Merck's remigromig meets primary endpoint in BRUNELLO Phase 2b/3 DME trial
- Both remigromig doses (0.5 mg and 0.8 mg) met the primary endpoint of non-inferiority to 0.5 mg ranibizumab for mean BCVA change at week 52.
- BRUNELLO enrolled 984 participants randomized 1:1:1 to low-dose remigromig, high-dose remigromig or ranibizumab, treated every four weeks in year one.
- Higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage and treatment discontinuations due to adverse events were reported in remigromig arms versus ranibizumab.
- Year-one BRUNELLO results will be presented at the AAO Annual Meeting on Oct. 10 and will be discussed with regulatory authorities; remigromig is also in BAROLO and SUPER TUSCAN studies.
Topline efficacy
In the pivotal Phase 2b/3 BRUNELLO trial, both 0.5 mg and 0.8 mg doses of remigromig (MK-3000) independently demonstrated non-inferiority to active control 0.5 mg ranibizumab for mean change from baseline in best-corrected visual acuity (BCVA) at week 52 in adults with diabetic macular edema (DME).
Safety findings
While both doses were described as generally well tolerated, higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage and treatment discontinuations due to adverse events were observed in the remigromig treatment arms compared with ranibizumab; further analyses are underway to characterize these findings.
Trial design and next steps
BRUNELLO randomized 984 participants 1:1:1 to low- and high-dose remigromig or ranibizumab, with dosing every four weeks in year one and a shift to a personalized treatment interval algorithm in year two. The year-one results will be presented at the American Academy of Ophthalmology Annual Meeting on Oct. 10 and will be discussed with regulatory authorities. BRUNELLO is the first of two pivotal Phase 2b/3 trials evaluating remigromig; BAROLO is ongoing and a Phase 2 proof-of-concept trial (SUPER TUSCAN) is under way in NVAMD and RVO.
Product profile and pipeline context
Remigromig is an investigational tetravalent, tri-specific antibody designed to activate the Wnt pathway to support repair and maintenance of the blood–retinal barrier and is administered by intravitreal injection. Merck also highlighted MK-8748 (Tiespectus), a bispecific Tie2 activator/VEGF inhibitor, which is in pivotal studies for NVAMD and in Phase 3 trials for DME.
Source: Merck