Merck launches phase 2b/3 MALBEC trial of MK-8748 in wet AMD

Merck has initiated MALBEC, its phase 2b/3 clinical trial evaluating MK-8748 (also known as Tiespectus, EYE201) for the treatment of neovascular (wet) age-related macular degeneration (AMD).

MK-8748 is defined by the company as a “novel investigational bispecific antibody with a dual mechanism that directly activates the Tie2 pathway and inhibits VEGF with the goal of stabilizing retinal and choroidal blood vessels and reducing fluid accumulation in the macula.”

According to the company, preclinical evidence may suggest that dual pathway modulation helps improve vascular stability in the retina and supports vision preservation in patients with certain vascular retinal diseases.¹

MALBEC (NCT07440225) is a randomized, double-masked trial evaluating the safety and efficacy of MK-8748 at 2 dose levels versus control (aflibercept 2mg). The primary endpoint of the trial is mean change in best-corrected visual acuity (BCVA) from baseline to Year 1 in the study eye of the participants, using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) vision.

Patients will be randomized 1:1:1 to receive 2-dose regimens of MK-8748 or aflibercept 2mg. Patients will initially receive 3 monthly doses of MK-8748 or aflibercept 2mg. These doses will be followed by treatments every 8 weeks until week 48. Following week 48, patients will be treated at intervals determined based on individualized response to treatment, with the last study visit at week 96.

David Guyer, MD, founder, CEO and president of EyeBio, commented on the trial in a press release from the company, saying, “Despite available therapies, many patients with neovascular age-related macular degeneration remain at risk of further vision loss due to continued vascular leakage. 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.”

In addition to MALBEC, the company intends to initiate a second study in wet AMD in 2026 (NCT07496567). The company noted that the plan to advance into pivotal studies is based on results from the Phase 1/2a RIOJA trial (NCT06664502), which was a 2-part study evaluating MK-8748 in patients with either wet AMD, macular edema secondary to branch retinal vein occlusion (BRVO), or diabetic macular edema (DME).

In addition to MK-8748, Merck is developing MK-3000 (also known as Restoret, EYE103) for the treatment of DME. MK-3000 is currently being evaluated in the BRUNELLO trial, a randomized, double-masked trial evaluating the efficacy and safety of 2 dose levels of intravitreal MK-3000 versus active control ranibizumab.²

References:

1. Merck announces initiation of pivotal phase 2b/3 trial evaluating MK-8748 (Tiespectus), an investigational bispecific Tie2 Agonist/VEGF inhibitor, for the treatment of neovascular age-related macular degeneration. Published April 2, 2026. Accessed April 6, 2026. https://www.businesswire.com/news/home/20260401721827/en/Merck-Announces-Initiation-of-Pivotal-Phase-2b3-Trial-Evaluating-MK-8748-Tiespectus-an-Investigational-Bispecific-Tie2-AgonistVEGF-Inhibitor-for-the-Treatment-of-Neovascular-Age-Related-Macular-Degeneration

2. Harp MD. Merck and EyeBio announce initiation of phase 2b/3 BRUNELLO trial evaluating MK-3000 for treatment of diabetic macular edema. Published September 5, 2024. Accessed April 6, 2026. https://www.ophthalmologytimes.com/view/merck-and-eyebio-announce-initiation-of-phase-2b-3-brunello-trial-evaluating-mk-3000-for-treatment-of-diabetic-macular-edema