EU/3/11/909

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Orphan designation

On 27 September 2011, orphan designation (EU/3/11/909) was granted by the European Commission to Actelion Registration Limited, United Kingdom, for macitentan for the treatment of pulmonary arterial hypertension.

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

What is pulmonary arterial hypertension?

Pulmonary arterial hypertension is a condition where there is high blood pressure in the arteries that supply the lungs. In patients with pulmonary arterial hypertension, there is a thickening of the muscles in the walls of the arteries and a narrowing of the arteries in the lungs, making it harder for blood to flow to the lungs. Pulmonary arterial hypertension is a long-term debilitating and life-threatening condition that shortens patients’ life expectancy because it may lead to heart failure and difficulty breathing.

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

At the time of designation, pulmonary arterial hypertension affected less than 1.8 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 91,000 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 507,700,000 (Eurostat 2011).

What treatments are available?

Several medicines were authorised for the treatment of pulmonary arterial hypertension in the EU at the time of designation. They included bosentan, ambrisentan, tadalafil, sildenafil, iloprost, epoprostenol, and treprostinil sodium. Surgery was also used in some patients to carry out a lung transplant or atrial septostomy (where a small hole is created between the upper two chambers of the heart, the atria).

The sponsor has provided sufficient information to show that macitentan might be of significant benefit for patients with pulmonary arterial hypertension because it may penetrate the diseased tissue more effectively than current treatments with a similar mechanism of action, which may improve the outcome of patients with pulmonary arterial hypertension, particularly when used in combination with 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?

Macitentan is expected to work as an ‘endothelin receptor antagonist’. This means that it is expected to block the receptors (type A and B) which the substance called ‘endothelin-1’ normally attaches to and activates. Endothelin is a naturally occurring substance that is released from lining of the blood vessels. It is present at raised levels in patients with pulmonary arterial hypertension, causing the blood vessels to constrict and the blood vessel walls to thicken. By blocking endothelin receptors , macitentan is expected to stop endothelin from constricting the blood vessels, thereby leading to a decrease in the blood pressure and a reduction of the symptoms of pulmonary arterial hypertension.

What is the stage of development of this medicine?

The effects of macitentan have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with macitentan in patients with pulmonary arterial hypertension were ongoing.

At the time of submission, macitentan was not authorised anywhere in the EU for pulmonary arterial hypertension. Orphan designation of macitentan had been granted in the United States for the treatment of pulmonary arterial hypertension.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 July 2011 recommending the granting of this designation.

Update: Macitentan (Opsumit) has been authorised in the EU since 20 December 2013. Opsumit, as monotherapy or in combination, is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III.

Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease

More information on Opsumit can be found in the European public assessment report (EPAR).

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>Macitentan</p>
Active substanceMacitentan
Medicine NameOpsumit
Disease/conditionTreatment of pulmonary arterial hypertension
Date of decision27/09/2011
OutcomePositive
Orphan decision numberEU/3/11/909

Review of designation

During its meeting of 5-6 November 2013, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/11/909 for Opsumit (macitentan) as an orphan medicinal product for the treatment of pulmonary arterial hypertension. 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 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.

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

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Opsumit, as monotherapy or in combination, for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of pulmonary arterial hypertension (PAH)’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2011. PAH remains a long-term debilitating and life-threatening condition that shortens patients’ life expectancy because it leads to heart failure and difficulty in breathing that worsens over time.

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 PAH 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 less than 1.8 people in 10,000. This is equivalent to a total of less than 92,000 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 for the treatment of pulmonary arterial hypertension in the EU. They included ambrisentan, bosentan, epoprostenol, iloprost, sildenafil, tadalafil, and treprostinil.

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Opsumit in the treatment of PAH is justified on the basis of data from a main clinical study in 742 patients. The study showed a reduction of PAH-related illness (including serious heart and lung problems or worsening of PAH symptoms) and of death in patients already treated with currently authorised treatments.

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

Conclusions

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

Related information

Sponsor’s contact details

Actelion Registration Limited
BSI Building 13th floor
389 Chiswick High Road
London W4 4AL
United Kingdom
Tel. + 44 (0)20 8987 3320
Fax + 44 (0)20 8987 3322
E-mail: registration@actelion.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.