June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Clinical and preclinical study correlation for SYL1001, a new treatment for dry eye disease
Author Affiliations & Notes
  • Victoria Gonzalez
    Clinical, Sylentis, Tres Cantos (Madrid), Spain
  • Veronica Ruz
    Regulatory affairs, Sylentis, Tres Cantos (Madrid), Spain
  • Covadonga Pañeda
    R&D, Sylentis, Tres Cantos (Madrid), madrid, Spain
  • Anne-Marie Bleau
    Clinical, Sylentis, Tres Cantos (Madrid), Spain
  • Beatriz Vargas
    Regulatory affairs, Sylentis, Tres Cantos (Madrid), Spain
  • Ana Isabel Jimenez
    R&D, Sylentis, Tres Cantos (Madrid), madrid, Spain
  • Footnotes
    Commercial Relationships   Victoria Gonzalez, Sylentis (E); Veronica Ruz, Sylentis (E); Covadonga Pañeda, Sylentis (E); Anne-Marie Bleau, Sylentis (E); Beatriz Vargas, Sylentis (E); Ana Isabel Jimenez, Sylentis (E)
  • Footnotes
    Support  IPT-2012-0438-010000 INNPACTO
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2670. doi:
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      Victoria Gonzalez, Veronica Ruz, Covadonga Pañeda, Anne-Marie Bleau, Beatriz Vargas, Ana Isabel Jimenez; Clinical and preclinical study correlation for SYL1001, a new treatment for dry eye disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2670.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Correlate the results of SYL1001 animal biodistribution studies to phase I and phase II clinical results in patients with Dry eye disease (DED)

Methods : Sylentis is developing a new product based on RNA interference, SYL1001 eye drops, to treat signs and symptoms of DED. Biodistribution studies were carried out in New Zealand white rabbits. Samples of ciliary body (CB), iris (I), lacrimal gland (LG), trigeminal ganglion (TG), cornea (C), aqueous humour (AH), vitreous humour (VH), systemic tissues and plasma were collected 5 and 30 minutes after instillation of 4 different doses (0.375%, 0.75%, 1.125% and 1.5%) of SYL1001. These doses were assessed in phase I (NCT01438281, EudraCT No: 2010-023113-56) and two phase 2 trials (NCT01776658, EudraCT No: 2012-001177-93 & NCT02455999, EudraCT No: 2014-004857-15). Correlations of preclinical and clinical studies were carried out to determine the optimum dose.

Results : Results in animal studies showed that SYL1001 is efficiently taken up by the cells of the ocular tissues and only trace levels of the product are detected in plasma and systemic tissues. These studies demonstrated that absorption of SYL1001 is dose-dependent up to the dose of 1.125%. Concentrations above 1.125% resulted in lower amounts of SYL1001, most likely due to saturation of the mechanisms of entrance.
In phase I trial, 30 subjects were treated with SYL1001 eye drops and no drug-related adverse events were reported. This result correlates nicely with the absence of product in plasma after instillation of SYL1001. In Phase II trials, 127 patients were randomized into five arms (0.375%, 0.75%, 1.125% and 2.25% of SYL1001 and placebo (vehicle) q.d). The dose of 1.125% was significant better than the other doses and placebo (p=0.016) in the treatment of patients with DED in terms of reducing the ocular pain/discomfort (VAS scale), corneal staining and hyperemia

Conclusions : SYL1001 is a product based on RNA interference being developed to treat signs and symptoms of DED. Finding the optimum dose is critical to guarantee the successful development of these therapies. Animal studies showed that the dose of 1.125% was able to achieve the highest concentration at the site of action whereas only trace levels of product were detected systemically. Clinical studies verified that this dose was the most efficacious drug for the treatment of DED with very low incidence of adverse events.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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