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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 , 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.

Source

1) Sacchetti M., Lambiase A., Diagnosis and management of neurotrophic keratitis. Clinical Ophthalmology 2014; 8: 571?579.

Notes:

Recombinant human Nerve Growth Factor (rhNGF), a molecule for ophthalmic use developed by Dompé, is the first potential targeted treatment for neurotrophic keratitis, a disease that lacks effective treatment and affects less than one in every 5,0001people.

rhNGF is the first clinical application of the research carried out by Rita Levi Montalcini (winner of the Nobel Prize for Medicine in 1986) on Nerve Growth Factor.

Preliminary results of the Phase I study confirm the tolerability of rhNGF and show a high percentage of patients achieved complete healing of corneal lesions.

rhNGF is now in Phase II development and patient enrolment is underway. The study is being carried out at 39 centres in 9 countries across Europe.

In the UK there are six centres of excellence involved in the trial: Moorfields Eye Hospital, London; Royal Victoria Infirmary, Newcastle; University Hospital Southampton; Birmingham and Midland Eye Centre; Manchester Royal Eye Hospital and Gartnavel General Hospital, Glasgow.

About rhNGF

rhNGF, the recombinant human Nerve Growth Factor developed by Dompé, is the same type of protein that is naturally produced by the body and that stimulates the growth, maintenance and survival of nerve cells, including those of the retina. rhNGF is currently in an advanced stage of clinical development for the treatment of neurotrophic keratitis; a rare corneal disease that affects less than 1 in every 5,000 people worldwide, as part of the REPARO international study. In animal studies, the drug proved effective in inhibiting the degeneration of the retina in different forms of retinitis pigmentosa. rhNGF could therefore integrate natural NGF in the clinic and improve the survival of retinal cells by slowing down the advancement of the disease and thus benefiting the maintenance of the visual capacity of patients.

The REPARO Study

The Phase I/II REPARO study is a randomised, double-blind, placebo-controlled trial combining single and repeated ascending dosage to assess the safety, tolerability and pharmacokinetics of recombinant human nerve growth factor (rhNGF) in eye drops, in adult patients affected by neurotrophic keratitis with corneal lesions of Grade 2 (persistent epithelial defect) or Grade 3 (corneal ulcer) of a moderate to severe degree. Only patients who have not responded to currently available medical treatments will be included in the study. The estimated treatment period is 8 weeks, with an observation period of 48 or 56 weeks. It is anticipated that patients will be enrolled at 39 sites in 9 different European countries.

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