EU/3/12/1076

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Orphan designation

Please note that this product (marketed as Empliciti) was withdrawn from the Community Register of designated Orphan Medicinal Products by the European Commission in April 2016, at the time of the granting of a marketing authorisation.

Update: elotuzumab has been authorised in the EU as Empliciti since 11 May 2016.

On 6 December 2012, orphan designation (EU/3/12/1076) was granted by the European Commission to Pharmathen SA, Greece, for allopurinol sodium for the treatment of perinatal asphyxia.

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

What is perinatal asphyxia?

Perinatal asphyxia happens when babies are born without enough oxygen in their blood. This is generally due to interruptions of the oxygen supplied by the mother through the placenta or the umbilical cord. Perinatal asphyxia can cause damage to the brain and other organs.

Perinatal asphyxia is a long-term debilitating disease because it can lead to the child being severely handicapped, with mental retardation and physical disabilities. It is also life-threatening, as up to a fifth of the babies with the condition will die within the first days after birth.

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

At the time of designation, perinatal asphyxia affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to around 36,000 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 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of orphan designation, there was no treatment for perinatal asphyxia authorised in the EU. Babies with perinatal asphyxia received supportive treatment, and they were sometimes cooled down to a body temperature lower than normal (hypothermia) for 12 to 72 hours after birth to reduce the extent of the damage caused by the asphyxia.

How is this medicine expected to work?

Allopurinol has been used for many years as tablets in the treatment of gout. It works by blocking an enzyme called xanthine oxidase, which plays an important part in converting substances in the body called purines into another substance, uric acid. The action of xanthine oxidase is thought to contribute to the damage in perinatal asphyxia. In addition, allopurinol seems to increase the amount of other substances that help protect brain cells from damage. For the treatment of perinatal asphyxia, allopurinol sodium is expected to be given by injection.

What is the stage of development of this medicine?

The effects of allopurinol sodium have been evaluated in experimental models.

At the time of submission of the application for orphan designation, preliminary clinical trials with allopurinol sodium in patients with perinatal asphyxia had finished. 

At the time of submission, allopurinol sodium was not authorised anywhere in the EU for perinatal asphyxia 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 7 November 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/3/12/1037: Public summary of opinion on orphan designation: Elotuzumab for the treatment of multiple myeloma (English only) 26/09/2012 23/05/2016

Key facts

Product details for <p>Allopurinol sodium</p>
Active substanceAllopurinol sodium
Medicine Name
Disease/conditionTreatment of perinatal asphyxia
Date of decision06/12/2012
OutcomeWithdrawn
Orphan decision numberEU/3/12/1076

Review of designation

On 8 April 2016, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/12/1037 of Empliciti (elotuzumab) as an orphan medicinal product for the treatment of multiple 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 concluded that one of the criteria for orphan designation was no longer met and therefore recommended that the orphan designation of the product should not be maintained1.


1The removal of the orphan designation at time of marketing authorisation means that the product cannot benefit from 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication can be placed on the market.

Life-threatening or chronically debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Empliciti with the following indication:

‘Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.’

This indication falls within the scope of the product’s designated orphan indication, which is ‘treatment of 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 condition that is debilitating in the long term and life threatening, particularly 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 GLOBOCAN 2012, an international web portal for cancer research.

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 less than 4 people in 10,000. This is equivalent to a total of fewer than 205,000 people in the EU.

Existence of other methods of treatments

At the time of the review of the orphan designation, bortezomib, carfilzomib, doxorubicin and lenalidomide were authorised in the EU for the treatment of patients with multiple myeloma who had received at least one previous treatment (‘second-line therapy’). Carfilzomib, an orphan medicine, was the most recent to have received marketing authorisation.

Significant benefit of Empliciti

The COMP concluded that the claim of a significant benefit of Empliciti in multiple myeloma is no longer justified. In indirect comparisons between Empliciti and carfilzomib, 2-year survival was similar with both treatments (at around 73%) and overall survival did not appear to be greater with Empliciti. In addition, analyses of outcomes in different subgroups of patients did not conclusively show a better efficacy or safety with Empliciti.

Therefore, the COMP concluded that Empliciti did not meet the criteria for significant benefit assumed at the time of the original orphan designation.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP concluded that Empliciti no longer meets one of the criteria for designation as an orphan medicinal product. Therefore, the COMP recommended that the product should be removed from the Community Register of Orphan Medicinal Products.

Sponsor’s contact details

Pharmathen S.A.
Monumental Plaza Building A
44 Kifisias Avenue
151 25 Marousi
Attiki
Greece
Tel. +30 210 6604493
Fax +30 210 6604583
E-mail: dantoniadis@pharmathen.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.