Author(s): Martin David Harp

Key Takeaways

• MK-8748 combines direct Tie2 pathway activation with VEGF inhibition, targeting persistent vascular leakage and vessel instability implicated in ongoing vision loss despite anti-VEGF therapy alone.
• MALBEC randomizes patients 1:1:1 to two MK-8748 regimens or aflibercept 2 mg, with BCVA change from baseline to Year 1 as the primary efficacy endpoint.
• Dosing includes three monthly loading injections, then q8w through week 48, followed by response-guided individualized retreatment intervals with final assessment at week 96.
• A second wet AMD study is planned for 2026, with advancement into pivotal evaluation supported by phase 1/2a RIOJA data across wet AMD, BRVO-related macular edema, and DME.
• Merck’s retinal pipeline also includes MK-3000 (Restoret/EYE103) for DME, in the phase 2b/3 BRUNELLO trial versus ranibizumab with two intravitreal dose levels.

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.

Read more or watch the video: https://shorturl.at/LN3q6

Source: Ophthalmology Times