Advancing a Vision for Pioneering Treatments in Diabetic Macular Ischemia

We live in a visual world. From the moment we wake up and look at the clock, through a workday of screen time and video calls, to an evening of meeting friends or watching TV. But for millions of people around the world with diabetic retinopathy – a leading cause of visual impairment and blindness in the working population,¹ their world looks very different. Diabetic retinopathy (DR)² is a condition which affects around a third of those living with diabetes. At least 7% of those with DR also have Diabetic Macular Ischemia (DMI), a not yet fully understood complication of DR, which can lead to irreversible vision loss. Boehringer Ingelheim scientists are taking a paradigm-shifting approach, aiming to advance breakthrough therapies that preserve and restore vision in people with DMI.

DMI is caused by a decrease in blood flow (ischemia) to the macula, the part of the retina responsible for central and color vision as well as sharp vision that enables us to see fine details. As damage to the retina progresses, small blood vessels in the macula may close off completely, inducing ischemia and starving the macula of oxygen and nutrients. The foveal avascular zone (FAZ), which is in the center of the macula, is enlarged in those with DMI, indicating the progression of ischemia. Our goal is to achieve revascularization of the retina, including the macula, by guiding the new vessels into the ischemic tissue to reduce and/or prevent further retinal damage. This in turn will allow the patient to retain their vision.

First-in-Human Trial

At Boehringer Ingelheim, we are one of the few research groups focusing on DMI. Currently there are no available treatments to prevent either the onset or progression of DMI, and our scientists are working hard to change this. They are focusing their pioneering research on preserving and/or restoring vascular function with ischemic modulators, advancing a first-in-class agent to early clinical development. Our ambition is to shape the therapeutic landscape for people living with DMI and offer treatment options to address their vision loss.

Pre-clinical studies of an ischemia modulator (BI-X) demonstrated improvements in ischemia, thus supporting the initiation of clinical trials.³ Preliminary results from the Phase I HORNBILL study (ClinicalTrials.gov Identifier: NCT04424290), presented at the recent Association for Research in Vision and Ophthalmology (ARVO) 2021 meeting,⁴ showed single doses of BI-X were well-tolerated. Neither dose-limiting events, nor serious adverse events or any drug related adverse events have been reported to date. A Phase II study will examine the efficacy of BI-X in patients with DMI in a double masked randomized controlled trial. There are also further promising compounds with potential to treat DMI at different stages in our pipeline.

“By discovering molecules that safely and effectively combat retinal ischemia, we will provide breakthrough treatment options to patients that will significantly impact their lives” explains Remko Bakker, Director CardioMetabolic Diseases Research at Boehringer Ingelheim.

Increasing Understanding about DMI

In addition to being the first to bring a potential treatment for DMI to clinical trials, we recognize the need to improve knowledge and support improved diagnosis. Diagnosis of DMI is challenging for clinicians and scientists. It requires the intravenous injection of fluorescein dye directly into the back of the eye to measure the size of the foveal avascular zone (FAZ). Recent advances have resulted in a new non-invasive imaging technique called optical coherence tomography angiography (OCTA). This uses laser light reflection to accurately visualize the retinal microvasculature in just a few seconds.

Our team is building one of the largest prospective OCTA datasets in people with diabetic retinopathy. This will help to increase understanding of the real prevalence of DMI and identify patients most at risk of imminent vision loss.

“The improvement of DR screening, treatment of diabetic macular edema and vitreoretinal surgery has significantly reduced DR related blindness in recent years” says Victor Chong, Global Head of Medicine, Retinal Health at Boehringer Ingelheim. “However, despite these improvements, people with diabetes still experience vision loss as a result of DMI. Our goal is to address the significant need for effective treatments for DMI and we aim to eventually eliminate blindness from people with diabetic retinopathy.”

References:

¹ Wong TY, Sabanayagam C. Strategies to Tackle the Global Burden of Diabetic Retinopathy: From Epidemiology to Artificial Intelligence. Ophthalmologica. 2020;243(1):9–20
² IDF Diabetes Atlas | 9th edition https://www.diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf#page=38&zoom=auto
³ L Thomas et al. In vitro and in vivo studies of BI-X: A humanised Sema3A antibody. ARVO 2021 Poster presentation #3542620 https://arvo2021.arvo.org/meetings/virtual/ZWRLcEqi3ht42YcW7
⁴ Quan D. Nguyen et al. The HORNBILL study: A Phase I/IIa trial examining the safety of BI-X in patients with diabetic macular ischemia and diabetic retinopathy treated with pan-retinal photocoagulation. ARVO 2021 Oral presentation #3529174 https://arvo2021.arvo.org/meetings/virtual/discW3dqEZuGyzF5L

Image credit:

Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=29025015

OIRRC Reading Center