Azura Ophthalmics Ltd. announced positive topline efficacy and safety data from a phase 2 study evaluating AZR-MD-001 for contact lens discomfort (CLD) patients demonstrating signs of meibomian gland dysfunction (MGD).
Updated January 5, 2024: Glance President Jaclyn Garlich, OD, FAAO, spoke with Azura CEO Marc Gleeson on the company's new phase 2 data.
Let’s start with 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 potentially:
- 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.
Gleeson shares more below.
Now this study.
The two-stage, multi-center, vehicle-controlled phase 2 study (NCT05548491) enrolled 67 patients (aged 18+) with CLD.
Patients were required to have a history of contact lens wear for at least 6 months as well as meibomian gland obstruction (based on meibomian gland secretion [MGS] score of ≤12 for 15 glands of the lower lid) in both eyes.
The purpose: to determine common symptoms (stage 1) and to examine the safety, tolerability, and pharmacodynamics of AZR-MD-001 (stage 2).
Break these stages down.
- Stage 1
- Up to 12 participants experiencing symptoms of CLD and concomitant MGD symptoms.
- Following screening (either immediately after or up to 14 days later) participants underwent a hybrid interview of symptom and cognitive debriefing.
- Stage 2
- Multi-center, single-masked, vehicle-controlled, randomized, parallel group study
- For a 3-month period, CLD participants were randomly assigned (1:1) to self-administer either of the following at nightime, twice weekly, for 3 months.
- AZR-MD-001 ointment / semi-solid drug (1.0%)
- AZR-MD-001 vehicle
And the outcome measures?
Three primary outcome measures, all evaluated at 3 months, included:
- Meibomian Glands Yielding Liquid Secretion (MGYLS)
- Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8)
- Fluctuating vision score range: 0 (normal) to 9 (impacted vision)
- CLDEQ-8 total score
- Score range: 0 (normal) to 37 (impacted contact use)
Secondary measures were:
- Meibum quality (via MGS score)
- Tear stability (via tear break-up time [TBUT])
- Ocular surface staining (via fluorescein and lissamine green staining)
- Contact lens wear time
Now the findings.
Per Azura, the study met its primary endpoint—exhibiting a “statistically significant improvement in (MGYLS) …with patients experiencing significantly more open glands on AZR-MD-001 than vehicle (5.0 glands vs 1.6 glands, p< 0.0001).”Secondary endpoints were also met, with “significant improvements” in all measures:
- AZR-MD-001-treated patients had at least 5 more glands opened, compared to vehicle (58.2% vs 6.1%, p< 0001).
- Significantly more of these participants also had their meibum quality return to normal levels vs vehicle (97.1% vs. 33.6%, p< 0.0001).
- Both fluorescein and lissamine green ocular surface staining also decreased significantly when administered AZR-MD-001 vs vehicle, respectively:
- 67% at a score of 0 vs 15.2% (fluorescein)
- 32.4% at a score of 0 vs 18.1% (lissamine- nasal)
- 35.5% at a score of 0 vs 12.1% (lissamine- temporal)
What about contact lens wear time?
Comfortable lens wear time increased by 192 minutes for patients treated with AZR-MD-001 vs just 0.65 minutes for vehicle-treated participants.
Any adverse events?
The company reported all treatment-emergent adverse events (TEAEs) noted were mild to moderate in severity and did not lead to any patients discontinuing treatment.
Significance?
Per Gleeson: “We are especially encouraged that AZD-MD-001 allowed patients who had given up using contacts to wear their contacts again—safely and comfortably—for an additional three hours every day over their normal wear time.”
Also of interest, according to Azura: this phase 2 study is the second on AZR-MD-001 in which it demonstrated “statistically significant improvements across multiple sign and symptom endpoints in patients with MGD.”
The second phase 2 study, you say?
Yup. Back in August 2023, the company reported positive 3-month data from a separate phase 2 study (NCT03652051) on AZR-MD-001 in patients with MGD and evaporative dry eye disease (DED).
Read that coverage here.
And more recently, in October 2023, Azura released updated 6-month results at the American Academy of Optometry (AAOPT) meeting. See here for more details.
Gotcha. So what’s next?
With supporting positive data from two phase 2 studies, the company intends to discuss the results with the FDA and “advance our phase development program,” stated Gleeson.