Merck & Co., Inc. (NYSE: MRK) has presented detailed one-year findings from its pivotal Phase 2b/3 BRUNELLO trial showing that both investigated doses of remigromig achieved the study’s primary non-inferiority endpoint against ranibizumab in adults with diabetic macular edema. The results, presented at the American Academy of Ophthalmology 2026 Annual Meeting in New Orleans on October 10, demonstrated meaningful visual-acuity improvements while revealing higher rates of proliferative diabetic retinopathy-related adverse events and treatment discontinuations in the investigational treatment groups.
The presentation adds numerical efficacy and safety detail to the positive topline results Merck disclosed on September 24, 2026. Both remigromig doses achieved the prespecified statistical threshold for non-inferiority, supporting continued development of a therapy built around activation of the Wingless-related integration site, or Wnt, signalling pathway rather than direct inhibition of vascular endothelial growth factor. However, neither dose established superiority over ranibizumab, and the differences in retinal adverse events create an important challenge for subsequent clinical and regulatory evaluation.
For Merck, BRUNELLO is more than another late-stage ophthalmology study. The results provide pivotal clinical evidence for remigromig, previously designated MK-3000 and EYE103, which entered the company’s portfolio through its 2024 acquisition of EyeBio. The strategic opportunity is to establish a differentiated therapeutic approach in a market dominated by anti-VEGF medicines, but the ultimate value of that differentiation will depend on whether the investigational antibody can deliver a convincing balance of visual benefit, retinal safety and treatment convenience.
How did remigromig perform against ranibizumab in the BRUNELLO one-year results?
The BRUNELLO study enrolled 984 adults with diabetic macular edema and randomly assigned participants in a 1:1:1 ratio to receive remigromig 0.5 mg, remigromig 0.8 mg or ranibizumab 0.5 mg. All three treatment groups received intravitreal injections every four weeks during the first year, providing a controlled comparison of the investigational therapy with an established anti-VEGF treatment. The randomized, double-masked trial evaluated changes in best-corrected visual acuity using standardized Early Treatment Diabetic Retinopathy Study letter scores.
At week 52, patients receiving remigromig 0.5 mg achieved a mean improvement of 9.1 letters from baseline, with a 95% confidence interval of 8.1 to 10.1 letters. The higher 0.8 mg dose produced a mean improvement of 8.7 letters, with a 95% confidence interval of 7.7 to 9.8 letters, while patients receiving ranibizumab gained 11.8 letters, with a corresponding confidence interval of 10.7 to 12.8 letters. Merck reported multiplicity-adjusted non-inferiority p-values of 0.0129 and 0.0222 for the lower and higher remigromig doses, respectively.
The numerical difference between remigromig and ranibizumab was approximately 2.7 letters for the 0.5 mg dose and 3.1 letters for the 0.8 mg dose. Merck reported that these differences remained within the trial’s prespecified non-inferiority margin and were not considered clinically meaningful under the study’s assessment. Importantly, the statistical finding establishes that remigromig satisfied the defined non-inferiority criterion; it does not demonstrate identical efficacy, equivalence across all patient populations or superiority over the comparator.
The absence of superior performance across the reported secondary endpoints further defines the evidence. BRUNELLO assessed superiority in visual-acuity improvement and central subfield thickness, an anatomical measure of retinal swelling, but neither remigromig group demonstrated superiority to ranibizumab on these endpoints. Consequently, the current evidence supports remigromig as a potentially effective alternative mechanism rather than a treatment that has demonstrated better visual or anatomical outcomes than established anti-VEGF therapy.
An additional observation concerns dose selection. The 0.8 mg group did not produce a greater mean visual-acuity improvement than the 0.5 mg group, although the numerical difference between doses alone cannot establish that their efficacy is identical. Merck will need to consider the complete efficacy, exposure and safety evidence when determining the most appropriate dose for potential regulatory submissions.
Why are the higher proliferative diabetic retinopathy-related event rates a critical finding?
