Neurotrophic keratitis: Preliminary data from the REPARO study
Dompé, an Italian biopharmaceutical company, is creating new prospects for the treatment of corneal ulcers in patients affected by neurotrophic keratitis, an untreatable rare eye condition that affects less than one in 5,000 people worldwide1.
rhNGF (recombinant human Nerve Growth Factor) is in clinical development in the REPARO study, which is being conducted at 39 centres in 9 European countries. Preliminary data from Phase I of the study, involving patients affected by moderate or severe neurotrophic keratitis, were presented at the ARVO Annual Meeting (Orlando, USA, 4-8 May 2014) and demonstrated that rhNGF is well tolerated.
The study examined 18 patients (7 men and 11 women) suffering from moderate or severe neurotrophic keratitis resulting from diabetes, eye infections caused by the herpes virus, infections, neurosurgical interventions and other related diseases. The patients enrolled in the study, who did not respond to currently available medical treatments, were divided into four groups. In the first group, patients were administered an eye drop solution for topical use at a dose of 10 µg/ml. In the second group, a simple vehicle was administered. In the third group, a dose of 20 µg/ml was given and, in the fourth group, a placebo was administered. At the end of the treatment, in addition to the results regarding tolerability and safety, 11 patients had a notable improvement in corneal conditions. Although the data are still "masked" and, therefore, it is not yet known which patients received rhNGF and which received the placebo, complete resolution of corneal lesions was recorded in the majority of patients, with similar percentages in the two groups treated with rhNGF at different doses, as well as an increase in corneal sensitivity in approximately one in every three patients.
"These results are of great importance in the course of the clinical development of rhNGF, a candidate drug that originates from the research carried out by Nobel Prize winner Rita Levi Montalcini," explains Eugenio Aringhieri, CEO of the Dompé Group. "Our researchers were the first to identify a biotech molecule of NGF for ophthalmic use. The results of this study highlight the potential of NGF in the field of ophthalmology. Dompé will continue pursuing its strong commitment towards patients, focusing its R&D in areas characterised with high unmet medical needs, such as neurotrophic keratitis."
NGF is a protein that stimulates the growth, maintenance and survival of neurons. The world of research has, over time, formulated the hypothesis of the efficacy of the topical use of NGF, given that neurotrophic keratitis is a neurodegenerative disease. It is a known fact that the integrity of the cornea - by far the most innervated organ of the human body (nearly 400 times more than the skin) - is maintained by innervation rather than vascularity. The research conducted by the Dompé Group has made it possible to continue the studies in a clinical setting, ensuring the biotechnological production of an rhNGF-based treatment that has the potential to provide patients suffering from neurotrophic keratitis with a true and effective therapeutic response.
"Neurotrophic keratitis is characterised by severity and a degenerative course, resulting from reduced innervation of the cornea as a result of various disease states (for example, diabetes, herpes lesions, surgical interventions) that can even lead to disabling consequences, such as ulceration and perforation of the cornea resulting in loss of visual functions," explains Professor Stefano Bonini, Head of the Department of Ophthalmology at the BioMedico Campus of Rome and Principal Investigator of the REPARO Study. "Today, after years of study, we are particularly proud to be able to substantiate our research, which is also confirmed by the promising results of the REPARO Study. An encouraging result has also come from the industrial sector which, through expertise and vision, has made it possible to produce a drug under clinical evaluation within a very short time."
The molecule is also under experimentation for the treatment of dry eye syndrome and Retinitis Pigmentosa.