Merck & Co.’s Brunello trial has hit its primary endpoint, shedding light on the effects of a trispecific diabetic macular edema (DME) drug that the Big Pharma bought in a $3 billion takeover.
The phase 2b/3 trial compared Merck's remigromig to ranibizumab, the VEGF inhibitor that Roche’s Genentech sells as Lucentis in the U.S. Mimicking a natural ligand called norrin, remigromig agonizes the Wnt signaling pathway. The pathway supports the restoration and maintenance of blood-retinal barrier integrity, suggesting remigromig could improve visual outcomes.
Merck’s Brunello trial provided support for the hypothesis while leaving questions about remigromig’s commercial prospects unanswered. Both doses of remigromig were noninferior to ranibizumab at Week 52 on the primary endpoint, which looked at change on the best-corrected visual acuity vision test.
Remigromig was well tolerated, Merck said. However, the company reported higher rates of proliferative diabetic retinopathy, vitreous hemorrhage and treatment discontinuations because of adverse events on remigromig than on ranibizumab. Merck is running further analyses to characterize the findings. Eyebiotech, remigromig’s original developer, saw no drug-related adverse events in a phase 1b/2a trial.
Merck will present data from the trial at the American Academy of Ophthalmology Annual Meeting next month. The Big Pharma also plans to discuss the data with regulatory authorities. Another phase 2b/3 trial of remigromig in DME is ongoing and scheduled to reach primary completion in March, according to the federal trials database. Like Brunello, the second trial is comparing remigromig to ranibizumab.
At a Wells Fargo event this month, analyst Mohit Bansal questioned Merck Research Laboratories President Dean Li, M.D., Ph.D., about whether Merck believed it could show superiority to ranibizumab in the Brunello trial. Bansal framed the question in the context of the argument that Merck is “going after the weakest drug.” Lucentis competes with rival VEGF drugs, namely Regeneron’s Eylea and Roche’s Vabysmo, for the DME market.
Li said at the event that 30% to 40% of people don’t respond or stop responding to existing VEGF drugs. Remigromig is Merck’s attempt to give 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.
Merck acquired remigromig and the Tie2xVEGF bispecific, MK-8748, in its $1.3 billion upfront takeover of EyeBio in 2024. Merck is also on the hook for up to $1.7 billion in milestones. The assets are part of Merck’s efforts to grow beyond the loss of exclusivity for Keytruda.