The most consequential limitation in the newly presented BRUNELLO results concerns adverse events associated with proliferative diabetic retinopathy, a serious manifestation of diabetic retinal disease involving abnormal blood vessel growth. Merck reported these events in 6.7% of patients receiving remigromig 0.5 mg and 6.1% receiving remigromig 0.8 mg, compared with 0.9% in the ranibizumab group. The absolute differences were 5.8 and 5.2 percentage points, respectively, making the imbalance clinically relevant to evaluate even though the findings do not independently establish a causal relationship with remigromig.
The reported figures are particularly important because Merck’s adverse-event grouping includes several terms indicative of proliferative diabetic retinopathy. These encompass events involving abnormal retinal or iris neovascularization, vitreous hemorrhage and related complications, rather than exclusively cases recorded under one diagnostic term. A complete assessment will require examination of the individual event categories, their severity, timing, baseline disease characteristics and consequences for visual outcomes.
Treatment discontinuations due to adverse events also occurred more frequently with remigromig. Discontinuation rates reached 4.9% in the 0.5 mg group and 4.5% in the 0.8 mg group, compared with 0.9% among patients assigned to ranibizumab. Although these percentages do not establish that the investigational drug directly caused every event, the higher discontinuation burden is relevant when assessing the treatment’s overall benefit-risk profile.
Merck indicated that proliferative diabetic retinopathy cases were generally manageable using established treatments and that additional analyses were underway to characterize the findings. The company also suggested that the observed events could partly reflect the natural progression of diabetic retinal disease, given that remigromig targets retinal barrier restoration rather than directly suppressing abnormal blood vessel formation. That explanation remains a clinical hypothesis requiring further assessment, particularly because the active comparator also influences mechanisms involved in retinal vascular disease.
A randomized trial can reveal clinically important differences between treatment strategies without necessarily proving that one medicine directly causes a specific complication. In this case, the imbalance could involve differences in protection against retinal neovascularization, underlying disease progression, treatment effects or several interacting factors. Understanding these possibilities will be essential before determining whether the findings represent a manageable distinction between mechanisms or a limitation that materially affects the investigational therapy’s clinical positioning.
Can Wnt pathway activation offer a different approach to diabetic macular edema treatment?
Remigromig is an investigational tetravalent, tri-specific antibody designed to activate the Wnt signalling pathway, which participates in maintaining and repairing the blood-retinal barrier. This biological structure helps regulate movement of fluid and other substances between the retinal circulation and surrounding tissue. Damage to the barrier contributes to vascular leakage and fluid accumulation in diabetic macular edema, making restoration of its function a potentially relevant therapeutic strategy.
Existing anti-VEGF medicines primarily work by inhibiting vascular endothelial growth factor, a signalling protein involved in vascular permeability and abnormal blood vessel formation. Their ability to reduce leakage and control neovascular processes has made VEGF inhibition a foundational approach in retinal medicine. Remigromig targets a different biological pathway, seeking to improve retinal vascular integrity through Wnt activation rather than relying on direct VEGF suppression.
The BRUNELLO findings provide important clinical evidence supporting that mechanism because patients receiving remigromig achieved substantial improvements in visual acuity during the first year. The results indicate that Wnt pathway activation can be associated with visual outcomes meeting the trial’s defined non-inferiority standard against an active anti-VEGF comparator. However, the study does not establish that remigromig repairs the blood-retinal barrier more effectively than existing therapies or that the proposed mechanism accounts for every observed clinical benefit.
The distinction between controlling macular edema and preventing proliferative retinal disease may become central to remigromig’s future development. Diabetic macular edema and proliferative diabetic retinopathy are related manifestations of diabetic retinal disease, but their clinical features and therapeutic requirements are not identical. A treatment capable of reducing fluid accumulation and improving vision may still require additional evidence regarding its effects on abnormal vessel growth, retinal hemorrhage and progression of diabetic retinopathy.
This creates a potential question about therapeutic positioning rather than automatically invalidating the Wnt approach. If subsequent studies confirm useful visual benefits but identify differences in protection against proliferative complications, clinical investigators may need to examine which patients are most likely to benefit and whether particular disease characteristics influence outcomes. Such strategies would require appropriate supporting evidence and cannot be inferred from the current non-inferiority result alone.
What does the BRUNELLO trial design establish, and what remains unresolved after 52 weeks?
BRUNELLO’s randomized, double-masked design and active comparator strengthen the interpretability of the reported visual-acuity results. Its 984-participant population provides a substantial controlled evidence base for evaluating treatment effects in adults with diabetic macular edema. The use of standardized visual-acuity testing also supports a clinically relevant assessment, rather than relying exclusively on changes in anatomical measurements or biological markers.
Nevertheless, the published conference-stage findings leave several important questions beyond the successful primary endpoint. Detailed subgroup outcomes, baseline retinopathy severity, prior treatment exposure and the relationship between retinal complications and subsequent visual changes will help establish how consistently the observed effects apply across different patient profiles. Complete reporting of adverse-event categories and treatment exposure will also be important in evaluating the safety differences between groups.
The study’s second year introduces another consequential assessment through a personalized treatment interval algorithm. During the first year, all participants received treatment every four weeks, meaning the current results cannot demonstrate that remigromig reduces injection frequency compared with ranibizumab. Subsequent data may establish whether visual improvement can be maintained with individualized treatment intervals and whether the safety profile changes under a less frequent dosing schedule.
Durability is particularly relevant because diabetic macular edema often requires prolonged management. Initial visual improvement does not necessarily guarantee sustained benefit when dosing intervals are extended, especially if recurrent fluid accumulation or progressive retinal disease affects outcomes. The second-year observations should therefore add evidence about the relationship between treatment frequency, visual stability, anatomical response and complications.
Why would Merck face strong competition even if remigromig eventually secures approval?
An important commercial consideration is that the diabetic macular edema market has continued to evolve beyond the monthly ranibizumab regimen used in BRUNELLO. Longer-acting anti-VEGF therapies and individualized dosing approaches have reduced treatment frequency for some patients, making durability an increasingly important component of clinical differentiation. A new drug demonstrating non-inferior efficacy against monthly ranibizumab would therefore enter a treatment environment where visual outcomes are only one element of the prescribing decision.
Regeneron Pharmaceuticals’ Eylea HD, containing aflibercept 8 mg, provides an example of this evolving treatment landscape. Its United States prescribing information allows dosing every eight to sixteen weeks after initial monthly injections for diabetic macular edema, with further extension to twenty weeks possible in certain patients after successful treatment. These dosing characteristics cannot be directly compared with BRUNELLO efficacy outcomes because the therapies have not been evaluated against each other in the same randomized trial.
Remigromig’s differentiated mechanism could nevertheless offer a potential commercial opportunity if further evidence identifies meaningful clinical advantages in defined treatment settings. Patients with persistent edema, incomplete responses or other unmet needs remain important considerations in retinal drug development. However, BRUNELLO was designed to establish efficacy relative to ranibizumab, not to demonstrate that remigromig improves outcomes specifically in patients who have failed other anti-VEGF therapies.
Commercial adoption would also depend on factors beyond efficacy and safety, including regulatory labeling, physician confidence, product pricing, reimbursement and the resources required for repeated intravitreal administration. Retinal specialists would need to understand whether the therapy provides advantages sufficient to justify changing established treatment protocols. Without an injection-frequency advantage, superior clinical outcome or clearly established benefit in a specific patient population, novelty of mechanism alone may not be enough to produce rapid market uptake.
How does Merck’s EyeBio acquisition influence the strategic importance of remigromig?
Merck acquired EyeBio in July 2024 as part of its strategy to diversify its pharmaceutical development portfolio through opportunities based on differentiated biological mechanisms. The original transaction terms included approximately $1.3 billion in upfront consideration and up to $1.7 billion in contingent development, regulatory and commercial milestone payments, for a maximum potential transaction value of $3 billion. The contingent portion was not guaranteed consideration, and its ultimate payment depends on the achievement of specified milestones.
Remigromig, previously known as Restoret and EYE103, represented EyeBio’s lead clinical candidate at the time of the transaction. Its progression into pivotal development has turned the acquisition into a meaningful test of Merck’s ability to translate externally acquired biotechnology assets into commercially viable medicines. BRUNELLO’s successful primary endpoint provides supporting evidence for the original scientific rationale, although the safety findings illustrate why clinical development risk remains significant even after an efficacy milestone has been achieved.
Merck is also expanding its ophthalmology pipeline through MK-8748, also known as Tiespectus or EYE201, an investigational bispecific antibody combining Tie2 pathway activation with VEGF inhibition. The company reported ongoing pivotal studies investigating this separate candidate in neovascular age-related macular degeneration and diabetic macular edema. Unlike remigromig’s Wnt-focused approach, the MK-8748 programme incorporates direct VEGF inhibition, giving Merck exposure to different mechanisms within retinal vascular disease.
The broader pharmaceutical context also matters. Merck reported worldwide second-quarter 2026 sales of approximately $16.6 billion, including around $8.4 billion from its Keytruda family of cancer treatments, illustrating the company’s continued concentration in major established franchises. Ophthalmology remains a development-stage diversification opportunity rather than a demonstrated near-term replacement for existing revenue streams.
For investors, remigromig should therefore be evaluated as a longer-term clinical and commercial asset. The BRUNELLO results reduce uncertainty surrounding whether its mechanism can achieve the trial’s visual-acuity efficacy objective, but they do not establish regulatory success, market share or future sales. The development’s economic contribution will depend on the outcome of confirmatory evidence, regulatory assessment and the eventual competitive characteristics of any approved product.
Merck shares closed at $145.60 on October 9, 2026, gaining approximately 2.3% during the final trading session before the conference presentation. Because the detailed results were released on Saturday, October 10, that closing movement cannot be interpreted as a market reaction to the newly disclosed numerical findings. The broader stock performance also reflects Merck’s diversified pharmaceutical operations, making it inappropriate to attribute changes in its valuation solely to the ophthalmology programme.
What must the BAROLO study establish before remigromig can advance toward regulatory review?
The next major clinical component for remigromig is the ongoing pivotal Phase 2b/3 BAROLO study, which is also evaluating the investigational antibody in adults with diabetic macular edema. Merck plans to discuss the BRUNELLO findings with regulatory authorities, but it has not announced marketing approval for remigromig. Additional clinical evidence and regulatory agreement will determine the requirements for any future submission.
BAROLO has become particularly important because it can provide further evidence on whether the visual-acuity findings observed in BRUNELLO are reproducible and whether the retinal safety imbalance persists. Consistency across studies would strengthen confidence in the drug’s efficacy profile, while additional safety information could help clarify the clinical significance of proliferative diabetic retinopathy-related events. Differences in patient characteristics, event timing and treatment exposure may also help explain how the observed benefit-risk profile should be interpreted.
Beyond diabetic macular edema, Merck is investigating remigromig in a Phase 2 proof-of-concept study named SUPER TUSCAN involving neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion. These indications involve retinal vascular abnormalities but have distinct disease characteristics and treatment considerations. Positive results in diabetic macular edema cannot be assumed to establish efficacy in either additional condition, and each programme will require indication-specific evidence.
Regulatory assessment will ultimately extend beyond whether BRUNELLO satisfied its primary statistical objective. Authorities will need to consider the magnitude and consistency of visual improvement, the full safety dataset, the comparative characteristics of the treatment and the proposed patient population. Manufacturing controls and the suitability of the final clinical evidence package will also influence the pathway toward any potential marketing authorization.
The results place Merck in an interesting but demanding position within ophthalmology drug development. Remigromig has now produced pivotal evidence that Wnt pathway activation can achieve visual-acuity gains meeting a non-inferiority standard against ranibizumab, supporting a biological approach distinct from conventional VEGF inhibition. Yet the higher rates of proliferative diabetic retinopathy-related adverse events and treatment discontinuations mean that efficacy alone cannot settle its clinical value.
The decisive evidence will come from understanding whether the observed retinal complications represent a persistent difference between treatment approaches and whether longer-term outcomes justify remigromig’s place among established therapies. BAROLO and the continuing BRUNELLO follow-up must provide a sufficiently persuasive account of efficacy, safety and durability to support regulatory consideration. For Merck, the central challenge is no longer simply demonstrating that its Wnt antibody can improve vision, but establishing where that improvement fits within the broader treatment of diabetic retinal disease.
