EU/3/14/1299: Orphan designation for the treatment of systemic sclerosis

Systemic sclerosis is a complex disease in which the immune system (the body's natural defences) is overactive, causing inflammation and excess production of various proteins, particularly collagen. The reason why the immune system is overactive is not known. Collagen is an important component of connective tissue (the tissue that supports the skin and internal organs).

The overproduction of collagen leads to the abnormal growth of connective tissue, causing the skin to become thick and hard. It can also damage the blood vessel walls of the internal organs, such as the heart, lungs and kidneys. This makes it more difficult for the blood to move through the vessels, causing tissue damage, circulation problems and high blood pressure.

Systemic sclerosis is a long-lasting, debilitating disease and may be life threatening because of its possible effects on the gut, heart, lungs and kidneys.

At the time of designation, systemic sclerosis affected approximately 3.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 179,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of designation, there were no treatments for systemic sclerosis that could stop the build-up of collagen. Treatments authorised in the EU were aimed at relieving the symptoms of the disease and limiting the damage it causes. Several medicines were used to reduce inflammation and circulation problems. Bosentan was authorised in the EU specifically to treat patients with systemic sclerosis in whom poor blood circulation caused by the disease has led to the development of 'digital ulcers' (sores on the fingers and toes).

The sponsor has provided sufficient information to show that riociguat might be of significant benefit for patients with systemic sclerosis because early studies in experimental models show that it might be effective at reducing the abnormal growth of connective tissue, which is not targeted by existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Riociguat works by stimulating an enzyme called 'soluble guanylate cyclase', which regulates several processes, including the formation of connective tissue. By stimulating this enzyme, riociguat is expected to decrease the abnormal growth of fibrous connective tissue in patients with systemic sclerosis, thereby improving the symptoms of the disease.

The effects of riociguat have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with riociguat for the treatment of systemic sclerosis had been started.

At the time of submission, riociguat was authorised in EU as Adempas to increase exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH, where the blood vessels of the lungs are blocked or narrowed with blood clots) and pulmonary arterial hypertension (PAH, where the walls of the blood vessels of the lungs are thickened and the vessels become narrowed).

At the time of submission, riociguat was not authorised anywhere in the EU for systemic sclerosis 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 12 June 2014 recommending the granting of this designation.

• 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.