EU/3/12/1063

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Orphan designation

On 8 November 2012, orphan designation (EU/3/12/1063) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for panobinostat for the treatment of multiple myeloma.

Update: panobinostat (Farydak) has been authorised in the EU since 28 August 2015. Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent.

What is multiple myeloma?

Multiple myeloma is a cancer of a type of white blood cells called plasma cells. Plasma cells are found in the bone marrow, the spongy tissue inside the large bones in the body. In multiple myeloma, the division of plasma cells becomes out of control, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. This interferes with production of normal white blood cells, red blood cells and platelets (components that help the blood to clot), leading to complications such as anaemia (low red blood cell counts), bone pain and fractures, raised blood calcium levels and kidney dysfunction.

Multiple myeloma is a debilitating and life-threatening disease because it disrupts the normal functioning of the bone marrow, leads to bone destruction and causes kidney failure.

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

At the time of designation, multiple myeloma affected not more than 3.2 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 163,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of designation, several medicines were authorised for multiple myeloma in the EU. The main treatment for multiple myeloma was chemotherapy (medicines to treat cancer) usually combined with steroids to reduce the activity of the immune system, the body’s natural defences. 

Where chemotherapy did not work, some patients received an allogeneic stem-cell transplant (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow). 

Radiotherapy (using radiation to kill cancer cells) was used to treat pain and weakened bones. Interferon alfa, a protein normally produced by the body during viral infections, was sometimes used in combination with chemotherapy.

The sponsor has provided sufficient information to show that panobinostat might be of significant benefit for patients with multiple myeloma because early studies show that, when used in combination with existing chemotherapy treatment, it may be effective in treating the disease when it has come back or does not respond to other treatments alone. 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?

Panobinostat is expected to work by blocking the activity of proteins called histone deacetylases (HDACs), which are involved in turning genes ‘on’ and ‘off’ within cells. 

In multiple myeloma, panobinostat is expected to have several actions, including keeping the genes that suppress the division and growth of the cancer cells switched ‘on’. This is expected to lead to a reduction in the growth and division of the cancer cells, thereby slowing down the growth of the cancer.

What is the stage of development of this medicine?

The effects of panobinostat have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with panobinostat in patients with multiple myeloma were ongoing.

At the time of submission, panobinostat was not authorised anywhere in the EU for multiple myeloma. Orphan designation of panobinostat had been granted in the United States of America for multiple myeloma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 October 2012 recommending the granting of this designation.

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/3/12/1063: Public summary of opinion on orphan designation: Panobinostat for the treatment of multiple myeloma (English only) 12/12/2012 11/02/2015

Key facts

Product details for <p>Panobinostat</p>
Active substancePanobinostat
Medicine NameFarydak
Disease/conditionTreatment of multiple myeloma
Date of decision08/11/2012
OutcomePositive
Orphan decision numberEU/3/12/1063

Review of designation

During its meeting of 14 to 16 July 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/12/1063 for Farydak (panobinostat) as an orphan medicinal product for the treatment of multiple myeloma (also known as plasma cell myeloma). 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 methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with multiple myeloma. 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 Farydak for:

‘Farydak, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent’.

This falls within the scope of the product’s designated orphan indication, which is: ‘multiple myeloma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. Multiple myeloma remains a debilitating and life-threatening disease because it disrupts the normal functioning of the bone marrow, leads to bone destruction and causes kidney failure.

Prevalence of the condition

The sponsor provided updated information on the prevalence of multiple myeloma based on data from the scientific literature and the EUCAN and NORDCAN databases.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of multiple myeloma 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 estimated to be approximately 3.3 people in 10,000. This is equivalent to a total of around 170,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, several medicines were authorised for multiple myeloma in the EU, including various medicines for cancer such as bortezomib, and immunomodulatory agents (thalidomide, lenalidomide and pomalidomide). They were usually combined with steroids to reduce the activity of the immune system, the body’s natural defences. Where these medicines did not work, some patients received an allogeneic stem-cell transplant (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow).

Significant benefit of Farydak

The COMP concluded that the claim of a significant benefit of Farydak in multiple myeloma is justified because Farydak has been shown to improve progression-free survival (how long the patients lived without their disease getting worse) of patients whose multiple myeloma had come back or got worse after previous treatments including bortezomib and immunomodulatory agents. These patients have limited treatment options and, therefore, a high unmet medical need.

The COMP conclusions are supported by data from a main study in multiple myeloma patients which showed that in those patients who had previously received at least two previous treatments, including bortezomib and an immunomodulatory medicine (such as thalidomide or lenalidomide), progression-free survival was 12.5 months with Farydak, versus about 5 months with placebo.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Farydak is of significant benefit to patients affected by multiple myeloma.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Farydak still meets the criteria for designation as an orphan medicinal product and that Farydak should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Novartis Europharm Limited
Frimley Business Park
Camberley GU16 7SR
United Kingdom
Tel. +41 61 324 11 11 (Switzerland)
E-mail: orphan.enquiries@novartis.com

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.