Dompé’s investigational biotech molecule receives orphan drug designation for treatment of neurotrophic keratitis

Dec 8 2015

The Dompé biopharmaceutical company announced today that the Committee for Orphan Medicinal Products of the European Medicines Agency (EMA) has officially designated recombinant human Nerve Growth Factor (rhNGF) - the investigational biotech molecule developed by Dompé based on research by Nobel Laureate Rita Levi Montalcini - as an orphan drug for the treatment of neurotrophic keratitis. NGF is the first neurotrophic factor to be identified and purified, and represents one of the most interesting topics being studied in medicine today and specifically in ophthalmology.

Orphan drug designation represents a milestone in the development of NGF in eye pathologies. After the first studies were conducted with murine NGF, the molecule's potential was further investigated by the Dompé Group, which has developed a process for the production of recombinant human NGF on an industrial scale at the biotechnology plant in L'Aquila, Italy. The development of an rhNGF-based biotech eye drops solution marked the beginning of a research effort to evaluate the safety and efficacy of the investigational drug in patients with neurotrophic keratitis, a rare and orphan disease.

The cornea can be described as a "transparent window", playing an essential role in the passage of visual stimuli to the retina of the eye; innervation is particularly high in the cornea relative to other parts of the eye. This characteristic was the starting point that allowed Dompé to adopt this innovative approach. The mechanism of action of rhNGF aims to restore innervation in the corneal area, which may have been damaged due to various pathological causes (surgery, herpetic infections, trauma, burns, etc.) capable of resulting in neurotrophic keratitis. The goal of treatment is to restore corneal integrity and, consequently, to recover visual function.

The scientific community is waiting for the results of the REPARO Phase I/II clinical trial, the first international trial to test the efficacy and safety of rhNGF for ophthalmic use in patients affected by the disease. This randomized, double-blind, vehicle-controlled parallel group study was conducted in 39 centres in nine European countries, and enrolled adult patients with unilateral neurotrophic keratitis with corneal lesions of stage 2 (persistent epithelial defect) or stage 3 (corneal ulcer) who did not respond to currently available medical treatments. The final results are expected in the coming months.

“Orphan drug designation by EMA for rhNGF fills Dompé with great pride and will encourage us to continue in our commitment to provide innovative solutions to the unmet needs of Patients in ophthalmology,” says Eugenio Aringhieri, Dompé Chief Executive Officer. “European recognition follows that of the Food and Drug Administration, which granted rhNGF orphan drug designation for the treatment of neurotrophic keratitis and allowed the activation of an Investigational New Drug application for the start of a clinical trial in the United States. Pending the results of the REPARO trial, our work is constantly projected toward making this therapeutic option available, thus allowing physicians and Patients alike to have a potential innovative approach targeted to this pathology for which there is currently no treatment. In the future, rhNGF may provide new research opportunities including in Patients with other eye diseases, especially those affecting the posterior segment of the eyeball. I'm referring here to more common diseases that can lead to loss of sight, such as glaucoma, or rare forms of congenital retinal degeneration, such as retinitis pigmentosa, for which rhNGF has already received orphan drug designation in Europe and the US."

rhNGF

rhNGF, the recombinant human Nerve Growth Factor developed by Dompé, is a protein that is naturally produced by the body and promotes the development and survival of nerve cells, including those of the retina. NGF (Nerve Growth Factor) was discovered by Rita Levi Montalcini, who was awarded the Nobel Prize in Physiology or Medicine in 1986. NGF stimulates the growth, maintenance, and survival of nerve cells in the cornea. (Levi Montalcini R., The nerve growth factor 35 years later, Science 1987). The cornea has particularly dense innervation, approximately 400 times denser than that of the skin. The rhNGF-based eye drops solution is currently being studied in patients with neurotrophic keratitis. Due to its innovative mechanism of action, rhNGF may be the subject of future studies in patients with other forms of optic neuropathies, such as retinitis pigmentosa, glaucoma, and dry eye syndrome. rhNGF for ophthalmic use has not been registered yet for any indication in any country.

Neurotrophic keratitis

Neurotrophic keratitis is a rare serious degenerative disease of the eye for which there still is no treatment, characterized by progressive damage to the cornea that can lead to corneal perforation, with consequent loss of vision. It can be caused by various clinical ocular conditions such as herpetic corneal infections (herpes zoster and simplex), eye surgery, misuse of topical medications, use of contact lenses, and even systemic conditions such as diabetes or vitamin A deficiency. Considering all its forms, it affects less than 1 in 2,000 people in the world. Neurotrophic keratitis is unilateral in most cases, but it frequently occurs in both eyes.