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
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
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bispecific antibodymedical
A bispecific antibody is a specially designed protein that can attach to two different targets at the same time. Think of it as a custom-made connector that brings two things together—such as a disease cell and an immune system component—helping the body fight illnesses more effectively. For investors, understanding bispecific antibodies is important because they represent innovative therapies that could lead to new treatments and potentially lucrative market opportunities.
tie2medical
Tie2 is a protein receptor found on cells that line blood vessels that acts like a control switch for vessel stability, growth and leakage. Drugs that turn this switch on or off can tighten or loosen blood vessels, which matters to investors because therapies targeting Tie2 are central to treatments for cancer, eye and vascular diseases; success or failure in this area can affect a drug candidate’s value and a biotech’s prospects.
vegfmedical
Vascular endothelial growth factor (VEGF) is a naturally occurring protein that signals the body to grow new blood vessels, like a fertilizer prompts plants to sprout. It matters to investors because drugs that block or mimic VEGF can dramatically change outcomes for cancers and eye diseases, making them major drivers of clinical trial results, regulatory approvals, market value and future revenue potential for biopharma companies.
A progressive eye disease in older adults where abnormal blood vessels grow beneath the central retina and leak fluid or blood, quickly damaging sharp central vision used for reading and recognizing faces. For investors, it matters because it creates ongoing demand for medical treatments, diagnostics and follow-up care, and outcomes hinge on clinical trial results, regulatory approvals and reimbursement decisions that can sharply affect the value of companies developing therapies — like a chronic market need driven by a high-impact illness.
diabetic macular edemamedical
Diabetic macular edema is an eye condition in which fluid leaks into and swells the macula, the part of the retina used for sharp, central vision, often as a complication of diabetes. For investors it matters because it drives demand for medicines, medical devices and eye-care services, influences clinical trial and regulatory outcomes, and can affect healthcare costs and revenue forecasts—think of the macula as the camera’s central lens that becomes blurred when it soaks up excess fluid.
retinal vein occlusionmedical
Retinal vein occlusion is a blockage of one of the small veins that drain blood from the light-sensitive layer at the back of the eye, like a clogged pipe causing fluid and pressure to build up and damaging vision. For investors it matters because the condition drives demand for drugs, medical devices and procedures, influences clinical trial activity and regulatory decisions, and can materially affect revenue prospects for companies developing treatments or diagnostics.
wnt signaling pathwaymedical
A cellular communication network that tells cells when to grow, divide, move or specialize, much like a traffic signal system that coordinates cars at intersections. It matters to investors because drugs or diagnostics that modify this pathway can lead to treatments for cancer, developmental disorders, or tissue repair, affecting a company’s drug pipeline, regulatory risk and long-term revenue prospects.
phase 2b/3medical
A phase 2b/3 trial is a combined late-stage clinical study that first refines the best dose and measures how well a treatment works (phase 2b) then expands to a larger, definitive test of safety and effectiveness needed for regulatory approval (phase 3). For investors, results from a phase 2b/3 act like a dress rehearsal that turns into opening night: positive, well-controlled outcomes substantially raise the chance of approval and future sales, while failures can sharply reduce a drug’s value.
RAHWAY, N.J.--(BUSINESS WIRE)--
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the initiation of a pivotal Phase 2b/3 trial evaluating MK-8748 (also known as Tiespectus, EYE201), a novel investigational bispecific antibody that directly activates Tie2 signaling and inhibits vascular endothelial growth factor (VEGF), for the treatment of neovascular (wet) age-related macular degeneration (NVAMD).
The study, known as MALBEC, is the first trial of a broader late-phase development program for MK-8748, with a second study in NVAMD scheduled to begin this year (NCT07496567). The decision to advance into pivotal studies is based on results from the Phase 1/2a RIOJA trial (NCT06664502), a two-part study evaluating MK-8748 in patients with either NVAMD, macular edema secondary to branch retinal vein occlusion (BRVO) or diabetic macular edema (DME).
“Despite available therapies, many patients with neovascular age-related macular degeneration remain at risk of further vision loss due to continued vascular leakage,” said Dr. David Guyer, founder, chief executive officer and president, EyeBio, a wholly-owned subsidiary of Merck & Co., Inc., Rahway, N.J., USA. “With its differentiated dual mechanism directly agonizing Tie2 and inhibiting VEGF, MK-8748 has the potential to offer a novel approach to maintain vascular stability for patients with serious retinal diseases.”
Merck is advancing an ophthalmology pipeline aimed at addressing certain retinal diseases associated with vascular leakage and neovascularization, including NVAMD, DME and macular edema secondary to retinal vein occlusion (RVO). In addition to MK-8748, the company is developing MK-3000 (also known as Restoret, EYE103), an investigational, potentially first-in-class tetravalent, tri-specific antibody that activates the Wingless-related integration site (Wnt) signaling pathway that is being studied in two fully enrolled, ongoing registrational Phase 2b/3 studies for the treatment of DME.
About the MALBEC trial
MALBEC is a randomized, double-masked, pivotal Phase 2b/3 trial (NCT07440225) evaluating the safety and efficacy of two dose levels of intravitreal (IVT) MK-8748 versus active control aflibercept 2mg. Eligible patients will be randomized 1:1:1 to receive two dose regimens of MK-8748 or aflibercept 2mg; participants will initially receive three monthly (Q4W) IVT administrations of MK-8748 or aflibercept, 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. The primary endpoint 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. For further information about the MALBEC trial, please visit www.clinicaltrials.gov.
About neovascular age-related macular degeneration
Neovascular (wet) age-related macular degeneration (NVAMD) is the most common cause of vision loss among older adults, caused by the growth of abnormal blood vessels under the retina. In the United States, it is estimated that nearly 1.5 million people are living with late-stage AMD, including NVAMD.
About MK-8748
MK-8748 (also known as Tiespectus, EYE201) is 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. Preclinical and early clinical evidence indicate that dual pathway modulation may help improve vascular stability in the retina and support vision preservation in patients with certain vascular retinal diseases. MK-8748 is currently being studied in a pivotal Phase 2b/3 trial for the treatment of NVAMD, with a second study scheduled to begin this year.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
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