EU/3/10/762

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Orphan designation

On 4 August 2010, orphan designation (EU/3/10/762) was granted by the European Commission to Wyeth Europa Limited, United Kingdom, for bosutinib for the treatment of chronic myeloid leukaemia.

The sponsorship was transferred to Pfizer Limited, United Kingdom, in May 2011.

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

What is chronic myeloid leukaemia?

Chronic myeloid leukaemia (CML) is a cancer of the white blood cells (cells that fight against infections). In patients with CML, the bone marrow (the spongy tissue inside the large bones) produces large numbers of abnormal, immature white blood cells called ‘blasts’, so there are too many of them circulating in the blood. These blast cells 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.

CML is most common in adults and older people, but children may also be affected. The disease usually develops very slowly, which is why it is called ‘chronic’. However, when it progresses, CML is a severe and life-threatening disease that is associated with poor overall survival.

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

At the time of designation, CML affected approximately 1.6 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 81,000 people, and is below the threshold 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 506,300,000 (Eurostat 2010).

What treatments are available?

Treatment for CML 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 treatments for CML were chemotherapy (medicines to treat cancer) and bone-marrow transplantation (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 bosutinib might be of significant benefit for patients with CML because early studies indicate that it might improve the treatment of patients who do not respond to existing treatments. 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?

Bosutinib is expected to work by blocking two types of enzymes called Src and Abl tyrosine kinases. These enzymes can be found in some receptors on the surface of leukaemia cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these enzymes, bosutinib is expected to control the spread of leukaemia cells.

What is the stage of development of this medicine?

The effects of bosutinib have been evaluated in experimental models.

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

At the time of submission, bosutinib was not authorised anywhere in the EU for CML. Orphan designation of bosutinib 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 6 May 2010 recommending the granting of this designation.

Update: Bosutinib (Bosulif) has been authorised in the EU since 27 March 2013 for for the treatment of adult patients with chronic-phase, accelerated-phase and blast-phase Philadelphia-chromosome-positive chronic myelogenous leukaemia previously treated with one or more tyrosine-kinase inhibitors and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

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 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.

Name Language First published Last updated
EU/3/10/762: Public summary of opinion on orphan designation of Bosutinib for the treatment of chronic myeloid leukaemia (English only) 10/08/2010 19/06/2013

Key facts

Product details for <p>Bosutinib</p>
Active substanceBosutinib
Medicine NameBosulif
Disease/conditionTreatment of chronic myeloid leukaemia
Date of decision04/08/2010
OutcomePositive
Orphan decision numberEU/3/10/762

Review of designation

On 12 February 2013, the Committee for Orphan Medicinal Products (COMP) finalised the review of the designation EU/3/10/762 for Bosulif (bosutinib) as an orphan medicinal product for the treatment chronic myeloid leukaemia (CML). 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 maintained1.


1The 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 Bosulif for: 

treatment of adult patients with chronic-phase, accelerated-phase, and blast-phase Philadelphia-chromosome-positive CML previously treated with one or more tyrosine-kinase inhibitors and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

This falls within the scope of the product’s designated orphan indications, which is CML.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2010. Although CML usually develops very slowly, which is why it is called ‘chronic’, when it progresses, it is a severe and life-threatening disease that is associated with poor overall survival.

Prevalence of the condition

The sponsor provided updated information on the prevalence of CML based on data from the Globocan 2008 database (which contains prevalence data for all types of leukaemia combined).

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of CML 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 approximately 1 person in 10,000. This is equivalent to a total of around 50,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, several medicines were authorised in the EU for the treatment of CML, including imatinib, nilotinib and dasatinib, which are orphan medicines known as ‘tyrosine-kinase inhibitors’ (TKIs). In addition, haematopoietic-stem-cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow) was used in some patients.

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Bosulif in CML is justified because this medicine represents a valuable alternative treatment option in a sub-group of patients identified as having an unmet medical need. This is based on the results of a study in 52 patients in the advanced stages of CML, for whom treatment with other TKIs was not considered suitable (due to concomitant medical conditions, disease resistance or the risk of severe side effects). The results showed that Bosulif was effective as a last treatment option for controlling CML in these patients.

Therefore, although other satisfactory methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Bosulif is of significant benefit for patients affected by CML.

Conclusions

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

Related information

Sponsor’s contact details:

Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom
Tel. +44 (0)1304 616161
Fax +44 (0)1304 652144
E-mail: orphan_enquiries@pfizer.com

Patient associations’ contact points:

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.