Dual Tie2/VEGF mechanism may ease wet AMD injection burden

Not every patient with wet age-related macular degeneration (AMD) responds fully to anti-VEGF monotherapy. Jonathan Gloth, MD, a retina specialist at InVision EyeCare in Lakewood, NJ said a subset of patients never achieve a completely dry retina, or cannot extend beyond monthly injections, despite ongoing treatment. He said Tie2 pathway agonism, the mechanism behind the investigational bispecific antibody MK-8748 (Tiespectus; EyeBio/Merck), offers "a way to get more stabilization of the vasculature" for these patients.

Gloth compared the safety profile of Tie2-targeted approaches with intravitreal steroids, which also reduce vascular permeability but carry a risk of elevated intraocular pressure (IOP). He said IOP elevation has not emerged as a signal in early MK-8748 trials.

Reducing the clinical cost of missed and delayed doses

Undertreatment and missed injections remain common in real-world wet AMD care, and Gloth said a therapy that extends the durability of vascular stabilization could decrease the clinical consequences of a delayed dose. "Many patients wind up in the hospital, they have a fall, and they're 4, 6, 8 weeks late for their next injection. If that patient is receiving a new, novel treatment that, you know, perhaps stabilizes the vasculature for an extra month or two, that's going to make a huge difference.”

Gloth said the broader shift toward therapies that combine VEGF inhibition with a second vascular-stabilizing mechanism marks a meaningful advance for wet AMD, retinal vein occlusion, and diabetic macular edema, since each of those diseases is driven by vascular leakage.

If a dual Tie2/VEGF mechanism performs as intended in pivotal trials, Gloth said it could change how retina specialists counsel patients about their long-term outlook. Rather than committing patients to indefinite monthly visits, he said such a therapy could let specialists offer a more positive outlook built around longer intervals between injections while maintaining vision. MK-8748 is under evaluation in the pivotal phase 2b/3 MALBEC (NCT07440225) and TORRONTES (NCT07496567) trials, each comparing 2 dose regimens of MK-8748 with aflibercept 2 mg (Eylea; Regeneron) in patients with wet AMD.1

Reference
1. Merck & Co, Inc. 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. News release. Merck & Co, Inc; April 2, 2026. Accessed August 24, 2026.