EU/3/15/1447

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Orphan designation

On 12 February 2015, orphan designation (EU/3/15/1447) was granted by the European Commission to Elli Lilly Nederland B.V., the Netherlands, for olaratumab for the treatment of soft tissue sarcoma.

Olaratumab has been authorised in the EU as Lartruvo since 9 November 2016.

What is soft tissue sarcoma?

Soft tissue sarcoma is a type of cancer that affects the soft, supportive tissues of the body. It can occur in muscles, blood vessels, fat tissue or in other tissues that support, surround and protect organs. Patients with soft tissue sarcoma do not usually have symptoms in the early stages of the disease. First symptoms appear when the tumour grows large enough to cause swelling and pain.

Soft tissue sarcoma is a long-term debilitating and life-threatening disease, particularly when the cancer has spread to other parts of the body.

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

At the time of designation, soft tissue sarcoma affected not more than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 154,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, the main treatment for early-stage soft tissue sarcoma was surgery. For large sarcomas, surgery was usually followed by radiotherapy (treatment with radiation) and chemotherapy (medicines to treat cancer) to kill any cancerous cells that were left behind. Several medicines were authorised in the EU for the treatment of soft tissue sarcoma including doxorubicin.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with soft tissue sarcoma because early studies indicate that it might improve the outcome of patients when combined with doxorubicin. 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?

Olaratumab is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a protein called platelet-derived growth factor receptor alpha (PDGFRα). This protein is often found on the surface of cells where it is thought to play a role in regulating cell multiplication. In cancers such as soft tissue sarcoma these proteins are present in high levels or overactive, causing cells to become cancerous. When olaratumab attaches to PDGFRα on sarcoma cells, it is expected to block its activity, thereby slowing down the growth of the cancer.

What is the stage of development of this medicine?

The effects of olaratumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with olaratumab in patients with soft tissue sarcoma were ongoing.

At the time of submission, olaratumab was not authorised anywhere in the EU for soft tissue sarcoma. Orphan designation of olaratumab had been granted in the United States of America for the treatment of soft tissue sarcoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 January 2015 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.

Key facts

Product details for <p>Olaratumab</p>
Active substanceOlaratumab
Medicine NameLartruvo
Disease/conditionTreatment of soft tissue sarcoma
Date of decision12/02/2015
OutcomePositive
Orphan decision numberEU/3/15/1447

Review of designation

During its meeting of 4-6 October 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/15/1447 for Lartruvo (olaratumab) as an orphan medicinal product for the treatment of soft tissue sarcoma. 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 soft tissue sarcoma. 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 the same 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 Lartruvo with the following indication: ‘in combination with doxorubicin for the treatment of adult patients with advanced soft tissue sarcoma who are not amenable to curative treatment with surgery or radiotherapy and who have not been previously treated with doxorubicin’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of soft tissue sarcoma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2015. Soft tissue sarcoma remains a long-term debilitating and life-threatening disease, particularly when the cancer has spread to other parts of the body.

Prevalence of the condition

The sponsor provided updated information on the prevalence of soft tissue sarcoma based on data from cancer registries and the published scientific literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of soft tissue sarcoma 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 people in 10,000. This is equivalent to a total of around 154,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of soft tissue sarcoma. These include the cancer medicines cyclophosphamide, dacarbazine, doxorubicin, epirubicin, ifosfamide and melphalan.

Significant benefit of Lartruvo

The COMP concluded that the claim of a significant benefit of Lartruvo over doxorubicin is justified, because Lartruvo plus doxorubicin was more effective than doxorubicin alone at prolonging the time patients live without their disease getting worse. Furthermore, patients treated with Lartruvo plus doxorubicin survived 26.5 months on average compared with 14.7 months in patients treated with doxorubicin only. As no other standard treatment has been shown to produce similar improvements in survival, the COMP considered that these results also demonstrated significant benefit over other authorised treatments.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Lartruvo is of significant benefit to patients affected by soft tissue sarcoma.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Lartruvo still meets the criteria for designation as an orphan medicinal product and that Lartruvo should remain in the Community Register of Orphan Medicinal Products. More information on the COMP assessment can be found in the October 2016 COMP minutes.

Sponsor’s contact details

Eli Lilly Nederland B.V.
Papendorpseweg 83
Utrecht 3528 BJ
The Netherlands
Tel. +31 30 60 25 800
Fax +31 30 60 25 888
E-mail: eu_orphan@lilly.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.