Merck announced the initiation of a pivotal Phase 2b/3 trial evaluating MK-8748 (also known as Tiespectus, EYE201), a novel investigational bispecific antibody that directly activates Tie2 signaling and inhibits vascular endothelial growth factor (VEGF), for the treatment of neovascular (wet) age-related macular degeneration (NVAMD). The study, known as MALBEC, is the first trial of a broader late-phase development program for MK-8748, with a second study in NVAMD scheduled to begin this year. The decision to advance into pivotal studies is based on results from the Phase 1/2a RIOJA trial, a two-part study evaluating MK-8748 in patients with either NVAMD, macular edema secondary to branch retinal vein occlusion (BRVO) or diabetic macular edema (DME).
Merck is advancing an ophthalmology pipeline aimed at addressing certain retinal diseases associated with vascular leakage and neovascularization, including NVAMD, DME and macular edema secondary to retinal vein occlusion (RVO). In addition to MK-8748, the company is developing MK-3000 (also known as Restoret, EYE103), an investigational, potentially first-in-class tetravalent, tri-specific antibody that activates the Wingless-related integration site (Wnt) signaling pathway that is being studied in two fully enrolled, ongoing registrational Phase 2b/3 studies for the treatment of DME. MALBEC is a randomized, double-masked, pivotal Phase 2b/3 trial evaluating the safety and efficacy of two dose levels of intravitreal (IVT) MK-8748 versus active control aflibercept 2mg.
Eligible patients will be randomized 1:1:1 to receive two dose regimens of MK-8748 or aflibercept 2mg; participants will initially receive three monthly IVT administrations of MK-8748 or aflibercept, followed by treatments every 8 weeks until week 48. After week 48, participants will be treated at intervals determined based on individualized response to treatment, with the last study visit at week 96. The primary endpoint 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.
Neovascular (wet) age-related macular degeneration (NVAMD) is the most common cause of vision loss among older adults, caused by the growth of abnormal blood vessels under the retina. In the United States, it is estimated that nearly 1,500,000 people are living with late-stage AMD, including NVAMD. MK-8748 (also known as Tiespectus, EYE201) is 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.
Preclinical and early clinical evidence indicate that dual pathway modulation may help improve vascular stability in the retina and support vision preservation in patients with certain vascular retinal diseases. MK-8748 is currently being studied in a pivotal Phase 2b/3 trial for the treatment of NVAMD, with a second study scheduled to begin this year.
