Merck & Co. recently announced the initiation of a pivotal phase 2b/3 trial evaluating MK-8748 (also known as TIESPECTUS, EYE201) for the treatment of neovascular age-related macular degeneration (nAMD).
Let’s start with Merck.
The Germany-based Merck Group is a multinational pharmaceutical giant with U.S. headquarters located in Rahway, New Jersey.
Important to note: While extensive in its product offerings, until recently the company had no prior investments within the ophthalmic industry—instead focusing primarily on oncology and cardiovascular.
And when did that change?
If you may recall, Merck began a major ophthalmic expansion in 2024 with the acquisition of Eyebiotech Limited (EyeBio), making the biotech company a wholly-owned subsidiary of Merck.
Quick reminder: EyeBio is a United Kingdom-based, privately held ophthalmology biotechnology company developing therapies for ocular diseases.
- Most notable of these candidates: RESTORET (EYE103, MK-3000), a tri-specific antibody targeting the wingless-related integration site (Wnt) pathway.
Tell me about RESTORET.
RESTORET was EyeBio’s lead asset and is currently in clinical development for the treatment of retinal diseases characterized by vascular leakage via intravitreal (IVT) injection.
The drug is being studied in two ongoing registrational phase 2b/3 studies (BAROLO [NCT06957080] and BRUNELLO [NCT06571045]) for the treatment of diabetic macular edema (DME)—but more on those later.
So where does that nAMD candidate come in?
While RESTORET may be EyeBio’s lead asset, its retinal disease-focus pipeline also includes TIESPECTUS (MK-8748)—the topic of our story today.
With that out of the way, let’s dig into TIESPECTUS.
TIESPECTUS is a novel investigational bispecific antibody.
- What it does: Directly activates Tie2 signaling and inhibits vascular endothelial growth factor (VEGF)
- How it works: A dual mechanism stabilizes retinal and choroidal blood vessels, thereby eliminating macular fluid in retinal vascular disease.
- Its investigational indications: nAMD and macular edema secondary to branch retinal vein occlusion (BRVO).
Where is it in the clinical development process?
There are currently two ongoing (and one upcoming) clinical studies on TIESPECTUS, including:
- RIOJA (NCT06664502): Ongoing phase 1/2a two-part trial evaluating the drug in patients with nAMD, macular edema secondary to BRVO, or diabetic macular edema (DME)
- Part one: Multiple ascending dose (MAD) portion of study assessing increasing doses in ~12 participants with BRVO.
- Part two: Dose finding part with two doses of the drug being selected and their effectiveness will be compared in ~80 patients with DME or nAMD
- MALBEC (NCT07440225): Ongoing phase 2/3 trial evaluating safety and efficacy compared to aflibercept 2 mg in participants with nAMD that is recruiting
- MK-8748-003 (NCT07496567): Upcoming pivotal phase 2/3 trial with a very similar setup to MALBEC comparing MK-8748 to aflibercept 2 mg
Focusing on MALBEC … how is it setup?
Eligible patients will be randomized 1:1:1 to receive either low or high dose regiments of MK-8748 or aflibercept 2 mg.
The dosing schedule: Participants will initially receive three monthly (Q4W) intravitreal (IVT) administrations of TIESPECTUS or aflibercept 2 mg 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.
And the outcome measures?
The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to Year 1 in the study eye of the participants, using standardized Early Treatment Diabetic Retinopathy Scale (ETDRS) vision.
Plus: Secondary outcome measures include:
- Mean change in BCVA (ETDRS) letters from Day 1 over time to Year 1
- Proportion of participants who gain ≥5, ≥10, or ≥15 ETDRS letters at Year 1
- Proportion of participants who lose ≥5, ≥10, or ≥15 ETDRS letters at Year 1
- Mean change in spectral domain optical coherence tomography (SD-OCT) central subfield thickness (CST) from Day 1 to Year 1
- Number of participants who experience one or more systemic adverse events (AEs)
- Number of participants who experience one or more ocular AEs
When is MALBEC expected to end?
The estimated primary completion date is June 20, 2028.
Anything else to know?
Merck noted that the decision to advance into pivotal studies was based on results from the phase 1/2a RIOJA trial.
And those results: In October 2025, clinical data from part one of the RIOJA trial was presented at Eyecelerator in the American Academy of Ophthalmology (AAO) annual meeting, demonstrating a mean gain of 16.7 letters in BCVA and a mean CST reduction of 157.8 μm at 12 weeks.
- Plus: No serious adverse events or dose-limiting toxicity was reported.
So what’s the plan moving forward?
For TIESPECTUS: With part one of RIOJA likely ending soon (considering its estimated completion date is April 30, 2026) and MALBEC underway, Merck will undoubtedly be unveiling more data this year.
And for RESTORET: Two registrational phase 2/3 studies (BAROLO and BRUNELLO) have completed enrollment with estimated primary completion dates of March 1, 2027, and September 2026, respectively.
- To top it off: The SUPER TUSCAN phase 2 study (NCT07205887) on RESTORET for nAMD or macular edema following BRVO is currently recruiting.
Stay tuned for updates on these trials …