March 4, 2021
Azura Ophthalmics moves into registration studies following positive Phase 2 Program results which could see its treatment for Meibomian gland disfunction – the leading cause of Dry Eye Disease – complete its first registration study by early next year
Azura Ophthalmics Ltd., a clinical-stage company developing innovative therapies for Meibomian gland dysfunction (MGD), today announces positive results from its milestone Phase 2 Program, as the company progresses a new potential treatment for a chronic condition affecting millions globally.
The Phase 2 Program found that AZR-MD-001 showed improvements with two doses (0.5% and 1.0%). Statistically significant improvement in signs and symptoms of MGD were demonstrated relative to the control arm.
As measured against the Ocular Surface Disease Index (OSDI)©, a patient symptom score used by clinicians, 58% and 42% of patients in the 0.5% and 1.0% dose groups respectively became non-symptomatic after three months of treatment, compared to 16% of patients in the control arm.
“We are thrilled by the positive results showing a statistically significant and clinically meaningful improvement in the signs and symptoms of Meibomian gland dysfunction, which validates our multi-mechanism of action and suggests that AZR-MD-001 has the potential to be a first-in-class treatment option for patients with Meibomian gland dysfunction,” said Marc Gleeson, CEO of Azura. “The study findings also provide insight into the target populations, appropriate dosing and endpoints for our registration study.”
Azura has commenced a registration study across 12 clinical research centres in Australia and New Zealand which will most likely be completed by early 2022. Registration studies are the final stage before potential Food and Drug (FDA) regulatory approval.
MGD, the leading cause of Dry Eye Disease, is a chronic and progressive condition where the glands that line the eyelids become blocked, preventing them from secreting enough oil into the tear film needed to properly lubricate the eye. MGD represents one of the largest and most underserved segments in ophthalmology – affecting more than 30 million adults in the US alone – but current treatment options are limited and do not address the root cause of the disease.
Azura raised AU$28m last October to finance the registration study and FDA registration process. The round included participation from existing investors, including, Brandon Capital’s Medical Research Commercialisation Fund (MRCF), OrbiMed, TPG Biotech, and Ganot Capital.
Research shows that MGD is the main cause of Dry Eye Disease. Current treatment options for Dry Eye Disease are primarily focused on treating inflammation and providing temporary relief with artificial tears, which only account for a minority of the Dry Eye Disease population. AZR-MD-001 is designed to restore Meibomian gland function by addressing the abnormal hyperkeratinization that blocks the glands, alters the quality of the oil and prevents the secretion of lipids into the tears. There are currently no approved medicines for the treatment of MGD.
“Though there are approved treatments for Dry Eye Disease, they are only appropriate for the patients where inflammation is the cause of the disease,” said Edward Holland, M.D., Director, Cornea Services/Professor of Clinical Ophthalmology, Cincinnati Eye Institute/University of Cincinnati. “Research shows that 86% of people with Dry Eye Disease exhibit signs of Meibomian gland dysfunction1. By addressing the underlying cause of Meibomian gland dysfunction that leads to Dry Eye, Azura is taking an entirely different approach to the disease that has the potential to benefit a much broader population of patients.”
Australia’s effective handling of the Covid-19 pandemic has meant that Azura’s clinical trial program has been able to continue relatively undisrupted, which would not have been possible if trials were being conducted in the US or Europe, Mr Gleeson continues. “Meibomian gland dysfunction is a debilitating disease which has a terrible impact on millions of peoples’ lives around the world. Our goal is to get our treatment registered for use, as quickly as possible, and Australia’s management of the pandemic has meant little disruption to our clinical trial program.
“Clinical trial recruitment and participation are at normal levels across Australia and New Zealand, something few countries can boast. Trials in Australia have high enrollment rates, in part because contract research organisations offer incentives for citizens to participate and the Australian government promotes clinical trials among consumers and health care providers, making it easy to get involved.”
About the Phase 2 Program
The program was a multi-center, double-masked, vehicle-controlled integrated analyses of four phase 2 studies that evaluated the safety and efficacy of AZR-MD-001 (0.1%, 0.5% and 1.0%) in 95 patients with MGD. Patients were dosed twice weekly at night time. Primary endpoints included patient-reported symptoms as measured by the Ocular Surface Disease Index© (OSDI) score, the quality of fluid secretion as measured by the Meibomian Gland Score (MGS) and the number of glands secreting meibum as measured by the Meibomian Glands Yielding Liquid Secretion (MGYLS) score.
There was a statistically significant and clinically meaningful reduction of symptoms as measured by a reduction in OSDI score in the two highest doses tested (0.5% and 1.0%) compared to baseline and control:
- Statistically significant improvements from baseline were observed in both the 0.5% and 1.0% dose groups (p<0.01) with significant improvements over control observed by Month 3 in the 0.5% group (p<0.05)
- Up to 58% of patients became non-symptomatic (score of <13) after 3 months of treatment compared to 16% of patients in the control arm (p<0.05)
Similar trends were observed in the secondary endpoint of patient-reported symptoms as measured by the Standardized Patient Evaluation of Eye Dryness (SPEED) Questionnaire. Results demonstrated a statistically significant difference from baseline and control in the 1.0% dose group (p<0.05) and a statistically significant change from baseline in the 0.5% dose group (p<0.05) and compared to control (p<0.08).
