Union Register of orphan medicinal products in November 2022 on request of the Sponsor.
On 24 August 2018, orphan designation (EU/3/18/2057) was granted by the European Commission to Pharm Research Associates (UK) Limited, United Kingdom, for 1-(2-hydroxyethyl)-8-{[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy) phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide fumarate salt (also known as PCM-075) for the treatment of acute myeloid leukaemia.
Acute myeloid leukaemia (AML) is a cancer of the white blood cells (cells that fight infections). In patients with AML, the bone marrow (the spongy tissue inside the large bones, where blood cells are produced) produces abnormal, immature white blood cells. These abnormal cells quickly build up in large numbers in the bone marrow and are found in the blood.
AML is a long-term debilitating and life-threatening disease because these abnormal immature cells take the place of the normal blood cells, causing bleeding episodes, blood clots and a reduced ability to fight infections.
At the time of designation, AML affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 52,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).
Treatment for AML depends on a number of factors including the extent of the disease, whether it has been treated before, and the patient’s age, symptoms and general state of health. At the time of designation, the main treatments for AML were chemotherapy (medicines to treat cancer) and haematopoietic (blood) stem-cell transplantation (a procedure where the patient’s bone marrow is cleared of cells and replaced by stem cells to form new bone marrow that produces healthy blood cells).
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with AML because laboratory studies showed that combining this medicine with chemotherapy may reduce growth of the leukaemia and improve survival compared with chemotherapy alone. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine blocks the effect of an enzyme called polo-like kinase 1 (PLK1). PLK1 is found in excess amounts in the abnormal bone marrow cells of patients with AML, and plays an important role in allowing the leukaemia cells to grow and divide. By blocking PLK1, the medicine is expected to halt the growth of the leukaemia cells and cause them to die.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with AML were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for AML. Orphan designation of the medicine had been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 25 July 2018 recommending the granting of this designation.
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.
Pharmaceutical Research Associates Group B.V.
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
| Date | Update |
|---|---|
| November 2022 | Product withdrawn from the Union Register of orphan medicinal products on request of the Sponsor. |
| May 2019 | The sponsorship was transferred to Pharmaceutical Research Associates Group B.V., The Netherlands. |
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: