Azura Ophthalmics announces positive results from Phase 2 clinical trial of AZR-MD-001 in patients with contact lens discomfort

(Image Credit AobeStock/revers_jr)

Azura Ophthalmics Ltd announced positive topline efficacy and safety results from a Phase 2 study (NCT05548491) of AZR-MD-001 in patients with contact lens discomfort (CLD) who could not comfortably wear their lenses as desired and who demonstrated signs of meibomian gland dysfunction (MGD).

According to the company, the trial met its primary endpoint of showing a statistically significant improvement in meibomian glands yielding liquid secretion (MGYLS; number of open glands).

Moreover, the company reported in its news release the study also met additional secondary and clinically meaningful endpoints, including significant improvements in meibum quality (measured by Meibomian Gland Score, MGS); tear stability (measured by tear break up time, TBUT); ocular surface staining (measured by both fluorescein and lissamine green staining); and contact lens wear time.

The company also noted AZR-MD-001 was safe and well tolerated. All observed adverse events were mild to moderate in severity and none resulted in an end to the treatment. This company also noted this is the second positive Phase 2 study of AZR-MD-001 to demonstrate statistically significant improvements across multiple sign and symptom endpoints in patients with MGD.

In a conversation with Ophthalmology Times, Azura CEO Marc Gleeson pointed out that MGD is the root cause of many downstream ocular surface conditions that impact quality of life and vision for patients, including contact lens discomfort. He noted the study also reinforces the mechanism of action of AZR-MD-001 as a drug that targets the underlying cause of MGD.

“By opening up blocked glands and improving the quality of the tear film, it appears that many of these ocular surface conditions can be resolved,” Gleeson said.

In addition to meeting its primary MGYLS endpoint, Gleeson pointed out the company is 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.

“A key secondary endpoint was that we have been able to demonstrate that patients were able to increase their comfortable wear time, by a little over 3 hours,” he said. “And that's significant and clinically meaningful. And so what that means is that patients who have the potential to improve their comfortable way time so that they can wear their contact lenses throughout the whole day. “

The results have been encouraging, Gleeson added.

“It also validates the underlying mechanism of action of 001 as a key target for opening the glands,” he explained.

Gleeson added the study is offering hope for patients as it moves on to the next step on the clinical trial ladder.

“We now have 2 studies showing AZR-MD-001 can improve the signs and symptoms of MGD and we look forward to discussing these results with the FDA as we advance our Phase 3 development program,” he said.

According to the company, MGD is a chronic condition that causes the glands in the eyelids to become blocked, impacting the quality and quantity of meibum secretions in the upper and lower eyelids. This leads to several downstream ocular surface symptoms including dryness, pain, irritation, reduced quality of vision, and CLD. Many patients who have signs of ocular surface disease including MGD and who would like to wear contact lenses find they cannot wear them for as long as desired and may stop using contact lenses if wearing them becomes too bothersome or uncomfortable.

Lyndon Jones, PhD, director and professor at the Centre for Ocular Research & Education in Ontario, Canada, explained in the news release that MGD is one of the causes of CLD, and many patients give up on wearing contact lenses altogether due to the irritation they experience.

“Innovation in contact lens design and materials intended to offer a more comfortable patient experience has stalled, with reports of discomfort at the end of the day being similar for the past 20 years,” Jones said in the news release.

Moreover, Jones noted this leaves patients frustrated and seeking alternative vision correction options.

“With these AZR-MD-001 data, I’m encouraged to see a potential treatment that may address the underlying cause of contact lens discomfort, and I believe my patients would find an extra three hours of comfortable contact lens wear time to be very meaningful,” Jones explained.

According to the company, its Phase 2 trial was a multi-center, vehicle-controlled study that evaluated the safety and efficacy of AZR-MD-001 0.5% compared to its vehicle in 67 patients diagnosed with Contact Lens Discomfort who could not comfortably wear their contact lenses as desired and who had signs of MGD. Patients self-administered AZR-MD-001 or its vehicle to the lower eyelid at bedtime twice weekly for 3 months.

The company noted the prospectively defined primary efficacy endpoint was the number of open glands as measured by the MGYLS score. Moreover, the secondary endpoints included comfortable contact lens wear time reported in minutes, corneal and conjunctival staining using the Oxford scale, and responder analyses based upon published thresholds for MGYLS and MGS. The trial was supported by a grant from CUREator, a biotechnology incubator run by Brandon BioCatalyst to support and accelerate the development of Australian biomedical research and innovations.

