EU/3/16/1704: Orphan designation for the treatment of sporadic lymphangioleiomyomatosis

Lymphangioleiomyomatosis is a disease that affects mostly women and is caused by the spread of immature muscle-like cells (known as LAM cells) to the lungs, lymph nodes and the kidneys. Patients with lymphangioleiomyomatosis often have problems with breathing, accumulation of fluid in the chest and abdomen (belly), and masses in the abdomen, which can cause bleeding. The sporadic form of lymphangioleiomyomatosis has more severe effects on breathing.

Sporadic lymphangioleiomyomatosis is life-threatening and debilitating in the long term because of worsening lung function and other lung problems, as well as bleeding and complications arising from the presence of masses in the abdomen and pelvis.

At the time of designation, sporadic lymphangioleiomyomatosis affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 513,700,000 (Eurostat 2016).

At the time of the orphan designation, no satisfactory methods of treatment were authorised for sporadic lymphangioleiomyomatosis. Treatment for severe symptoms of the disease included surgery and lung transplantation.

Sirolimus blocks the activity of mTOR, a protein involved in the proliferation of LAM cells. By blocking mTOR, the medicine is expected to reduce the number of LAM cells in the lungs, thereby helping to relieve patients' symptoms.

The effects of sirolimus have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with sirolimus in patients with sporadic lymphangioleiomyomatosis were ongoing.

At the time of submission, sirolimus was authorised in the EU for preventing rejection of transplanted kidneys. Oral (by mouth) sirolimus has also been authorised in the United States for the treatment of lymphangioleiomyomatosis.

At the time of submission, sirolimus was not authorised anywhere in the EU for sporadic lymphangioleiomyomatosis. Orphan designation had been granted in the United States for sirolimus for the treatment of lymphangioleiomyomatosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 16 June 2016 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.