- Initiation of pivotal Phase 2b/3 MALBEC trial of MK-8748 (Tiespectus, EYE201), a bispecific Tie2 agonist/VEGF inhibitor, for neovascular AMD.
- MALBEC randomizes patients 1:1:1 to two MK-8748 dose regimens or aflibercept 2 mg, with intravitreal dosing Q4W for three doses then Q8W through week 48 and the last visit at week 96.
- Primary endpoint is mean change in best-corrected visual acuity (BCVA) from baseline to Year 1 using ETDRS.
- A second pivotal NVAMD study (NCT07496567) is planned this year; advancement to pivotal studies was based on Phase 1/2a RIOJA data (NCT06664502), and Merck is also running registrational Phase 2b/3 trials of MK-3000 (Restoret, EYE103) for DME.
Trial initiation
Merck has initiated the pivotal Phase 2b/3 MALBEC trial of MK-8748 (Tiespectus, EYE201), a bispecific Tie2 agonist/VEGF inhibitor, for neovascular AMD; a second pivotal NVAMD study is planned this year and progression to pivotal studies was based on Phase 1/2a RIOJA (NCT06664502) results.
MALBEC design
MALBEC (NCT07440225) is a randomized, double-masked 1:1:1 study comparing two intravitreal MK-8748 dose regimens to aflibercept 2 mg; dosing is three monthly (Q4W) injections then every 8 weeks (Q8W) through week 48, with individualized intervals thereafter and the last visit at week 96; primary endpoint is mean change in best-corrected visual acuity (BCVA) at Year 1 using ETDRS.
MK-8748 mechanism
MK-8748 is a bispecific antibody that directly activates Tie2 signaling while inhibiting VEGF, intended to stabilize retinal and choroidal vessels and reduce macular fluid; preclinical and early clinical data support dual-pathway modulation for vascular stability.
Other pipeline programs
Merck is also developing MK-3000 (Restoret, EYE103), a tetravalent tri-specific antibody that activates Wnt signaling, currently in two fully enrolled registrational Phase 2b/3 trials for diabetic macular edema (DME).
Disease context
Neovascular AMD is a leading cause of vision loss in older adults; about 1.5 million people in the U.S. are estimated to have late-stage AMD, including NVAMD.
