EU/3/09/715 - orphan designation for treatment of acute lymphoblastic leukaemia

Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] (ponatinib)

Overview

On 2 February 2010, orphan designation (EU/3/09/715) was granted by the European Commission to Ariad Pharma Ltd, United Kingdom, for benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] (ponatinib) for the treatment of acute lymphoblastic leukaemia.

Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] (ponatinib) for the treatment of acute lymphoblastic leukaemia has been authorised in the EU as Iclusig since 1 July 2013.

This medicine is now known as ponatinib.

Please note that this product was withdrawn from the Community Register of designated orphan medicinal products in July 2023 at the end of the 10-year period of market exclusivity.

What is acute lymphoblastic leukaemia?

Acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells called lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so there are too many of them circulating in the blood. These abnormal lymphocytes are not fully developed and do not work properly. Over a period of time, they replace the normal white blood cells, red blood cells and platelets in the bone marrow (the spongy tissue inside the large bones in the body).

ALL is the most common type of leukaemia in young children, but the disease also affects adults, especially those aged 65 years and older. Many people with ALL can be cured. However, despite the available treatments, ALL remains a serious and life-threatening disease in some patients.

What is the estimated number of patients affected by the condition?

At the time of designation, ALL affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

What treatments are available?

Treatment for ALL is complex and 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 treatment of ALL was chemotherapy (medicines to treat cancer) followed by or combined with radiotherapy (treatment with radiation). Bone-marrow transplantation was also used. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with healthy bone marrow from a matched donor.

The sponsor has provided sufficient information to show that benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] might be of significant benefit for patients with ALL because it may represent an alternative treatment for patients with this condition, and because early studies indicate that it might be used in patients who do not respond to existing treatments. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] belongs to a group of medicines called 'protein-tyrosine-kinase inhibitors'. These medicines work by blocking enzymes known as protein kinases. This medicine is mainly expected to work by blocking the protein kinase called 'BCR-ABL' kinase. This enzyme is produced by leukaemia cells, and causes them to multiply uncontrollably. By blocking BCR-ABL kinase, as well as other kinases, the medicine is expected to help to control the spread of leukaemia cells.

What is the stage of development of this medicine?

The effects of benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the designated product in patients with ALL were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for ALL 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 3 December 2009 recommending the granting of this designation.

Update: Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] (Iclusig) was authorised in the EU on 1 July 2013. Iclusig is indicated in adult patients with Philadelphia-chromosome-positive ALL who are resistant to dasatinib, who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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 Community) 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.

EU/3/09/715: Public summary of opinion on orphan designation of benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] for the treatment of acute ly...

AdoptedReference Number: EMA/COMP/804144/2009 Rev.2

Key facts

• Active substance:
  Benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl] (ponatinib)
• Medicine name:
  Iclusig
• Intended use:
  Treatment of acute lymphoblastic leukaemia
• Orphan designation status:
  Expired
• EU designation number:
  EU/3/09/715
• Date of designation:
  02/02/2010
• Sponsor:

  Incyte Biosciences Distribution B.V.; Paasheuvelweg 25; 1105 BP Amsterdam; Noord-Holland; The Netherlands; E-mail: [e-mail]

Review of designation

During its meeting of 16-17 April 2013, the Committee for Orphan Medicinal Products (COMP) reviewed the designations EU/3/09/715 and EU/3/09/716 for Iclusig (ponatinib¹) as an orphan medicinal product for the treatment of acute lymphoblastic leukaemia and of chronic myeloid leukaemia. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the conditions, and the existence of other methods of treatment. As other satisfactory methods of treatment for patients with these conditions are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designations of the medicine be maintained².

---

¹Previously known as benzamide, 3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl].
²The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.