Trial Success & Key Visual Acuity Results
Merck & Co.’s Brunello trial has achieved its primary endpoint, offering more clues to the impact of a trio of diabetic macular edema (DME) drugs acquired by the Big Pharma in a $3 billion takeover.
Remigromig mimics a natural molecule called norrin and agonizes the Wnt signaling pathway, whereas ranibizumab, sold in the U.S. by Genentech as Lucentis, agonizes the VEGF pathway. The pathway is involved in the maintenance and integrity of the blood-retinal barrier, indicating that remigromig may have a beneficial effect on visual outcome.
While Merck’s Brunello trial supported the hypothesis, there was no resolution as to remigromig’s commercial prospects. The primary endpoint was whether the best-corrected visual acuity test for both doses of remigromig was noninferior to ranibizumab at Week 52.
Safety Profile & Next Steps
Remigromig was found to be well tolerated, Merck said. The firm did disclose a greater incidence of other adverse events that led to higher rates of proliferative diabetic retinopathy, vitreous hemorrhage, and discontinuations of treatment with remigromig. Additional testing is ongoing to describe the results at Merck. The original developer of remigromig, eyed by normal pharmaceutical companies, has not reported any adverse events related to the drug in a Phase 1b/2a trial.
The data will be presented at the American Academy of Ophthalmology Annual Meeting next month by Merck. Big Pharma will also be speaking to regulators about the data. The federal trials database lists another Phase 2b/3 trial of remigromig for DME that is still in progress and expected to complete Primary in March. The second trial, similar to Brunello, is pitting remigromig against ranibizumab.
Market Positioning & Unmet Patient Needs
Mohit Bansal, an analyst at the Wells Fargo event this month, had asked Dean Li, Merck Research Laboratories’ president, if Merck thought it could prove superior to ranibizumab in the Brunello trial. Bansal posed the question within the context of the argument that Merck is “going after the weakest drug.” Lucentis is a contender for the DME market with its competitors Regeneron’s Eylea and Roche’s Vabysmo, which are also drugs targeting VEGF.
At the event, Li explained that 30%-40% of people are unresponsive or fail to respond to current VEGF drugs. Remigromig is Merck’s bid to provide an alternative for those DME patients. In the eye, the company expects ophthalmologists to “mix and match” between VEGF and non-VEGF treatments, Li said, and will hope that’s the case for Merck’s Tie2xVEGF bispecific.
The Tie2xVEGF bispecific (MK-8748) was acquired by Merck in its $1.3 billion upfront purchase of EyeBio in 2024, along with remigromig. Merck also has to pay up to $1.7 billion in milestones. The assets are on Merck’s agenda as it aims to expand beyond the loss of Keytruda’s exclusivity.
Merck has reported encouraging Phase 2b/3 results for remigromig, an investigational treatment for diabetic macular edema (DME). In the 52-week Brunello study involving 984 patients, remigromig met its primary endpoint by demonstrating non-inferiority to ranibizumab for best-corrected visual acuity.
The Science Behind the Eye Disease Program
Diabetic macular edema develops when damaged blood vessels in the retina leak fluid into the macula, the part of the eye responsible for sharp central vision. Persistent swelling can interfere with vision and may lead to progressive visual impairment.
Current treatment approaches commonly focus on reducing vascular leakage through inhibition of vascular endothelial growth factor (VEGF). The investigational approach discussed in the program works differently by targeting the Wnt signaling pathway, which plays a role in retinal vascular stability.
Potential Advantages of a Different Mechanism
A treatment based on Wnt pathway activation could potentially complement or provide an alternative to existing anti-VEGF therapies. The scientific rationale is based on strengthening the blood-retinal barrier and reducing abnormal vascular leakage.
The possibility of using a different mechanism is particularly relevant for patients who require repeated injections or whose response to existing treatments is incomplete. However, additional clinical evidence is needed to establish how the approach compares with currently available therapies.
Clinical Development Remains Important
The reported trial results provide an important milestone, but they are only part of the development process. Researchers will continue examining visual outcomes, anatomical measurements, treatment durability and adverse events across longer follow-up periods.
The ongoing second study is expected to provide additional evidence about efficacy and safety. Regulatory agencies will also assess the complete clinical dataset before determining whether the treatment can be approved.
Merck Plans Further Development
Merck plans to present additional Brunello data at the American Academy of Ophthalmology annual meeting and discuss the results with regulatory authorities
