Eyelid Rx With AZR-MD-001

Within the current pharmaceutical treatment paradigm of evaporative dry eye disease (DED), most agents focus on relieving downstream signs and symptoms—inflammation, dryness, and itching. At Azura Ophthalmics, we’re focused on treating the root cause of evaporative DED at the glandular level, having recognized that meibomian gland dysfunction (MGD) is a disease of the skin—specifically, the eyelids.

Meibomian and sebaceous glands share a common embryological origin, and many pathological features of sebaceous gland disorders, such as comedonal acne, are mirrored in MGD.¹ This insight led us to evaluate dermatologic agents with potential relevance to glandular dysfunction in the ocular adnexa. We believe that restoring gland function will lead to improved tear stability, ocular comfort, and visual performance.

AZR-MD-001: A Multimodal Therapeutic

Our lead candidate, AZR-MD-001, is a topical ointment formulated with selenium sulfide, a compound well established in dermatology for treating seborrheic dermatitis. Selenium sulfide’s keratolytic properties—disrupting disulfide bonds, modulating keratinocyte turnover, and reducing abnormal keratin production—are particularly relevant in addressing the keratinized obstruction often present in meibomian glands.²

Beyond its keratolytic effect, selenium sulfide has been observed to stimulate lipid production in sebaceous glands,³ which is advantageous in restoring lipid secretion in MGD. We hypothesize that selenium sulfide promotes the maturation of acinar cells in the meibomian glands, enhancing both the quantity and quality of meibum.

Efficacy and Tolerability Data

In the CELESTIAL phase 2 study, AZR-MD-001 demonstrated statistically significant improvements in both anatomical and patient-reported outcomes.⁴ The trial included patients with evaporative dry eye associated with MGD and evaluated the dosing of 0.5% and 1.0% selenium sulfide formulations compared to vehicle. Key 3-month findings included: a statistically significant average increase in meibomian glands yielding liquid secretion (MGYLS) from baseline of 4.2; a statistically significant mean improvement in OSDI scores of 7.3; and continued improvement in symptom and glandular function measures through 6 months, without evidence of a plateau effect.

Patients applied a small, controlled amount of ointment to the eyelids twice per week at bedtime to avoid exposure to the ocular surface and to minimize stinging and irritation. Initial reports of mild eyelid discomfort diminished with continued use.

Currently underway is our phase 3 ASTRO study, with 562 patients enrolled across 14 clinical sites in the U.S. and primary endpoints focused on MGYLS and OSDI. Importantly, the study includes a 12-month masked treatment period to meet regulatory requirements for the long-term safety of AZR-MD-001 in chronic use.

We anticipate top-line data from ASTRO in Q4 of this year, which will inform our new drug application (NDA) to the FDA.

Future Pipeline Development

Beyond AZR-MD-001, Azura is developing novel compounds by chemically conjugating keratolytic agents with established ophthalmic therapies, such as azithromycin and lifitegrast. These modified molecules in preclinical development are designed to be metabolized within the eyelid for delivery to the ocular surface via glandular secretion.

Also, preliminary formulation studies suggest selenium sulfide may affect Demodex mite behavior and reduce erythema and scaling to improve overall eyelid health.

The Azura portfolio reflects our commitment to developing new tools that not only treat symptoms but address the source of dysfunction at its origin: the eyelid.

1. Knop E, et al. Invest Ophthalmol Vis Sci. 2011;52(4):1938–1978.

2. Gupta P, et al. Cataract & Refractive Surgery Today (suppl). 2021. https://crstoday.com/articles/nov-dec-2021/meibomian-gland-dysfunction-a-dermatologic-perspective.

3. Shuster S, et al. Physiol Rev. 1974;54(2):181–217.

4. Watson SL, et al. Ocul Surf. 2023:29:537-546.

For more information: https://azuraophthalmics.com/

For inquiries, contact Marc Gleeson at Marc.Gleeson@azuraophthalmics.com