Merck Advances MK-8748 Into Late-Stage Trials for Wet AMD

Merck Advances MK-8748 Into Late-Stage Trials for Wet AMD

By, Admin 6 April 2026

Global pharmaceutical leader Merck & Co., Inc. has initiated a pivotal Phase 2b/3 clinical trial to evaluate MK-8748 (also known as Tiespectus, EYE201), an investigational bispecific antibody for the treatment of neovascular (wet) age-related macular degeneration (NVAMD).

This move marks a significant step forward in Merck’s ophthalmology pipeline, particularly in addressing retinal diseases linked to vascular leakage and abnormal blood vessel growth.

A New Approach to Treating Wet AMD

MK-8748 stands out due to its dual mechanism of action, designed to tackle the root causes of retinal damage:

  • Activates the Tie2 signalling pathway, improving vascular stability
  • Inhibits vascular endothelial growth factor (VEGF), reducing abnormal blood vessel growth

This combined approach aims to stabilize retinal and choroidal blood vessels while reducing fluid buildup in the macula—two critical factors in preserving vision.

The MALBEC Trial: Study Design and Objectives

The newly initiated study, known as the MALBEC trial, is the first in a broader late-stage development program for MK-8748.

Here’s how the trial is structured:

  • Type: Randomized, double-masked Phase 2b/3 trial
  • Participants: Patients with NVAMD
  • Treatment arms:
    • Two dose levels of MK-8748
    • Active comparator: aflibercept 2mg
  • Dosing schedule:
    • Initial three monthly intravitreal injections (Q4W)
    • Followed by dosing every 8 weeks (Q8W) until week 48
    • Post-week 48: individualized treatment intervals
  • Duration: Up to 96 weeks
  • Primary endpoint:
    • Mean change in best-corrected visual acuity (BCVA) at one year

A second late-stage study in NVAMD is also expected to begin later this year, further strengthening the clinical program.

Backed by Early Clinical Evidence

The decision to advance MK-8748 into pivotal trials is supported by results from the Phase 1/2a RIOJA trial, which evaluated the therapy across multiple retinal conditions, including:

  • NVAMD
  • Diabetic macular edema (DME)
  • Macular edema following branch retinal vein occlusion (BRVO)

These early findings suggest that dual pathway targeting may improve vascular stability and support long-term vision outcomes.

Expert Perspective

David Guyer, founder and CEO of EyeBio (a wholly owned subsidiary of Merck), highlighted the unmet need in NVAMD treatment:

Many patients remain at risk of vision loss due to ongoing vascular leakage despite existing therapies.

He emphasized that MK-8748’s dual mechanism could offer a novel and differentiated approach to maintaining retinal health.

Expanding Merck’s Ophthalmology Pipeline

Beyond MK-8748, Merck is actively building a pipeline targeting retinal diseases such as:

  • NVAMD
  • Diabetic macular edema
  • Retinal vein occlusion-related macular edema

Another key candidate is MK-3000 (Restoret, EYE103), a tri-specific antibody designed to activate the Wnt signalling pathway. It is currently being evaluated in ongoing Phase 2b/3 studies for DME.

Understanding the Disease Burden

Neovascular (wet) age-related macular degeneration is a leading cause of vision loss among older adults. It occurs due to the growth of abnormal blood vessels beneath the retina, leading to leakage, swelling, and progressive damage.

In the United States alone, approximately 1.5 million people are estimated to be living with late-stage AMD, including NVAMD.

What This Means Going Forward?

Merck’s advancement of MK-8748 into late-stage trials reflects a broader shift toward next-generation biologics in ophthalmology—therapies designed not just to manage symptoms, but to target multiple disease pathways simultaneously.

If successful, MK-8748 could:

  • Offer improved durability over existing anti-VEGF therapies
  • Reduce treatment burden through less frequent dosing
  • Provide better long-term vision outcomes

Conclusion

With the initiation of the MALBEC trial, Merck is doubling down on innovation in retinal disease treatment. MK-8748’s dual mechanism positions it as a potentially transformative therapy in the NVAMD landscape, where unmet needs remain high despite current treatment options.

The next phase of clinical data will be critical in determining whether this approach can redefine the standard of care in wet AMD.

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!