EU/3/09/628

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Orphan designation

On 30 April 2009, orphan designation (EU/3/09/628) was granted by the European Commission to Nova Laboratories Limited, United Kingdom, for mercaptopurine (oral suspension) for the treatment of acute lymphoblastic leukaemia.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

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 cells and 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 1.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 61,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 504,800,000 (Eurostat 2009).

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 used to kill cancer cells) followed by or combined with radiotherapy (using radiations to kill cancer cells). Bone-marrow transplantation was also used. This is a complex procedure where the bone marrow of the patient is destroyed and replaced with bone marrow from a matched donor.

The sponsor has provided sufficient information to show that mercaptopurine (oral suspension) might be of significant benefit for the patients because of the way in which the medicine is given. Mercaptopurine is already available in the European Union as tablets for the treatment of ALL. Mercaptopurine (oral suspension) is a liquid form of mercaptopurine, which could be given to children who have difficulty swallowing tablets. This may make it easier for children to take the medicine and allow the dose to be adjusted more precisely according to the patient’s weight. This assumption 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?

Mercaptopurine (oral suspension) is expected to work in the same way as mercaptopurine tablets.

Mercaptopurine is an anticancer medicine that belongs to the group ‘antimetabolites’. It works by interfering with the production of DNA within cells, preventing them from making more copies of their DNA. This means that cancer cells cannot divide and eventually die.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, a ‘bioequivalence’ study in adults had been planned, to find out whether the oral suspension of mercaptopurine was treated by the body in the same way as the tablets.

At the time of submission, mercaptopurine (oral suspension) was not authorised anywhere in the EU for ALL or designated as 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 4 March 2009 recommending the granting of this designation.

Update: Mercaptopurine (oral suspension) (Xaluprine) was authorised in the EU on 9 March 2012 for the treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children.

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.

Key facts

Product details for <p>Mercaptopurine (oral suspension)</p>
Active substanceMercaptopurine (oral suspension)
Medicine NameMercaptopurine Nova Laboratories
Disease/conditionTreatment of acute lymphoblastic leukaemia
Date of decision30/04/2009
OutcomePositive
Orphan decision numberEU/3/09/628

Review of designation

During its meeting of 6-8 September 2011, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/09/628 for Mercaptopurine Nova Laboratories (mercaptopurine (oral suspension) previously known as Novapurine) as an orphan medicinal product for the treatment of acute lymphoblastic 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 condition, and the existence of other satisfactory methods of treatment. As other satisfactory methods of treatment for patients with this condition 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 designation of the medicine be maintained.The 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.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Mercaptopurine Nova Laboratories for the treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children.

This falls within the scope of the product’s designated orphan indication, which is treatment of acute lymphoblastic leukaemia.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. Acute lymphoblastic leukaemia remains a condition that is a serious and potentially life-threatening disease, due to the excessive production of abnormal lymphocytes (a type of white blood cell) in the patient’s blood.

Prevalence of the condition

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of acute lymphoblastic leukaemia remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 1.2 people in 10,000. This is equivalent to a total of around 61,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of acute lymphoblastic leukaemia. The main treatment was chemotherapy (medicines used to kill cancer cells) followed by or combined with radiotherapy (using radiations to kill cancer cells). Bone marrow transplantation was also used. Mercaptopurine was already available in the EU as 50 mg tablets for the treatment of acute lymphoblastic leukaemia.

Significant benefit over existing treatments

Acute lymphoblastic leukaemia is the most common type of leukaemia in young children. The COMP concluded that the claim of a significant benefit of Mercaptopurine Nova Laboratories in acute lymphoblastic leukaemia is justified because the medicine offers a liquid form of mercaptopurine which may be given to children who have difficulty swallowing tablets, making it easier for them to take the medicine correctly and allowing the dose to be adjusted more precisely than the existing form (which is only available as 50 mg tablets). This makes a major contribution to patient care.

Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Mercaptopurine Nova Laboratories is of significant benefit for patients affected by acute lymphoblastic leukaemia.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Mercaptopurine Nova Laboratories still meets the criteria for designation as an orphan medicinal product and that Mercaptopurine Nova Laboratories should remain in the Community register of orphan medicinal products.

Sponsor’s contact details:

Nova Laboratories Limited
Martin House
Gloucester Crescent
Wigston
Leicester
LE18 4YL
United Kingdom
Tel. + 44 (0)1162 230100
Fax + 44 (0)1162 230101
E-mail: millie.sibson@novalabs.co.uk

Patients' organisations

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;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.