EU/3/19/2216: Orphan designation for the treatment of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK

Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 are a group of cancers affecting the bone marrow and the white blood cells. The condition is often characterised by high levels of a type of white blood cells called eosinophils, and is caused by changes (rearrangements) in the genes for some proteins called receptor tyrosine kinases (PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2). These proteins play a key role in the transmission of signals within cells that control cell growth, division and survival. As a result of the changes, these proteins are overactive and increase cell division, survival and the formation of new blood vessels, leading to cancer.

The condition is debilitating in the long term and life threatening due to its aggressive nature, with a high number of patients developing leukaemia that is resistant to conventional chemotherapy. It is associated with poor long-term survival.

At the time of designation, the condition affected less than 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 36,000 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 518,400,000 (Eurostat 2019).

At the time of designation, the main treatments for this condition 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 the condition. Early studies show that patients affected by myeloid or lymphoid neoplasms associated with FGFR1 rearrangement who received previous treatment responded to this medicine.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Pemigatinib belongs to a group of medicines called protein kinase inhibitors. It works by blocking protein kinases, including the overactive receptor tyrosine kinases in patients with the condition.

By blocking the overactive proteins, pemigatinib is expected to reduce the growth and spread of the cancer.

The effects of pemigatinib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with pemigatinib in patients with the condition were ongoing.

At the time of submission, pemigatinib was not authorised anywhere in the EU for the treatment of the condition. Orphan designation of pemigatinib had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 12 September 2019, 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.