According to the company, AZR-MD-001 0.5% achieved statistically significant differences compared to vehicle in both signs and symptoms at month 3:

• Primary endpoint:
  • Significant improvements in MGYLS score, 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:
  • Significantly more patients treated with AZR-MD-001 had at least 5 more glands opened, as measured by MGYLS responder rate, compared to vehicle (58.2% vs 6.1%, p< 0001).
  • Significantly more patients treated with AZR-MD-001 had their meibum quality return to normal levels, as measured by MGS responder rate, compared to vehicle (97.1% vs. 33.6%, p<0.0001).
  • Comfortable contact lens wear time increased by 192 minutes for AZR-MD-001 treated patients compared to 0.65 minutes for vehicle treated patients (p<0.0001).
  • AZR-MD-001 significantly decreased fluorescein and lissamine green ocular surface staining:
    • AZR-MD-001 was associated with a significant shift toward lower fluorescein staining scores with 67.1% of patients achieving a score of 0 compared to 15.2% of patients treated with vehicle (p=0.0001).
    • AZR-MD-001 was associated with a significant shift toward lower nasal lissamine green staining scores with 32.4% of patients achieving a score of 0 compared to 18.1% of patients treated with vehicle (p=0.0038).
    • AZR-MD-001 was associated with a significant shift toward lower temporal lissamine green staining scores with 35.5% of patients achieving a score of 0 compared to 12.1% of patients treated with vehicle (p=0.0205).

All treatment-emergent adverse events (TEAEs) were mild to moderate with no serious treatment-related AEs. No patients discontinued the study due to adverse events, according to the news release.

“Ultimately, If approved, we hope this data will allow patients who have stopped wearing their contact lenses due to contact lens discomfort, to be able to get a longer, more comfortable wear time,” Gleeson said.

About AZR-MD-001

Azura’s lead clinical-stage, investigational drug candidate AZR-MD-001 harnesses the power of selenium sulfide (SeS2) in an easy-to-use ophthalmic ointment preparation applied directly to the meibomian glands in the lower eyelid. AZR-MD-001 is thought to have a multi-modal mechanism of action that treats the pathophysiology of MGD along with the resulting ocular surface symptoms. It breaks down the bonds between abnormal keratin proteins to soften the blockage, slows down the production of keratin to prevent future blockages, and increases the quality and quantity of meibum produced by the meibomian glands.

AZR-MD-001 is currently being studied to evaluate the safety, efficacy, and tolerability of the study drug in patients with clinical signs of MGD.

Contact lens discomfort

CLD is a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, that can lead to decreased wear time and discontinuation of contact lens use. CLD patients experience symptoms of ocular discomfort (e.g., dryness, irritation, discomfort, fatigue) that increase in severity over the day while the patient is wearing the contact lenses.¹

Meibomian gland dysfunction

Meibomian Gland Dysfunction (MGD) is a chronic and progressive condition associated with blockage of the meibomian glands and alteration in the quality of expressed meibum which can end in gland atrophy. It is a leading cause of dry eye disease and contributor to CLD.^2,3,4

References:

1. Nichols JJ, Willcox MDP, Bron AJ, et al. The TFOS International Workshop on Contact Lens Discomfort: Executive Summary. Invest Ophthalmol Vis Sci. 2013;54:TFOS7–TFOS13

2. Milner, M. S., Beckman, K. A., Luchs, J. I., Allen, Q. B., Awdeh, R. M., Berdahl, J., Boland, T. S., Buznego, C., Gira, J. P., Goldberg, D. F., Goldman, D., Goyal, R. K., Jackson, M. A., Katz, J., Kim, T., Majmudar, P. A., Malhotra, R. P., McDonald, M. B., Rajpal, R. K., Raviv, T., … Yeu, E. (2017). Dysfunctional tear syndrome: dry eye disease and associated tear film disorders – new strategies for diagnosis and treatment. Current opinion in ophthalmology, 27 Suppl 1(Suppl 1), 3–47. https://doi.org/10.1097/01.icu.0000512373.81749.b7.

3. Foulks GN, Bran AJ. Meibomian gland dysfunction: a clinical scheme for description, diagnosis, classification, and grading. Ocul Surf. 2003;1:107-126.

4. Efron N, Jones L, Bron AJ, et al. The TFOS International Workshop on Contact Lens Discomfort: Report of the Contact Lens Interactions With the Ocular Surface and Adnexa Subcommittee. Invest Ophthalmol Vis Sci. 2013;54:TFOS98–TFOS122.