The Company has agreed with the U.S. Food and Drug Administration (FDA) on plans for the Phase III clinical program, which is designed to support the submission of a New Drug Application (NDA). The Company has received final, End-of-Phase II meeting minutes from the FDA. SYL1001 is an advance in the development of innovative compounds in different therapeutic fields, through the novel technology of gene silencing, based on RNA interference (RNAi). In the HELIX study, more than 30 centers from 5 European countries, including Spain, will participate with the objective of evaluating the effect of the ophthalmological solution SYL1001 for improvements in the signs and symptoms of dry eye syndrome in about 300 patients an area in which few therapeutic options exist today. SYL1001 is a compound based on RNAi being administered in the form of eye drops that block the synthesis of a receptor implicated in the pathology of dry eye syndrome.
In Spain it is estimated that 1 in 5 people that visit the ophthalmologist do it for this reason. Patients with dry-eye syndrome suffer the chronic loss of lubrication and hydration on the ocular surface. More than 5 million people in Spain suffer from this condition -this is between 10% and 20% of the population-1,2, mainly women over 40 years of age. The risk of developing this disorder increases in 35% every decade thereafter2. Around the world, 344 million people suffer from this syndrome.
Dry eye syndrome is characteristic in people that live in developed countries and is caused by pollution, air conditioning, the use of contact lenses, refractive eye surgery or the continued use of computers. The most common symptoms of this pathology are burning, a constant itching, eye fatigue, dryness, blurred vision, the sensation of having a foreign body or eye pain , are some of the symptoms.
As explained by Dr Ana Isabel Jimenez, COO and Director of R&D at Sylentis, "the RNA interference on which we are working, could improve the signs and symptoms for patients that suffer from this syndrome, given that this compound could reduce the inflammatory parameters of the eye´s surface, could improve the quality of the tear and could reduce the ocular pain associated with dry eye syndrome. We consider that our molecule SYL1001 could be a very effective and important therapeutic alternative for these patients".
The Company is working on the investigation of new treatments for ophthalmological and inflammatory illnesses. "Up to today, the line of work in which we have more rapidly advanced in is in ophthalmology, for the treatment of illnesses such as dry eye syndrome, glaucoma, ocular allergies and illnesses of the retina", added Dr Jimenez.
What is RNA interference?
RNA interference is an innovative technology that looks for a reduction in the anomalous production of protein, silencing the RNA Messenger. The RNAi provides a great step forward, as it provides a new mechanism of action to confront numerous pathologies . Nowadays there are two marketed products based on this technology and there are several drugs in different phases of clinical development. Pathologies, such as dry eye syndrome, are produced by an alteration in certain proteins. Through this technology, the production of proteins that take part in various pathologies could be decreased or very specifically controlled .
"This is very promising as a new treatment for eye illnesses because it permits confronting the illness with a novel mechanism of action. Moreover, in all the clinical studies in which we have participated, the efficacy of SYL1001 has been demonstrated in patients, along with a high tolerance and safety to the ocular surface", explained Dr Jose Manuel Benítez del Castillo Sánchez, professor of ophthalmology and section head at the Clinical Hospital San Carlos' ocular surface and inflammation unit in Madrid.
The compounds based on RNAi usually have a prolonged effect in comparison with traditional drugs. "This drug is particularly interesting in chronic diseases and areas in which patient compliance is a challenge because it may show an increased duration of effect", said Dr Benitez del Castillo.
Spain leads the HELIX study
With the purpose of progressing in this field, Sylentis has begun the multicenter, random, controlled and double blind Phase III clinical trial in more than 30 hospitals in Spain, Germany, Estonia, Portugal and Italy. The trial, in which 300 patients are going to be enrolled, and begins with one Spanish patient, will evaluate the efficacy of the product patented by Sylentis, SYL1001, in the treatment of the signs and symptoms of dry eye disease .
"Nowadays that, with the knowledge obtained, we have an opportunity to develop therapies based on RNAi", concluded Dr Benitez del Castillo. "The challenge now is to transform this powerful technology into marketable products".
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For more information about the clinical trial: https://clinicaltrials.gov/ct2/show/NCT03108664?term=SYL1001&rank=2
Bibliography
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The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf, 2007. 5(2): p. 75-92
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Soutschek J1, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, Elbashir S, Geick A, Hadwiger P, Harborth J, John M, Kesavan V, Lavine G, Pandey RK, Racie T, Rajeev KG, Röhl J, Toudjarska I, Wang G, Wuschko S, Bumcrot D, Koteliansky V, Limmer S, Manoharan M, Vornlocher HP. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature. 2004 Nov 11;432(7014):173-8
Moreno-Montañes J, Sádaba B, Ruz V, Gomez-Guiu A, Zarranz J, Gonzalez MV, Pañeda C, Jimenez AI. Phase I Clinical Trial of SYL040012, A Small Interfering RNA Targeting β-Adrenergic Receptor 2, for Lowering Intraocular Pressure. Mol Ther. 2014, 22(1):226-32
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