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Orphan designation

On 22 February 2018, orphan designation (EU/3/18/1982) was granted by the European Commission to ATXA Therapeutics Limited, Ireland, for N-(tert-butylcarbamoyl)-5-cyano-2-((4'-(difluoromethoxy)-[1,1'-biphenyl]-3-yl)oxy)benzenesulfonamide (also known as NTP42) for the treatment of pulmonary arterial hypertension.

What is of pulmonary arterial hypertension?

Pulmonary arterial hypertension is a condition in which patients have abnormally high blood pressure in the arteries in the lungs. In pulmonary arterial hypertension, the muscles in the walls of the arteries in the lungs become thicker and the arteries become narrower and less elastic, 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 difficulty breathing and heart failure.

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

At the time of designation, pulmonary arterial hypertension affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 103,000 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 517,400,000 (Eurostat 2018).

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 ambrisentan, bosentan, epoprostenol, iloprost, macitentan, riociguat, selexipag, sildenafil, tadalafil and treprostinil. Lung transplantation or atrial septostomy (where a small hole is created between the atria, the upper two chambers of the heart) were also used in some patients.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with pulmonary arterial hypertension because laboratory studies showed that the medicine, given in combination with sildenafil, was more effective at reducing blood pressure than sildenafil 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?

The medicine blocks the action of a substance in the body called thromboxane. Thromboxane is involved in pulmonary hypertension by causing blood vessels to narrow. Patients with pulmonary arterial hypertension have too much thromboxane and by blocking the receptors to which thromboxane normally attaches, the medicine is expected to reduce hypertension.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with pulmonary arterial hypertension had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for pulmonary arterial hypertension 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 18 January 2018 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>N-(tert-butylcarbamoyl)-5-cyano-2-((4'-(difluoromethoxy)-[1,1'-biphenyl]-3-yl)oxy)benzenesulfonamide</p>
Active substanceN-(tert-butylcarbamoyl)-5-cyano-2-((4'-(difluoromethoxy)-[1,1'-biphenyl]-3-yl)oxy)benzenesulfonamide
Medicine Name
Disease/conditionTreatment of pulmonary arterial hypertension
Date of decision22/02/2018
Orphan decision numberEU/3/18/1982

Review of designation

Sponsor’s contact details

ATXA Therapeutics Limited
75 Avoca Park, Avoca Avenue
Co. Dublin
A94 N803 Ireland
Tel. +353 877765446

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.