Merck, known as MSD outside the United States and Canada, has announced the initiation of a pivotal Phase 2b/3 clinical trial evaluating MK-8748 (Tiespectus, EYE201) for the treatment of neovascular (wet) age-related macular degeneration (NVAMD).
The investigational therapy is a bispecific antibody designed to activate Tie2 signaling while simultaneously inhibiting vascular endothelial growth factor (VEGF). By targeting these two pathways, the therapy aims to improve vascular stability and reduce leakage, which are key drivers of vision loss in retinal diseases.
MALBEC Study Marks Start of Late-Phase Development
The newly launched MALBEC trial represents the first study in a broader late-phase development program for MK-8748. Additionally, Merck plans to initiate a second Phase 2b/3 trial in NVAMD later this year (NCT07496567).
As per the Merck Press release, the company decided to advance the therapy into pivotal studies following encouraging results from the Phase 1/2a RIOJA trial (NCT06664502). This earlier two-part study evaluated MK-8748 in patients with neovascular age-related macular degeneration, diabetic macular edema (DME), and macular edema caused by branch retinal vein occlusion (BRVO).
Dual-Mechanism Approach May Improve Retinal Vascular Stability
According to Dr. David Guyer, Founder, CEO, and President of EyeBio, a wholly owned subsidiary of Merck, many patients with wet age-related macular degeneration continue to face the risk of vision loss despite currently available treatments.
He noted that the dual mechanism of MK-8748—directly activating Tie2 while inhibiting VEGF—may provide a differentiated therapeutic strategy. This approach could help maintain vascular stability and reduce leakage in patients with serious retinal diseases.
Expanding Merck’s Ophthalmology Pipeline
Meanwhile, Merck continues to expand its ophthalmology research pipeline to address retinal diseases linked to vascular leakage and abnormal blood vessel growth. These conditions include neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion (RVO).
In addition to MK-8748, the company is also developing MK-3000 (Restoret, EYE103). This investigational therapy is a potentially first-in-class tetravalent, tri-specific antibody designed to activate the Wingless-related integration site (Wnt) signaling pathway.
Currently, MK-3000 is being evaluated in two fully enrolled registrational Phase 2b/3 clinical trials for diabetic macular edema, highlighting Merck’s broader strategy to advance innovative therapies for retinal vascular diseases.