Merck Initiates Pivotal Phase 2b/3 Trial for Novel Bispecific Antibody MK-8748 in Wet Age-Related Macular Degeneration
核心洞察
Merck (搜索) has launched the MALBEC trial, a pivotal Phase 2b/3 study evaluating MK-8748 (Tiespectus), a novel bispecific antibody with dual Tie2 (搜索) agonist/VEGF (搜索) inhibitor mechanism for treating neovascular age-related macular degeneration (搜索).
The decision to advance to pivotal studies is based on positive results from the Phase 1/2a RIOJA trial, marking the first of a broader late-phase development program for this investigational therapy.
MK-8748 represents a differentiated approach to maintaining vascular stability in retinal diseases, potentially addressing the unmet need for patients who remain at risk of vision loss despite current available therapies.
Merck (搜索) has initiated the MALBEC trial, a pivotal Phase 2b/3 study evaluating MK-8748 (Tiespectus, EYE201), a novel investigational bispecific antibody for the treatment of neovascular (wet) age-related macular degeneration (NVAMD (搜索)). The therapy represents a differentiated approach with its dual mechanism that directly activates Tie2 (搜索) signaling while inhibiting vascular endothelial growth factor (搜索) (VEGF (搜索)).
The decision to advance MK-8748 into pivotal studies is based on results from the Phase 1/2a RIOJA trial (NCT06664502), a two-part study that evaluated the therapy in patients with NVAMD (搜索), macular edema secondary to branch retinal vein occlusion (搜索) (BRVO (搜索)), or diabetic macular edema (搜索) (DME (搜索)). MALBEC represents the first trial of a broader late-phase development program, with a second study in NVAMD scheduled to begin this year (NCT07496567).
Addressing Unmet Medical Need
"Despite available therapies, many patients with neovascular age-related macular degeneration (搜索) remain at risk of further vision loss due to continued vascular leakage," said Dr. David Guyer, founder, chief executive officer and president of EyeBio (搜索), a wholly-owned subsidiary of Merck (搜索). "With its differentiated dual mechanism directly agonizing Tie2 (搜索) and inhibiting VEGF (搜索), MK-8748 has the potential to offer a novel approach to maintain vascular stability for patients with serious retinal diseases."
Neovascular age-related macular degeneration (搜索) 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, nearly 1.5 million people are estimated to be living with late-stage AMD, including NVAMD (搜索).
Trial Design and Endpoints
MALBEC is a randomized, double-masked, pivotal Phase 2b/3 trial (NCT07440225) 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.
The treatment protocol involves participants initially receiving three monthly (Q4W) IVT administrations of MK-8748 or aflibercept, followed by treatments every 8 weeks (Q8W) 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.
Novel Dual Mechanism Approach
MK-8748 is a novel investigational bispecific antibody with a dual mechanism that directly activates the Tie2 (搜索) pathway and inhibits VEGF (搜索) 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.
Broader Ophthalmology Pipeline
Merck (搜索) is advancing an ophthalmology pipeline aimed at addressing certain retinal diseases associated with vascular leakage and neovascularization, including NVAMD (搜索), DME (搜索) and macular edema secondary to retinal vein occlusion (搜索) (RVO (搜索)). 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 (搜索) (Wnt (搜索)) signaling pathway that is being studied in two fully enrolled, ongoing registrational Phase 2b/3 studies for the treatment of DME.