Merck is stepping up its fight against one of the leading causes of vision loss, launching a pivotal late-stage trial for a next-generation eye disease therapy that could reshape treatment for millions.

 

The pharmaceutical powerhouse, known as MSD outside the United States and Canada, announced it has begun a Phase 2b/3 study of MK-8748—also called Tiespectus—a novel bispecific antibody designed to tackle neovascular (wet) age-related macular degeneration (NVAMD) through a dual-action approach.

 

The trial, dubbed MALBEC, marks the first in a broader late-phase development push for MK-8748, with a second NVAMD study expected to begin later this year. The move follows encouraging early data from the Phase 1/2a RIOJA trial, which tested the therapy across multiple retinal diseases, including NVAMD, diabetic macular edema, and macular edema linked to retinal vein occlusion.

 

“Despite available therapies, many patients with neovascular age-related macular degeneration remain at risk of further vision loss due to continued vascular leakage,” said Dr. David Guyer, founder, chief executive officer and president, EyeBio, a wholly-owned subsidiary of Merck & Co. 

 

“With its differentiated dual mechanism directly agonizing Tie2 and inhibiting VEGF, MK-8748 has the potential to offer a novel approach to maintain vascular stability for patients with serious retinal diseases.”

 

MK-8748 is designed to do what current treatments struggle to achieve consistently: stabilize fragile blood vessels in the eye while reducing fluid buildup that can damage vision. By simultaneously activating the Tie2 pathway and blocking VEGF, the drug aims to address the underlying drivers of disease more effectively.

 

The MALBEC study will directly compare two dosing regimens of MK-8748 against aflibercept, a widely used standard-of-care treatment. Patients will initially receive monthly injections before moving to less frequent dosing, with outcomes tracked over nearly two years. The primary goal is to measure improvements in vision using standardized eye chart testing after one year.

 

The trial is part of a broader ophthalmology strategy at Merck targeting diseases driven by vascular leakage and abnormal blood vessel growth, including NVAMD, diabetic macular edema, and retinal vein occlusion. Alongside MK-8748, the company is advancing another experimental therapy, MK-3000, which targets a different biological pathway and is already in late-stage studies.

 

NVAMD remains a major public health challenge, particularly among older adults. The condition is caused by the growth of abnormal blood vessels beneath the retina, leading to leakage, scarring, and progressive vision loss.