Merck: BRUNELLO one-year data — remigromig non-inferior to ranibizumab in DME
- BRUNELLO randomized 984 DME patients 1:1:1 to remigromig 0.5 mg, remigromig 0.8 mg, or monthly 0.5 mg ranibizumab.
- Year‑1 mean BCVA gains: +9.1 letters (remigromig 0.5 mg), +8.7 letters (remigromig 0.8 mg) versus +11.8 letters (ranibizumab); both remigromig arms met prespecified non‑inferiority.
- PDR‑related adverse events occurred in 6.7% (0.5 mg) and 6.1% (0.8 mg) with remigromig versus 0.9% with ranibizumab; treatment discontinuations due to AEs were 4.9% and 4.5% versus 0.9%.
- Remigromig is an intravitreal tetravalent, tri‑specific antibody that activates the Wnt pathway; results will be discussed with regulators and BAROLO and other trials are ongoing.
Efficacy results
In the pivotal Phase 2b/3 BRUNELLO trial both remigromig dose arms met the primary endpoint, demonstrating non‑inferiority in mean change from baseline in best‑corrected visual acuity (BCVA) at one year versus monthly 0.5 mg ranibizumab. Mean BCVA gains at Year 1 were +9.1 letters (95% CI, 8.1–10.1; p=0.0129, multiplicity‑adjusted) with remigromig 0.5 mg and +8.7 letters (95% CI, 7.7–9.8; p=0.0222, multiplicity‑adjusted) with remigromig 0.8 mg, compared with +11.8 letters (95% CI, 10.7–12.8) with ranibizumab. Differences were within the prespecified non‑inferiority margin and judged not clinically meaningful. No secondary endpoints showed superiority to ranibizumab.
Safety and tolerability
Adverse events indicative of proliferative diabetic retinopathy (PDR) were reported more frequently with remigromig (6.7% at 0.5 mg; 6.1% at 0.8 mg) than with ranibizumab (0.9%), inclusive of new‑onset PDR. Treatment discontinuations due to adverse events were also higher in the remigromig arms (4.9% and 4.5%) versus 0.9% for ranibizumab. Merck stated PDR cases were generally manageable with standard‑of‑care treatment and additional analyses are underway to characterize these findings; the company noted remigromig targets repair of the blood‑retinal barrier rather than directly suppressing neovascular growth.
Trial design and next steps
BRUNELLO (NCT06571045) randomized 984 adults with DME 1:1:1 to remigromig 0.5 mg, remigromig 0.8 mg or ranibizumab 0.5 mg every four weeks during Year 1; Year 2 treatment frequency will follow a personalized treatment interval algorithm. The primary endpoint was mean change in BCVA to week 52; key secondary endpoints included superiority comparisons for BCVA and central subfield thickness. Results will be discussed with regulatory authorities.
Product and pipeline context
Remigromig (MK‑3000, formerly EYE103) is an investigational intravitreal tetravalent, tri‑specific antibody designed to activate the Wnt pathway and is being evaluated in BRUNELLO, the ongoing BAROLO Phase 2b/3 study, and a Phase 2 proof‑of‑concept study in NVAMD and RVO (SUPER TUSCAN). Merck is also developing MK‑8748 (Tiespectus, EYE201), a bispecific Tie2 activator/VEGF inhibitor, in pivotal trials for NVAMD (TORRONTES, MALBEC) and DME (SANGIOVESE, SYRAH).
Source: Merck