Results also indicated a clear dose-response in the number of glands secreting meibum as measured by a statistically significant improvement in MGYLS score in the two highest doses tested (0.5%, 1.0%) compared to baseline and control:
- Statistically significant increases from baseline were observed in both the 0.5% and 1.0% dose groups (p<0.01) with significant improvements over control observed as early as Month 1 with 1.0% (p<0.01) and continuing to Month 3 (p<0.01)
- Up to 46% of patients achieved a clinically meaningful increase in MGYLS compared to 8% of patients in the control arm (p<0.01)
Additionally, results further indicated a clear dose-response in the quality of meibum secreted as measured by a statistically significant improvement in MGS in both dose groups (0.5%, 1.0%) compared to baseline and in the highest dose tested (1.0%) compared to control:
- Statistically significant increases from baseline were observed in both the 0.5% and 1.0% dose groups (p<0.01) with significant improvements over control observed as early as Month 2 with 1.0% (p<0.05) and continuing to Month 3 (p<0.01)
- Up to 59% of patients returned to a normal range (score of >12) after 3 months of treatment compared to 31% of patients on control (p<0.05)
AZR-MD-001 was well tolerated with no serious ocular treatment emergent adverse events (TEAEs). The most common TEAEs were application site irritation, stinging upon application, and watery eyes, which only occurred in patients in the 1.0% dose group.
About Meibomian Gland Dysfunction
Meibomian gland dysfunction – a chronic and progressive condition associated with blockage of the Meibomian glands preventing them from secreting enough oil into the tear film – is the leading cause of Dry Eye Disease (DED). Estimates suggest that 86% of patients who suffer from DED exhibit signs of MGD.1 MGD is commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretion.2 There are no approved prescription pharmaceutical agents that specifically treat these glandular changes. If left untreated, MGD will alter the tear film, resulting in damage to the front of the eye and severe discomfort from associated ocular surface diseases.
Azura’s lead product candidate, AZR-MD-001, is a topical ointment that has been developed to yield properties ideal for ophthalmic use. The formulation is applied to the lower lid margin twice a week before bedtime.
AZR-MD-001 leverages SeS2 as the active ingredient. SeS2 has been identified to be an ideal candidate for treating MGD due to its multi-mechanism of action targeting the pathophysiology of MGD. 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 quantity of lipid produced by the Meibomian glands. If approved, AZR-MD-001 will be a first-in-class ophthalmic keratolytic for the treatment of lid margin diseases, starting with MGD.
About Azura Ophthalmics, Ltd.
Azura Ophthalmics is a clinical-stage company headquartered in Tel Aviv-Yafo, Israel with operations in Australia and the U.S. The company is developing an innovative portfolio of compounds to advance treatments for MGD, the leading cause of DED. By targeting the root cause of MGD, Azura brings the promise of improved health and well-being to millions of people worldwide who suffer from MGD and other ocular surface diseases where treatment options are currently lacking.
Azura Ophthalmics has a robust clinical development pipeline with an initial focus on developing medicines to treat Meibomian gland dysfunction (MGD) and Contact Lens Discomfort (CLD). The company’s pipeline also includes new chemical entities in pre-clinical stages for a number of ocular and lid margin diseases, including MGD mixed disease, inflammatory/aqueous deficient Dry Eye, blepharitis, and ocular manifestations of graft-versus-host disease (GvHD).
Azura is underpinned by an experienced management team with an established track record of successfully developing and commercializing novel treatments for ocular surface diseases. For more information visit: www.azuraophthalmics.com and follow Azura on LinkedIn.
About the Medical Research Commercialisation Fund (MRCF) and Brandon Capital Partners
Brandon Capital Partners is a venture capital firm that manages the Medical Research Commercialisation Fund (MRCF), Australia and New Zealand’s largest life science investment fund. The MRCF is a unique collaboration between major Australian superannuation funds, the Australian and New Zealand governments, Australian state governments and more than 50 leading medical research institutes and research hospitals. The MRCF supports the development and commercialisation of early-stage biomedical discoveries originating from member research organisations, providing both capital and expertise to guide the successful development of new therapies. The MRCF has supported more than 45 start-up companies to date, most of which were founded by the MRCF.
For more information about the MRCF visit: https://www.mrcf.com.au/
For more information about Brandon Capital Partners visit: www.brandoncapital.com.au
For more information, or to arrange an interview, please contact:
1 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.
2 Nichols et al. The International Workshop on Meibomian Gland Dysfunction: Executive Summary IOVS, Special Issue 2011, Vol. 52, No. 4.