Boehringer Ingelheim shares positive results from the first study
worldwide in diabetic macular ischemia
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 764524BI 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
ischemiaDiabetic 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 IngelheimBoehringer 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