Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial

The Ocular Surface

Volume 29, July 2023, Pages 537-546

Stephanie L. Watson, Lyndon W. Jones, Fiona Stapleton, Mark Hinds, Alison Ng, Jacqueline Tan, Yair Alster, Charles Bosworth, Omer Rafaeli, Venita DePuy, The CELESTIAL STUDY Group

Over the past few years our own, Mark Hinds, with his team at Ophthalmic Trials Australia (www.ot-au.com) have been involved in the multi-centered investigation into the efficacy and safety of selenium sulfide ointment in the setting of meibomian gland dysfunction (MGD) and dry eye disease. This ground breaking research has shown promise for those patients with evaporative dry eye disease.

MGD is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion. Terminal duct obstruction is caused by hyperkeratinization of the ductal epithelium. This may result in alteration of the tear film, symptoms of eye irritation, and ocular surface disease such as evaporative dry eye. The principal clinical consequence of obstructive MGD is evaporative dry eye syndrome and large population based studies estimate that over 60% of patients with dry eye symptoms also have
MGD.

MGD may be diagnosed by meibomian gland expression alone, with demonstration of an altered quality of expressed secretions, and/or by a loss of gland functionality. Population based studies have estimated the prevalence of MGD to vary between 3.5% and 70% of the general population with total prevalence estimated at over 100 million Americans. The prevalence of MGD appears higher in Asian populations (i.e., 46.5% to 69.3%) and increases with age. Risk factors in the pathogenesis of obstructive MGD include age, hormonal disturbances, and environmental influences (e.g., contact lenses).

The recognition that terminal duct obstruction from hyperkeratinization of the ductal epithelium on meibomian glands is a core mechanism behind meibomian gland dysfunction (MGD) is consistent with clinical experience demonstrating that effective treatments for MGD require resolution of ductal obstruction and evacuation of glandular contents. To date, there are no approved pharmacological treatments for terminal duct obstruction from hyperkeratinization associated with MGD. The primary treatment goal in MGD is ensuring a healthy lipid layer for the ocular surface by improving tear film stability, which is dependent on high-quality meibum secretion and normal flow.

The investigational product (AZR-MD-001) is a keratolytic, keratostatic and lipogenic giving a significant multifaceted therapeutic effect in short time (findings suggest 2/52 with bi-weekly application).

From an antimicrobial perspective, seeing that selenium sulfide shampoos and lotions have also been shown to have antimicrobial activity against several different genera of fungi (e.g., Pityrosporum) and bacteria (e.g., Staphylococcus, Leptospira and Micrococcus), which may have a down stream therapeutic effect in the treatment of MGD.

Further research continues and subsequent publications will follow. Look out for Posters / Abstracts at ARVO 2023, ASCRS 2023, AAO 2023, and AAOPT 2023.

The following is the Abstract excerpt:

Abstract

Purpose

Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD.

Methods

A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs).

Results

AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug).

Conclusions

Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated.

Trial registration

ClinicalTrials.gov Identifier: NCT03652051, ANZCTR Registration Number: AZ201801.

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