Azura Ophthalmics Limited reported new data published in The Ocular Surface for its phase 2 trial on AZR-MD-001 for the potential treatment of meibomian gland dysfunction (MGD)
Refresh me on AZR-MD-001.
AZR-MD-001 is a selenium sulfide ophthalmic ointment designed to be applied directly to the surface of the lower eyelid as a potential treatment for MGD.
How does it work?
Per Azura, the formulation is intended to target the primary pathophysiology of abnormal keratin production and obstruction, poor meibum quality, and resulting ocular signs and symptoms by:
- Slowing down the rate of keratinocyte proliferation and keratin production (slowing meibomian gland plug formation and obstruction.
- Softening keratin aggregates by breaking down disulfide bonds, opening obstructions, and improving meibum quality and flow through the meibomian glands.
- Stimulating lipogenesis to increase lipid quantity produced by the meibum glands.
- Killing mites and bacteria on eyelash follicles.
Gotcha. And this phase 2 study?
The randomized, double-masked, vehicle-controlled, parallel-group, multicenter trial (NCT03652051) enrolled 245 patients (ages 18+) diagnosed with MGD and evaporative dry eye disease (DED).
Conducted at 29 sites across Australia, New Zealand, and Canada, patients were enrolled based on the following criteria at screening and baseline:
- Best-corrected visual acuity (BCVA) of 20/40 or better
- Evidence of meibomian gland obstruction
- Reported dry eye signs and symptoms (with past 3 months)
See here for exclusion criteria.
How about the dosages?
Patients were randomized 1:1 to receive one of two doses of AZR-MD-001 (0.5% or 1.0%) or vehicle in both eyes, applied twice weekly immediately before sleep on the lower eyelids.
To note, all participants were stratified by MGD diagnosis duration (<5 or ≥5 years) and Meibomian Gland Secretion (MGS) score (<6, or ≥6 and ≤ 12) at baseline.
What was measured?
The primary outcome measures included, at Month 3:
- MGS Score
- Change from baseline in MGS (0 to 45) at Month 3
- Meibomian glands yielding liquid secretion (MGYLS)
- Change from baseline in MGYLS (0 to 15) at Month 3
Secondary outcome measures were MGS and MGYLS measured at:
- Day 14
- Month 1
- Month 1.5
Anything else?
According to the authors, patients were evaluated with slit-lamp biomicroscopy to assess:
- Sodium fluorescein corneal staining (Oxford Scale)
- Lissamine green conjunctival staining (Oxford Scale)
- Eyelid margin erythema/telangiectasia
- Overall meibomian gland analysis.
Did all patients complete the study?
Actually, no. Of the 245 patients who enrolled, 14.3% (33) discontinued before the Month 3 visit. The completion rate for each of the doses was:
- AZR-MD-001 0.5%
- 79.3% (n = 65/82)
- AZR-MD-001 1.0%
- 80.7% (n = 67/83)
- Vehicle
- 95% (n = 76/80)
Over the study period, 94.2% (196) of patients administered the target number of doses (24).
And the findings?
AZR-MD-001 0.5% met both primary endpoints, with a significantly greater improvement noted in MGYLS scores from baseline to Month 3 vs vehicle.
Similarly, the 0.5% dosage resulted in a significantly greater improvement from baseline to Month 3 for the Ocular Surface Disease Index (OSDI) total score when compared to vehicle.
Meaning …
Treatment with AZR-MD-001 0.5% resulted in more open meibomian glands and greater symptom relief than vehicle.
What about the 1.0% dosage?
Per study authors, while “there was numerical improvement with AZR-MD-001 1.0%,” both co-primary endpoints did not achieve statistical significance.
And the secondary outcomes?
For all timepoints (Day 14, Month 1.5, and Month 3), researchers noted a numerically higher value of responders treated with AZR-MD-001 than vehicle—although none reached statistical significance.
Any adverse events?
Across all three groups, 44.9% (245) of patients reported a treatment-emergent adverse event (TEAE); of those, slightly more than 19% (47) were non-ophthalmic and 48.2% (118) were ophthalmic.
These included:
- Application-site pain
- Increase lacrimation
- Superficial punctate keratitis
- Corneal staining
- Eye pain
- Eye irritation
- Application-site irritation
- Eye inflammation
To note, 93.6% of the ophthalmic AEs for AZR-MD-001 were mild to moderate.
Additionally, five serious TEAEs were reported among four patients:
- Pericarditis
- Thyroid mass
- Pneumonia
- Post-procedural hemorrhage
- Nephrolithiasis
Overall?
Based on the data, between the two concentrations of AZR-MD-001, 0.5% performed more consistently (and significantly) than 1.0%.
How does this compare to prior research on the drug?
While both concentrations led to benefits for lipid production, these latest findings are consistent with a previous phase 2 study (NCT04391959) in 2021, which also determined AZR-MD-001 0.5% to be more likely than 1.0% to improve MGD signs and symptoms.
Significance?
If approved by the FDA, AZR-MD-001 could potentially become a first-in-class ophthalmic keratolytic to treat lid margin disease, starting first with MGD.