On July 9, Texas Retina Associates Director of Clinical Research for Dallas Ashkan Abbey, MD, dosed the first patient in the Phase Ib LOTUS trial of EB-105, the world’s first pentavalent trispecific antibody targeting VEGF-A, VEGF-B, placental growth factor (PlGF), angiopoetin-2 (Ang-2), and interleukin-6 receptor (IL-6R) in diabetic macular edema (DME).
Understanding the Causes of Macular Edema and the Aim of EB-105
Macular edema is the build-up of fluid in the macula, which causes it to swell and thicken, distorting vision. It occurs when there is abnormal leakage and accumulation of fluid in the macula from damaged blood vessels in the nearby retina.
VEGF-A, VEGF-B, PIGF, and Ang-2 are all naturally occurring proteins that stimulate formation of blood vessels in the body, while IL-6R is a cytokine receptor responsible for controlling inflammatory responses. IL-6R is known to play a role in endothelial cell barrier dysfunction, leading to vascular leakage. EB-105 was designed and has demonstrated in preclinical studies to inhibit VEGF-A, Ang-2, and IL-6R signaling.
“Patients with DME often have persistence of intraretinal fluids even after ongoing use of available anti-VEGF treatments like aflibercept and faricimab, and we believe this is due to inflammation, including elevated levels of IL-6,” explains Dr. Abbey. “This challenge can make their condition difficult to manage. As retina specialists, we welcome the addition of new treatments that could potentially inhibit the IL-6 pathway, and it is our hope that EB-105 will translate into incremental improvements in visual acuity, durability of response, and improved drying of the retina for our patients.”
About the LOTUS Trial
The LOTUS trial is a first-in-human, open-label, multicenter, single intravitreal injection, dose-escalation study of EB-105, and Texas Retina serves as one of only four sites in the U.S. participating. The study will evaluate three dose levels of EB-105 in patients with center-involved DME and will enroll approximately 12 patients (4 per dose level). The primary objectives are to evaluate safety, tolerability and pharmacodynamics (as assessed by imaging and visual acuity assessments) and to select the two best doses for a separate repeat injection study that is planned for 2025.
For more information about participation in the LOTUS study at Texas Retina, click here to contact study coordinator Marisa Kubacki. Physicians can click here to directly refer a patient for this trial.
To learn more about all the clinical trials currently available at Texas Retina, click here.