June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Comparison of a Novel Janus Kinase Inhibitor to Available Treatments in a Murine Model of Meibomian Gland Dysfunction
Author Affiliations & Notes
  • Alan McDougal
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Robert Brown
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Maria Ina
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Meredith Weksler
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Heeren Gordhan
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Stuart Williams
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • David A. Ellis
    Aerie Pharmaceuticals Inc, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Alan McDougal Aerie Pharmaceuticals, Code E (Employment); Robert Brown Aerie Pharmaceuticals, Code E (Employment); Maria Ina Aerie Pharmaceuticals, Code E (Employment); Meredith Weksler Aerie Pharmaceuticals, Code E (Employment); Heeren Gordhan Aerie Pharmaceuticals, Code E (Employment); Stuart Williams Aerie Pharmaceuticals, Code E (Employment); David Ellis Aerie Pharmaceuticals, Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 689. doi:
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      Alan McDougal, Robert Brown, Maria Ina, Meredith Weksler, Heeren Gordhan, Stuart Williams, David A. Ellis; Comparison of a Novel Janus Kinase Inhibitor to Available Treatments in a Murine Model of Meibomian Gland Dysfunction. Invest. Ophthalmol. Vis. Sci. 2023;64(8):689.

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

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Abstract

Purpose : The long-term use of an efficacious and safe topical anti-inflammatory compound with a rapid onset of action for dry eye and other chronic ophthalmic inflammation mediated diseases presents an unmet medical need in ophthalmology. In this study, a murine allergic eye disease (AED) model of dry eye disease (DED) was used to evaluate mitigating effects of a novel Janus Kinase inhibitor (JAKi) on DED progression. We tested our novel JAK inhibitor (JAKi) Compound X against a marketed JAKi (Tofacitinib) as well as the approved product Xiidra.

Alan, can you re-word this to include that JAKi have been tested preclinically and clinically in the past, and failed in the clinic we believe due to solubility (and potentially potency) [reference the preclinical and clinical Tofa data]. Then mention how we developed a JAKi to overcome these limitations and compare to both marketed DED products as well as the clinically tested JAKi.

Methods : Using a modified version of a previously established model of AED1, Female C57Bl/6 mice immunized against ovalbumin (OVA) were challenged with a topical OVA solution to induce inflammation and DED progression prior to treatment. Topical solutions of vehicle (Citrate buffer pH=6), 0.3% Compound X, 0.1% Tofacitinib, and 5% lifitegrast (Xiidra) were applied topically TID for 4 days. Subjective masked and randomized clinical scoring of observable ocular inflammation was taken on the day prior to and during the treatment period. Meibomian Glands (MG) were taken post-mortem for qPCR analysis of inflammatory biomarkers.

Results : Topical administration of 0.3% Compound X significantly reduced clinical signs of inflammation including lid edema, conjunctival hyperemia, and MG plugging compared to both 0.1% Tofacitinib and Xiidra. 0.3% Compound X performed similar to the positive control, dexamethasone. Quantitative analysis by qPCR demonstrates that 0.3% X reduced inflammatory biomarkers relative to vehicle in the mouse eyelid.

Conclusions : Compound X demonstrated significant reduction in inflammation and clinical signs of disease in a murine AED model of DED, with improvement relative to current marketed products and a clinically tested JAKi. Compound X represents a novel class of JAK inhibitors that have the potential to be a fast-acting, safe, and efficacious treatment for ocular inflammatory diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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