EU/3/19/2233: Orphan designation for the treatment of myelofibrosis

Myelofibrosis is a disease in which the bone marrow (spongy tissue inside the large bones where blood cells are produced) becomes dense and fibrous and starts producing abnormal immature blood cells that replace the normal blood cells. In myelofibrosis, some immature blood cells migrate from the bone marrow to other organs, such as the spleen and liver, where they mature. This causes the organs to become enlarged. Patients with the disease can develop several symptoms, including bone pain, tiredness, weakness, weight loss, fever and bleeding.

Myelofibrosis is a debilitating disease that is long-lasting and life-threatening because it can lead to severe anaemia (low red blood cell counts) and infections and can result in leukaemia (cancer of the white blood cells).

At the time of designation, myelofibrosis affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 518,400,000 (Eurostat 2019).

At the time of designation, busulfan, hydroxycarbamide and ruxolitinib were authorised in the EU for myelofibrosis. In addition, medicines were authorised to treat the symptoms, including erythropoietin (a hormone that stimulates the production of red blood cells) to treat anaemia, and surgery was used to remove the enlarged spleen. In some patients, haematopoietic (blood) stem-cell transplantation was used to treat the disease. This is a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor to form new bone marrow.

The sponsor has provided sufficient information to show that navitoclax might be of significant benefit for patients with myelofibrosis. Early studies showed a reduction in spleen size when navitoclax was given to patients already taking ruxolitinib or another treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.  

Navitoclax blocks the activity of a group of proteins called Bcl-2, which normally prevent cells from dying. When used together with chemotherapy or radiation, the medicine is expected to promote cell death and increase the ability of these treatments to kill cells, thereby increasing their effectiveness in treating the disease.     

The effects of navitoclax have been evaluated in experimental models.

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

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

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 7 November 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.