EU/3/15/1586: Orphan designation for the treatment of neurotrophic keratitis

Neurotrophic keratitis is a condition of the cornea (the clear layer at the front of the eye) caused by damage to the trigeminal nerve, the nerve that allows the surface of the eye to feel things and which supplies growth factors and other substances needed for normal growth and repair of the eye's surface. The nerve damage results in a lack of sensitivity in the cornea, and to dryness, ulceration and scarring that interferes with vision.

Neurotrophic keratitis is a long-lasting and debilitating condition due to damage to the cornea and possible loss of sight.

At the time of designation, neurotrophic keratitis affected approximately 4.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 215,000 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 512,900,000 (Eurostat 2015).

No satisfactory methods were authorised for the treatment of neurotrophic keratitis in the EU at the time of designation. Management depended on the stage of the disease and included supportive measures such as eye drops to moisten and lubricate the eye, antibiotics for eye infections, and the use of protective contact lenses, as well as surgery where appropriate.

Patients with neurotrophic keratitis have lower than normal levels of growth factors that are normally supplied by the trigeminal nerve and which play an important role in the growth and survival of the cells of the cornea. The medicine is a copy of a human growth factor called nerve growth factor. When given as eye drops to patients with neurotrophic keratitis, the medicine is expected to help restore some of the normal healing processes in the eye and repair the damages to the cornea associated with the condition.

The medicine is produced by a method known as 'recombinant DNA technology': it is made by bacteria into which a gene (DNA) has been introduced that enables the bacteria to produce human nerve growth factor.

The effects of recombinant human nerve growth factor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with recombinant human nerve growth factor in patients with neurotrophic keratitis were ongoing.

At the time of submission, recombinant human nerve growth factor was not authorised anywhere in the EU for neurotrophic keratitis. Orphan designation of the medicine had been granted in the United States for neurotrophic keratitis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 November 2015 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.