June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Suprachoroidal Delivery of Suspensions of Tyrosine Kinase Inhibitor, Complement Inhibitor, and Corticosteroid: Preclinical and Clinical Correlates
Author Affiliations & Notes
  • Debra A Goldstein
    Ophthalmology, Northwestern Med Faculty Foundation, Chicago, Illinois, United States
  • Thomas A Ciulla
    Indiana University School of Medicine, Indiana, United States
    Clearside Biomedical, Inc., Georgia, United States
  • Footnotes
    Commercial Relationships   Debra Goldstein, Abbvie (C), allergan (C), Clearside (C); Thomas Ciulla, Clearside Biomedical, Inc. (E), Clearside Biomedical, Inc. (I)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2898. doi:
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    • Get Citation

      Debra A Goldstein, Thomas A Ciulla; Suprachoroidal Delivery of Suspensions of Tyrosine Kinase Inhibitor, Complement Inhibitor, and Corticosteroid: Preclinical and Clinical Correlates. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2898.

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

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Abstract

Purpose : Tyrosine kinase inhibitors (TKI), complement inhibitors, and corticosteroids have multiple potential therapeutic implications in retinal and uveitic disorders. The purpose of this research is to analyze preclinical and clinical studies of these suprachoroidal suspensions to characterize key attributes of the suprachoroidal delivery platform.

Methods : Suprachoroidal (SC) delivery of TKI, complement inhibitor, and steroid suspensions in rabbits were conducted to characterize compartmentalization, durability, efficacy, and reproducibility of SC delivery. Preclinical results of the steroid suspension were compared to clinical trial results to assess for clinical correlations. Physician user information from the Phase 3 AZALEA safety study was assessed to characterize reliability of this in-office technique.

Results : In preclinical rabbit studies, SC delivery of TKI, complement inhibitor, and steroid suspensions yielded greater concentrations in the sclera/choroid/retina than anterior tissues, and durability of posterior levels ≥ 3 months. Preclinical neovascularization and uveitis models demonstrated signs of efficacy with TKI and TA respectively; SC injection of TA was as effective as intravitreal injection of TA at 1/10 dosage. For TA, Phase 3 uveitis trials show correlating results to preclinical studies, with clinically meaningful efficacy (47% subjects gaining >15 EDTRS BVCA letters after 2 quarterly SC injections of 4 mg CLS-TA), durability (50% requiring no additional treatment for 6 months after 2 quarterly SC injections of 4 mg CLS-TA) and low IOP and cataract adverse events. Over 80% of physicians in AZALEA experienced no new challenges with SC injections compared to other types of ocular injections and observed no serious adverse events related to the procedure.

Conclusions : SC delivery of suspensions of TKI, complement inhibitor, and steroid demonstrate prolonged therapeutic levels with the potential for sustained release and high bioavailability, and show compartmentalization with the potential to minimize adverse effects. These attributes correlate to clinical trial outcomes for steroids; further study of TKI and complement factors suspensions are warranted.

This is a 2020 ARVO Annual Meeting abstract.

 

SC delivery of TKI (axitinib), corticosteroid (triamcinolone acetonide), and compliment inhibitor suspensions in rabbits show high bioavailability in RPE/choroid/sclera for ≥ 90 days

SC delivery of TKI (axitinib), corticosteroid (triamcinolone acetonide), and compliment inhibitor suspensions in rabbits show high bioavailability in RPE/choroid/sclera for ≥ 90 days

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