Merck's trispecific remigromig matches ranibizumab in phase 2b/3 diabetic macular edema trial
核心洞察
Merck's remigromig (搜索) met the primary endpoint in the Brunello phase 2b/3 trial, showing noninferiority to ranibizumab on best-corrected visual acuity at Week 52.
The trispecific drug agonizes the Wnt signaling pathway (搜索) by mimicking norrin (搜索), offering a non-VEGF (搜索) mechanism for diabetic macular edema (搜索) patients.
Remigromig (搜索) was well tolerated, but proliferative diabetic retinopathy (搜索), vitreous hemorrhage (搜索) and adverse event-related discontinuations occurred more often than with ranibizumab.
Merck & Co. (搜索)'s remigromig (搜索) met the primary endpoint in the Brunello phase 2b/3 trial in diabetic macular edema (搜索) (DME), with both doses proving noninferior to ranibizumab at Week 52 on change in best-corrected visual acuity. The readout supports a drug that engages a different biological pathway than the VEGF (搜索) inhibitors that dominate the DME market.
Remigromig (搜索) is a trispecific designed to mimic a natural ligand called norrin (搜索) and agonize the Wnt signaling pathway (搜索), which supports the restoration and maintenance of blood-retinal barrier integrity. Merck's drug is intended to repair the retina's leaky blood-vessel barrier and reduce the swelling that blurs vision in DME, a condition in which fluid builds up in the macula, the central part of the retina, and which can lead to blindness.
Trial design and comparator
Brunello compared remigromig (搜索) with ranibizumab, the VEGF (搜索) inhibitor Roche's Genentech sells as Lucentis in the U.S. The primary endpoint assessed mean change from baseline in best-corrected visual acuity, a measure of the sharpest vision achievable with corrective lenses, in adults with DME.
Merck said remigromig (搜索) was well tolerated. However, the company reported higher rates of proliferative diabetic retinopathy (搜索), vitreous hemorrhage (搜索) and treatment discontinuations because of adverse events on remigromig than on ranibizumab. Merck is running further analyses to characterize those findings. Eyebiotech, remigromig's original developer, saw no drug-related adverse events in a phase 1b/2a trial.
"This is the first and only new mechanism of action in 20 years that has achieved Phase 3 results non-inferior to anti-VEGF (搜索) therapy, representing an important milestone for patients in developing a potential new treatment," said David Guyer, CEO of EyeBio (搜索), a wholly owned subsidiary of Merck.
Positioning against VEGF therapies
Merck Research Laboratories President Dean Li, M.D., Ph.D., said 30% to 40% of people do not respond or stop responding to existing VEGF (搜索) drugs. Remigromig (搜索) is Merck's attempt to offer those DME patients a drug that engages a different pathway. Merck, which is also developing a Tie2xVEGF bispecific, expects ophthalmologists to "mix and match" VEGF and non-VEGF treatments, Li said.
Lucentis competes with rival VEGF (搜索) drugs, namely Regeneron's Eylea and Roche's Vabysmo, for the DME market. Common treatments for the condition include anti-VEGF eye injections such as ranibizumab, which block or regulate the formation and growth of blood vessels, as well as laser therapy and steroid injections or implants.
Roughly 5.5% of all people with diabetes worldwide are affected by DME, according to National Institutes of Health data.
Next steps
Merck will present data from Brunello at the American Academy of Ophthalmology Annual Meeting next month and plans to discuss the data with regulatory authorities. A second phase 2b/3 trial of remigromig (搜索) in DME is ongoing and scheduled to reach primary completion in March, according to the federal trials database. Like Brunello, that trial is comparing remigromig with ranibizumab.
Merck acquired remigromig (搜索) and the Tie2xVEGF bispecific, MK-8748, in its $1.3 billion upfront takeover of EyeBio (搜索) in 2024, with up to $1.7 billion in milestones. The assets are part of Merck's efforts to grow beyond the loss of exclusivity for Keytruda.