Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1­

DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4­ It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI.

The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1

“The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of,  and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.”

“Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.”

HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration.

About the HORNBILL study

The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year.

Notes to Editors:

About the trial (NCT04424290)

This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1

Single rising dose part

In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1

Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1

Multiple dosing part

In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1

Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1

At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change.

About BI 764524
BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions.

About diabetic retinopathy and diabetic macular ischemia
Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss.

About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at www.boehringer-ingelheim.com

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References

1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959

2 Marques IP, et al. Diabetes 2019;68:648–653

3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360

4 Tey KY, et al. Eye Vis (Lond) 2019;6:37

5 Ip MS, et al. Ophthalmology 2014;122:367–374