Sylentis, a pharmaceutical company in the PharmaMar Group (MSE:PHM) and a pioneer in the research and development of new drugs based on gene silencing (interference RNA, RNAi), has presented the results of two Phase II dose-finding and efficacy assessment clinical trials (SYL1001_II and SYL1001_III) with the investigational medicinal product SYL1001 for treating ocular discomfort related to dry eye syndrome.
These randomised parallel group, double-masked and placebo controlled Phase II trials took place at 8 centres in two European countries: Spain and Estonia. A total of 127 patients with ocular pain related to dry eye syndrome took part in the trials, which assessed safety and efficacy of four doses of SYL1001 (0.375%, 0.75%, 1.125% and 2.25%) against placebo following 10 days of once-per-day administration in the form of eye drops.
The results revealed that 1.125% was an optimal dose which achieved the best primary and secondary endpoints, reducing not only ocular pain but also conjunctival hyperaemia related to dry eye syndrome.
The two trials also confirmed a favourable safety and tolerance profile of SYL1001, previously observed in Phase I trial, with no differences in the percentage of adverse events between the assessed doses of SYL1001 and placebo group.
"These positive results support continuing clinical development of SYL1001. Sylentis is currently designing the Phase III clinical program which it will be validated with the relevant regulatory authorities," said Dr Ana Isabel Jiménez, COO of Sylentis.
The results and additional analysis of these clinical trials will be presented at the ARVO conference in May 2016.
About the SYL1001_II (NCT01776658) and SYL1001_III (NCT02455999) trials
SYL1001_II/III are dose-finding, multi-centre randomised parallel-group double-masked placebo-controlled Phase II clinical trials to evaluate the efficacy and safety of SYL1001 in patients with ocular pain related to dry eye syndrome after ten days of treatment (one drop per day in each eye).
SYL1001_II included 61 patients at 5 centres in Spain, divided into three groups of 20 patients each, who received SYL1001 (1.125% or 2.25%) or placebo. SYL1001_III included 66 patients at 5 centres in Spain and Estonia, divided into three groups of approximately 22 patients each and treated with SYL1001 (0.375% or 0.75%) or placebo.
Primary endpoints evaluated were dry eye symptoms using OSDI (Ocular Surface Disease Index) and VAS (Visual Analogue Scale), and signs associated with this pathology (conjunctival hyperaemia and corneal fluorescence staining) after ten days of treatment.
Secondary endpoints included assessment of vital signs, blood and urine analysis, and alteration of ocular parameters (IOP, TBUT, Schirmer test, visual acuity, and assessment of the anterior segment) together with the appearance of adverse events as a measure of tolerance.
SYL1001 is a drug based on RNAi that is administered as preservative-free eye drops; it selectively inhibits production of the TRPV1 receptor. These receptors are ion channels that mediate the transmission of ocular pain. SYL1001 is a small synthetic double-stranded RNA oligonucleotide (siRNA) with a novel and highly selective mechanism of action. Non-clinical studies conducted by Sylentis with SYL1001 have demonstrated it has high ability to inhibit this specific target and block the perception of ocular pain in animals . SYL1001 is a product undergoing development for the treatment or prevention of ocular pain related to with dry eye syndrome, and has potential to be developed for other pathologies that cause ocular pain (corneal lesions, refractive surgery, etc.).
About RNA interference (RNAi)
RNA interference (RNAi) is a natural cellular process that regulates the expression of certain genes, providing a role in innate defense and development in animal and plants. This process is used to specifically silence genetic transcripts that encode protein-causing diseases. The therapeutic application of targeted siRNAs is booming given the specificity of gene silencing for a particular protein in a given tissue and the lack of side effects. This new approach to drug discovery is a promising technology that is rapidly moving in the translational research space .
About dry eye syndrome
Dry eye syndrome is a multifactorial disease of the tear film and ocular surface that produces symptoms of ocular discomfort, eyesight disorders, and tear film instability with potential damage to the ocular surface. Dry eye syndrome is accompanied by such symptoms as ocular pain, itching, stinging, and irritation of the eye tissues. It is a characteristic disease of developed countries, associated with pollution, air conditioning, the use of contact lenses, refractive surgery and continued use of computers. Moreover, the amount and quality of tears decrease with age. Prevalence is between 5% and 30% among people aged 50 or over, and it is more frequent in women .
Dry eye can be treated with cyclosporin drops or autologous serum, but there is as yet no specific product for chronic treatment of the ocular pain related to dry eye syndrome; oral analgaesics or anaesthetics are used in general. However, the main treatment consists of artificial tears, in the form of drops, gel or creams. Preservative-free eye drops have generally been found to offer the best long-term response.