OTX-DED (episodic dry eye disease)

OFF-LABEL STEROIDS ARE CURRENTLY USED TO TREAT EPISODIC DRY EYE

Our newest product candidate, OTX-DED is a low dose, intracanalicular insert of dexamethasone for the treatment of patients with episodic dry eye disease. OTX-DED is designed to release dexamethasone over a period of two-to-three weeks for the short-term treatment of the signs and symptoms of dry eye disease. While it incorporates the same active drug as DEXTENZA, this is a new product candidate with a lower dose and smaller insert size.

Many dry eye patients experience episodic flares of their signs and symptoms which we believe are likely related to inflammation. Currently available topical steroids are used off label for dry eye and have preservatives which can result in ocular surface toxicity. They may also lead to adverse events such as elevated IOP or cataracts if used chronically. OTX-DED potentially offers these patients the opportunity to be treated with a non-abusable, physician-administered, preservative-free and hands-free steroid therapy. Because OTX-DED has a lower concentration of dexamethasone compared with DEXTENZA, we are able to leverage the DEXTENZA safety package generated to date.

ISSUES WITH EXISTING TREATMENTS

  • Slow onset of action1,2
  • Burning/stinging upon application1,2
  • Topical steroids (which are not FDA-approved for DED) can be misused8-12, 16 
  • Contains preservatives causing ocular toxicity 7-13

KEY PRODUCT ATTRIBUTES

  • Dexamethasone loaded in hydrogel
  • Preservative-free
  • Occludes the canaliculus providing more rapid onset of action
  • Fully biodegradable insert
  • Leverages strong safety profile of DEXTENZA®

Plan to initiate Phase 2 clinical trial in Q1 2021

Caution: NEW DRUG – OTX-DED is currently undergoing clinical evaluation and is limited by law to investigational use only. This product has not been approved by the FDA as safe or effective.

Intracanalicular insertion of OTX-DED

“OTX-DED potentially offers these patients the opportunity to be treated with a non-abusable, physician-administered, preservative-free and hands-free steroid therapy.”

– Michael Goldstein, President, Ophthalmology and CMO – 8/7/2020

About Episodic Dry Eye

Most patients with chronic dry eye disease experience episodic flares3 which can last from a few days to a few weeks.4 Flares may be triggered by various environmental stresses including allergies, dry indoor heating or cooling, smoke, contact lenses, or medications.5 Flares are typically associated with rapid worsening of eye discomfort followed by prolonged, increased inflammation.4 During an acute flare, eye surface inflammation is initiated by a nonspecific innate immune response.4 This may be followed by a slower, more specific adaptive immune response in some patients.4

Many dry eye patients experience exacerbations of their signs and symptoms3 likely related to inflammation.6 Currently available topical ophthalmic steroids are used off label for dry eye and have preservatives7-12 which can result in ocular surface toxicity.13 They may also lead to adverse events such as elevated IOP or increased risk of infection if used chronically.14 OTX-DED potentially offers these patients the opportunity to be treated with a non-abusable, physician-administered, preservative-free and hands-free steroid therapy.15 Because OTX-DED has a lower concentration of dexamethasone compared with DEXTENZA,15 we are able to leverage the DEXTENZA safety package generated to date.

OTX-DED in surgical forceps (image)

OTX-DED in surgical forceps

Comparison of OTX-DED (length 2.25mm) to DEXTENZA (length 3mm) (image)

Comparison of OTX-DED (length 2.25mm) to DEXTENZA (length 3mm)

REFERENCES: 1. ASCRS EyeWorld. https://www.eyeworld.org/download/file/fid/453. Published May 2019. Accessed May 24, 2019 2. Perez VL, Stern ME, Pflugfelder SC. Inflammatory basis for dry eye disease flares. Experimental Eye Research. Published online October 8, 2020:108294. doi:10.1016/j.exer.2020.108294. 3. Lienert, J.P., Tarko, L., Uchino, M., Christen, W.G., Schaumberg, D.A., 2016. Long-term natural history of dry eye disease from the patient’s perspective. Ophthalmology 2016;123(2):425–433. 4. Perez VL, Stern ME, Pflugfelder SC. Inflammatory basis for dry eye disease flares. Exp Eye Res. 2020;201:108294.  5. Calonge M, Labetoulle M, Messmer EM, et al. Controlled adverse environment chambers in dry eye research. Curr Eye Res. 2018;43(4):445–450. 6. Barabino S, Chen Y, Chauhan S, et al. Ocular surface immunity: Homeostatic mechanisms and their disruption in dry eye disease. Prog Retin Eye Res. 2012;31(3):271–285. 7. Cutolo CA, Barabino S, Bonzano C, Traverso CE. The Use of Topical Corticosteroids for Treatment of Dry Eye Syndrome. Ocul Immunol Inflamm. 2019;27(2):266-275. 8. LOTEMAX (loteprednol etabonate ophthalmic gel) 0.5% [prescribing information]. Tampa, FL: Bausch & Lomb, Inc.; 2012 9. LOTEMAX SM (loteprednol etabonate ophthalmic gel) 0.38% [prescribing information]. Bridgewater, NJ: Bausch & Lomb, Inc.; 2019. 10. FML (fluorometholone ophthalmic suspension, USP) 0.1% [prescribing information]. Irvine, CA: Allergan, Inc.; 2013 11. PRED FORTE (prednisolone acetate ophthalmic suspension, USP) 1% [prescribing information]. Irvine, CA: Allergan, Inc.; 2017 12. PRED MILD (prednisolone acetate ophthalmic suspension, USP) 0.12% [prescribing information]. Madison, NJ: Allergan USA, Inc.; 2018 13. Epstein SP, Ahdoot M, Marcus E, Asbell PA. Comparative toxicity of preservatives on immortalized corneal and conjunctival epithelial cells. J Ocul Pharmacol Ther. 2009;25(2):113-119. doi:10.1089/jop.2008.0098 14. Pleyer U, Ursell PG, Rama P. Intraocular pressure effects of common topical steroids for post-cataract inflammation: Are they all the same? Ophthalmol Ther. 2013;2(2):55–72. 15. Data on File 01026. Ocular Therapeutix, Inc. 16.Farkouh A, Frigo P, Czejka M. Systemic side effects of eye drops: a pharmacokinetic perspective. Clin Ophthalmol. 2016;10:2433-2441.